Introduction

Within the spinal column lies the spinal cord, a vital aspect of the central nervous system (CNS). The three primary roles of the spinal cord are to send motor commands from the brain to the body, send sensory information from the body to the brain, and coordinate reflexes. The spinal cordis organized segmentally, with thirty-one pairs of spinal nerves emanating from it. A spinal cord injury disrupts this conduit between the body and brain and canlead to deficits in sensation, movement, and autonomic regulation, as well as death.

The spinal cord is composed of gray and white matter, appearing in a cross-section as H-shaped gray matter surrounded by white matter. The gray matter consists of the cell bodies of motor and sensory neurons, interneurons,and neuropils (neuroglia cells and mostly unmyelinated axons). In contrast, the white matter is composed of interconnecting fiber tracts, which are primarily myelinated sensory and motor axons. The supports of the gray matters H make up the right dorsal, right ventral, left dorsal, and left ventral horns. Running longitudinally through the center of the spinal cord is the central canal, which is continuous with the brains ventricles and filled with cerebrospinal fluid (CSF).

The white matteris organized into tracts. Ascending tracts carry information from the sensory receptors to higher levels of the CNS, while descending tracts carry information from theCNS to the periphery. The major tracts and their most defining features are as follows:[1]

Ascending Tracts

Dorsal column: contains the gracile fasciculus and cuneate fasciculus, which togetherform the dorsal funiculus. The dorsal column is responsible for pressure and vibration sensation, two-point discrimination, movement sense, and conscious proprioception. The dorsal column decussates at the superior portion of the medulla oblongata and forms the medial lemniscus.

Lateral spinothalamic: carries pain and temperature information. The lateral spinothalamic tract decussates at the anterior commissure, two segments above the entry to the spinal cord.

Descending Tracts

Lateral and anterior corticospinal: involved in conscious control of the skeletal muscle. The majority of lateral corticospinal tract fibers decussate at the inferior portion of the medulla oblongata, while anterior corticospinal descends ipsilaterally in the spinal cord and decussates at the segmental level. The lateral corticospinal tract, also called the pyramidal tract, innervates primarily contralateralmuscles of the limbs, while the anterior corticospinal tract innervates proximal muscles of the trunk.

Vestibulospinal: carries information from the inner ear to control head positioning and is involved in modifying muscle tone to maintain posture and balance. The vestibulospinal tract does not decussate.

Rubrospinal: involved in the movement of the flexor and extensor muscles.The rubrospinal tract originates from the red nuclei in the midbrain and decussates at the start of its pathway.

There is a laminar distribution of neurons in the gray matter, characterized by density and topography:

Lamina II is composed mainly of islet cells with rostrocaudal axes, which contain GABA and are thought to be inhibitory, and stalked cells with dorsoventral dendritic trees.

Lamina V and VI are composed of medium-sized multipolar neurons that can be fusiform or triangular. These neurons communicate with the reticular formation of the brainstem.

Lamina VII is composed of homogenous medium-sized multipolar neurons and contains, in individual segments, well-defined nuclei, including the intermediolateral nucleus (T1-L1), which has autonomic functions, and the dorsal nucleus of Clarke (T1-L2), which make up the dorsal spinocerebellar tract.

Lamina VIII consists of neurons with dorsoventrally polarized dendritic trees.

Lamina IX has the cell bodies of motor neurons, with dendrites extending dorsally into laminas as far as VI. Lamina IX also has Renshaw cells, inhibitory interneurons, placed at the medial border of motor nuclei.

Neurulation begins in the trilaminar embryo when part of the mesoderm differentiates into the notochord. The formation of the notochord signals the overlying ectoderm to form the neural plate, the first structure that will become the nervous system. The neural plate folds in on itself, creating the neural tube, initially open at both ends and ultimately closed. From the neural tube comes the primitive brain and spinal cord.[9]The development of the nervous system begins seventeen days after gestation, and in the fifth week, myotomes start to form, allowing the development of rudimentary reflex circuitries. Myelination of the motor tracts begins in the first few months of life and continues into adolescence.

An interesting note is that reciprocal excitation changes to inhibition between nine and twelve months of age. Before that age, supraspinal descending fibers activate interneurons, resulting in extension or flexion. During this period of development, glycine and GABA are excitatory.[10]

The spinal cord is the conduit between the brain and the rest of the body. It sends motor commands from the motor cortex to the muscles of the body and sensory information from the afferent fibers to the sensory cortex. Additionally, the spinal cord can act without signals from the brain in certain instances. The spinal cord independently coordinates reflexes using reflex arcs.Reflex arcs allow the body to respond to sensory information without waiting for input from the brain. The reflex arc starts with a signal from a sensory receptor, which is carried to the spinal cord via a sensory nerve fiber, synapsed on an interneuron, carried over to the motor neuron, which stimulates an effector muscle or organ.[11]The spinal cord also has central pattern generators, which are interneurons that form the neural circuits, which control rhythmic movements. Although the existence of central pattern generators in humans is controversial, the lumbar spinal cord produces rhythmic muscle activation without volitional motor control or step-specific sensory feedback, suggesting their role in human movement.[12]

Three connective tissue layers,termed meninges, conceal the spinal cord. Directly lining the spinal cord is the pia mater, which also thickens to form the denticulate ligament, anchoring the spinal cord in the middle of the vertebral canal. The next layer of meninges is the arachnoid mater.Between the pia mater and arachnoid mater is the subarachnoid space, which contains CSF. On top of the arachnoid mater is the last layer of meninges, the dura mater, then the epidural space separating the meninges from the vertebral column.[13]

The spinal cord extends from the medulla oblongata of the brain stem at the level of the foramen magnum. In an adult human, the spinal cord gives rise to thirty-one pairs of spinal nerves, each of which originates from the adjacent spinal cord segment:

Spinal nerves emerge from the spinal cord as rootlets, whichjoin together to form two nerve roots.The anterior nerve roots contain motor fibers extending from the anterior horn to peripheral target organs. The motor neurons are multipolar, with at least two dendrites, a single axon, and one or more collateral branches. They control skeletal muscles and the autonomic nervous system. The posterior nerve roots contain sensory fibers and dorsal root ganglia. They contain sensory fibers transmitting sensory information from the periphery towards the CNS. The sensory neurons located at the dorsal root ganglia are pseudounipolar. The anterior and posterior nerve roots converge into spinal nerves, which split into dorsal and ventral rami.A dermatome is a skin area innervated by a single spinal nerve root (or spinal cord segment).

There are five spinal plexuses, which include sensory and motor nerves from the anterior rami:

Cervical plexus (C1-C5): the deep branches innervate neck muscles, and the superficial branches innervate the skin on the neck, head, and chest. The cranial plexus also has an autonomic function, including controlling the diaphragm and interactions with the vagus nerve.

Brachial (C5-T1): controls movement and sensation of the upper extremity.

Lumbar (L1-L4): controls movement and sensation of the abdominal wall, thigh, and external genitals.

Sacral (L4, L5, S1-S4): controls movement and sensation of the foot, leg, and thigh.

Coccygeal (S4, S5, Co): innervates the skin around the tailbone.

In adults, the spinal cord tapers to an end, termed the conus medullaris, at the second lumbar vertebra level. Past the conus medullaris, a bundle of spinal roots extends termed the cauda equina. The cauda equina and the subarachnoid space continue until S2 and is the target location for a lumbar puncture (spinal tap).

Electrophysiological Testing

Evoked potentials (EPs) measure electrical signals going to the brain and can determine whether there is motor or somatosensory impairment. The signal is detected by electroencephalography (EEG) or electromyography (EMG). Evoked potentialsmay be used to assess spinal cord damage in the setting of spinal cord injury and tumors, and measure functional impairment and predict disease progression in multiple sclerosis.[15]Somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs)are frequentlyused intra-operatively for monitoring and can be used post-operatively as surrogate endpoints to check muscle strength and sensory status.[16]

Nerve conduction studies determine whether there has been an injury to a spinal nerve root, peripheral nerve, neuromuscular junction, muscle, cranial nerve, or spinal nerve. They can also be used to pinpoint spinal cord lesions.Nerve conduction studies work by stimulating nerves close to the skin or using a needle placed near a nerve or nerve root. Neurologists often use them with needle electromyograms.[17]

Lumbar Puncture

A lumbar puncture, or spinal tap, samples the CSF from the subarachnoid space. The needle to obtain the sample should be inserted between lumbar spinal canal levels L3 and L4 to avoid contact with the spinal cord.[18]TheCSF is then sent to a laboratory to establish whether any insult can be determined.For instance, a lumbar puncture can confirm or exclude bacterial meningitis, which will produce a cloudy fluid suggestive of a high leukocyte count. It is also important to know when not to use a lumbar puncture. Contraindications to lumbar puncture include signs of cerebral herniation, focal neurological signs, uncorrected coagulopathies, or cardiorespiratory compromise.[19]

Deep Tendon Testing

One aspect of theneurological exam is a test of the deep tendon reflexes, which are involuntary motor responses to various stimuli that function via reflex arcs within the spinal cord. They can be used to test the function of the motor and sensory nerves at specific spinal cord levels.Reflex grading is on a scale of 0 (absent reflex) to 5+ (sustained clonus).[20]Some commonly tested reflexes are as follows:

Additionally, the Babinski reflex, or the extensor plantar reflex, can be seen in newborns but is an abnormal response aftersix to twelve months of age. If the Babinski reflex is seen after 12 months of age, it may indicate an abnormality in the corticospinal system.[21]

Spinal Cord Injury

Primary spinal cord injury occurs due to local deformation of the spine, such as direct compression. Secondary spinal cord injury occurs following primary damage and involves cascades of biochemical and cellular processes, including electrolyte disturbances, free radical damage, edema, ischemia, and inflammation.[22]Secondary spinal cord injury has several phases: acute, subacute, and chronic. During the acute phase (up to 48 hours after the primary injury), hemorrhage and ischemia lead to ion balance disruption, excitotoxicity, and inflammation. During the subacute phase (up to two weeks following primary injury), there is a phagocytic response and a reactive proliferation of astrocytes, which leads to a glial scar in the chronic phase. The thinking is that scarification is the critical component to permanent disability because it prevents axonal regeneration; axons otherwise could regenerate, but their growth is blocked. However, that notion has been subject to challenge, and there are suggestions that astrocyte scar formation could aid in regeneration.[23]In the chronic phase (over six months after the primary injury), the scarification process is complete.[24]

Developmental

Open neural tube defects occur when there is a failure of the neural tube to close. If it fails to close at the cranial end, the fetusmay develop anencephaly. If the failure is at the caudal end, the fetusmay have myelomeningocele or open spina bifida. Craniorachischisis can also occur if the entire neural tube remains open. Closed neural tube defects are spinal cord development problems that are skin-covered, such as occult spina bifida.Folic acid supplements lower the risk of neural tube defects, although severe folate deficiency in mouse models does not lead to neural tube defects unless there is already a genetic predisposition. Suggestions are that folate can overcome a genetic predispositionfor adverse effects, potentially leading to neural tube defects.[25]

A spinal cord injury can be classified as complete or incomplete. A complete injury, based on the International Standard Neurological Classification of Spinal Cord Injury (ISNCSCI) examination, developed by the American Spinal Cord Injury Association (ASIA), implies that there is no sensation at the inferior segments of the spinal cord (S4-S5); no deep anal pressure (DAP) or voluntary anal contraction (VAC) is present. If no perianal sensation is present and DAP and VAC are absent, the present function below the level of injury is a zone of partial preservation.[26]

An injury in the cervical region often results in quadriplegia if both sides of the spinal cord are affected and hemiplegia if only one side is affected. Nerves from C3, C4, and C5 stimulate the phrenic nerve, which controls the diaphragm, so injury to C4 and above may result in a permanent need for a ventilator. An injury to the thoracic region often limits the function of nerves related to the lower torso and lower extremities. Usually, it does not affect the upper torso and upper extremities, except in rare cases such as subacute posttraumatic ascending myelopathy (SPAM).[27]Injury to thespinal cord often causes loss of bowel and bladder control, loss of sexual function, and blood pressure dysregulation, as the spinal cordrelays autonomic and somatic information.

Syndromes

Several syndromes correlate with spinal cord injury. Central cord syndrome usually occurs in individuals who suffer a hyperextension injury, and it often leads to incomplete injury with weakness predominantly affecting the upper limbs. The reason for this phenomenon is the organization of the fibers in the spinal cord: the fibers running to the lower extremities are longer than those running to the upper extremities; the longer fibers are located more laterally in the spinal cord (L-L rule). As the central portion of the spinal cord is injured, there is a sparing of the fibers running to the lower extremities. Brown-Sequard syndrome is due to a spinal cord hemisection,leading to a complete loss of sensation at the level of the lesion, as well as deficits below the lesion loss of proprioception, vibration, and motor control, ipsilaterally, and a loss of pain and temperature sensation, contralaterally. Anterior cord syndrome is due to a compromised blood supply to the anterior two-thirds of the spinal cord, damaging the corticospinal and spinothalamic tracts.This syndrome is associated with several deficits at and below the lesion, including motor loss and a loss of pain and temperature sensation. However, light touch and joint position sense from the dorsal columns are left intact.[26]Injury to T12-L2 segmentsmay result in conus medullaris syndrome, while injury to L3-L5 segmentscan lead to cauda equina syndrome. Usually, these syndromes present as incomplete injuries and result in neurogenic bladder and/or bowel, loss of sexual function, and perianal loss of sensation.[28]

See more here:
Physiology, Spinal Cord - StatPearls - NCBI Bookshelf

Dr. Jeff Hersh| Daily News Correspondent

Q: What is CAR T-cell therapy?

A: Our immune system protects our bodies from "invasion"by harmful substances, infections and abnormal cells (for example cancer cells). T-cells (also called T-lymphocytes or thymocytes) develop from stem cells in the bone marrow and mature in the thymus (a body organ in the neck that is part of the lymphoid system, along with the spleen, lymph nodes and the red bone marrow).

Cytotoxic T-cells identify body cells that have certain antigens (proteins on the surface of certain cancer cells, cells that have become infected, other cells) and directly kill them.

Helper T-cells detect various "invasions"and release cytokines to activate other immune system cells (including cytotoxic T-cells) to combat them.

Regulatory T-cells help moderate the immune response to maintain balance and the bodys ability to tolerate (rather than attack) itself (for example helping minimize inappropriate inflammatory responses).

This description of T-cells shows why it would be helpful to "manipulate"them in a specific manner to leverage the immune system to help fight certain diseases/conditions. This is where chimeric antigen receptor (CAR) T-cells come into play.

White blood cells (including T-cells) are collected from the patient by taking some of their blood via an intravenous (IV) catheter and filtering out the white cells using a leukapheresis machine, and then putting the filtered blood (minus the extracted white blood cells) back into the patient via a second IV catheter.

The T-cells are then separated from the other white blood cells, and a gene for the "targeted" antigen is added to the cells (you can think of this as a "lock and key"mechanism, with the antigen being the "lock"and the protein added to the T-cell being the "key"used to identify the "invading" cell with that particular antigen "lock."

These modified cells (the CAR T-cells) are then "multiplied"in the lab to create a large number of them. The CAR T-cells are then infused into the patient (again via an IV). These CAR T-cells can now specifically "hunt"the specific "invading"cell(s) they have been created to target.

There are many steps needed to create this personalized CAR T-cell treatment for an individual patient, and therefore it can take weeks to produce these treatments. In the future it may be possible to pre-prepare treatments from donor T-cells (possibly modifying these cells to target specific antigens using techniques like CRISPR, mRNA techniques, etc.) and then transfuse the appropriate CAR T-cells in a manner similar to how other blood products (for example red cells, platelets, etc.) are transfused to help a patient.

Since 2017 CAR T-cells have been specifically designed and utilized to treat individual patients with several different types of "blood cancers"(lymphomas, leukemias and multiple myelomas) that did not respond to the standard treatments (for example chemotherapy for that type of cancer).In many patients with very difficult to treat blood cancers, these treatments have been very effective.

Solid tumors (as opposed to blood cancers), such as brain, breast, lung and pancreatic cancers, are a bit more challenging to address with the CAR T-cell approach.This is because having the CAR T-cells gain "access"to the solid tumor cancer cells is more difficult.

From the description of T-cells above, it seems that this same conceptual approach might be utilized to treat certain autoimmune conditions (conditions where a patients own immune system "overreacts"and attacks the patients own body cells), and this has recently been studied. In this study, five patients with severe lupus who had not responded to standard treatments were treated with specifically designed CAR T-cells to "wipe out"the aberrant B cells causing their autoimmune complications, and all five showed very significant improvement. Future clinical studies will no doubt be designed to see what other conditions might benefit from this treatment approach!

However, treatment with CAR T-cells is not without risk, as these treatments can sometimes cause serious and even life-threatening complications. For example, some patients have had:

Cytokine release syndrome (CRS), where the patient reacts to the CAR T-cell infusion with an aggressive release of cytokines that causes an inflammatory reaction (for example causing symptoms like fever, breathing issues, gastrointestinal issues, other symptoms); nervous system issues (for example headaches, seizures, alterations in consciousness, others), and there may bemany other possible complications.

Bottom line: CAR T-cell therapy has become a more and more accepted therapeutic approach, and in the future it may be utilized earlier in a patients disease (rather than only for refractory cases), and for a broader array of disease states (not just blood cancers, but potentially autoimmune conditions, maybe certain solid tumors, and potentially other diseases).

Jeff Hersh, Ph.D., M.D., can be reached at DrHersh@juno.com.

Read the original:
CAR T-cell therapy is new approach to fighting cancer, other diseases - MetroWest Daily News

NEW YORK, Oct. 4, 2022 /PRNewswire/ --

Growing Use of IVF and Stem Cell Therapies to Create US$ 323 Million Market Opportunity for Carbon Dioxide Incubator Manufacturers

The carbon dioxide incubators market is well covered by Fact.MR for the upcoming decade. The study looks closely at key growth factors such trends, future projections, and business strategies. The research also provides a thorough analysis of the top segments including product, application, capacity, and region, in order to provide well-rounded perspective.

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Fact.MR A Market Research and Competitive Intelligence Provider: The global carbon dioxide incubators market is likely to reach US$ 483.5 Million by 2027, growing at 8.4% CAGR between 2022 and 2027. Growing investment in research and clinical trial activities is likely to fuel the sales of carbon dioxide incubators during the assessment period. Further, use of carbon dioxide incubators in IVF and stem cell treatments is also likely to drive growth.

The popularity and acceptance of in-vitro fertilizations has grown significantly. According toNational Library of Medicine, around 10% to 15% couples in the U.S. have trouble in having a baby. These challenges have been well-addressed by in vitro fertilization (IVF), owing to which it has become a popular healthcare solution.

Use of in-vitro fertilization (IVF) to help couples in becoming parents is likely to grow in the future, which is likely to drive demand for accessories and equipment used in this process. Owing to this, demand for carbon dioxide incubators is likely to witness an upward trend over the upcoming decade.

Further, sales of carbon dioxide incubators are also likely to increase on account of growth in overall stem cell procedures. For instance, as perHealth Resources and Services Administration, 4,864 unrelated and 4,160 related bone marrow and cold transplants were conducted in the U.S. in 2020. Growing use of stem cell treatment is likely to be a key factor driving the sales of carbon dioxide incubators during the assessment period.

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Globally, North America and Europe are likely to remain at the pinnacle of growth in the carbon dioxide incubators market. The U.S., U.K., France, and Germany are at the forefront of new innovation in R&D, and sales of medical accessories and equipment will also remain high, as per Fact.MR. Owing to these factors, carbon dioxide incubator manufacturers are likely to witness incremental growth opportunities across these regions.

Key Takeaways:

By product, water-jacketed carbon dioxide incubators are likely to reman preferred among end-users.

By capacity, below 100-liter carbon dioxide incubators are expected to witness high demand during the assessment period.

By application, use of carbon dioxide incubators in laboratory research and clinical applications is likely to remain high during the assessment period.

By region, North America and Europe are likely to hold sway over the forecast period, with the U.S. and the U.K. leading the growth.

China and India are expected to create sizeable opportunities for market players on the back of improved healthcare infrastructure.

Growth Drivers:

Increasing applications of carbon dioxide incubators in in-vitro fertilization (IVF) and stem cell treatment is likely to drive the market.

Use of carbon dioxide incubators in cell culture development and tissue engineering is expected to create growth avenues for market players.

Efficiency of incubators in maintaining consistent temperature during genetically modified organism (GMO) cultivation is expected to drive growth.

Advancement in carbon dioxide incubator technology is likely to create new growth avenues for market players.

Restraints:

Carbon dioxide incubators are highly prone to errors due to which they require highly experienced technicians. Due to skill shortage, sales of these incubators can be limited.

Lack of standardization is a longstanding challenge and failure to address this issue might hamper growth.

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Competitive Landscape:

Carbon dioxide incubator manufacturers are focusing on launching innovative technologies to consolidate their position in the market. Further, leading players are concentrating on providing training and guidelines to end-users so their products can be used without any issue.

For instance,

In May 2021, Esco introduced an innovative incubator featuring High Heat Sterilization that is highly effective in eliminating bacteria and vegetative cells.

In January 2020, CO2Meter Inc., launched incubators that regulate and monitor bacterial development patterns.

Key Companies Profiled by Fact.MR

More Valuable Insights on Carbon Dioxide Incubators Market

In its latest study, Fact.MR offers a detailed analysis of the global carbon dioxide incubators market for the forecast period of 2022 to 2027. This study also divulges key drivers and trends promoting the sales of carbon dioxide incubators through detailed segmentation as follows:

By Product:

Water Jacketed

Air Jacketed

Direct Heat

By Capacity:

Below 100 Litres

100-200 Litres

Above 200 Litres

By Application:

By Region:

North America

Latin America

Europe

East Asia

South Asia & Oceania

MEA

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Key Questions Covered in the Carbon Dioxide Incubators Market Report

What is the estimated market size of carbon dioxide incubators in 2022?

At what pace will worldwide carbon dioxide incubators sales increase till 2027?

What factors are driving demand in the carbon dioxide incubators market?

Which region is predicted to lead the worldwide carbon dioxide incubators market between 2022 and 2027?

What are the elements driving carbon dioxide incubators market sales during the forecast period?

What is the expected market estimation of the carbon dioxide incubators market during the forecast period?

Explore Fact.MR's Coverage on the Healthcare Domain

Biological Indicator Incubator Market:The biological indicator incubators market is projected to benefit from rising biopharmaceutical production. The market for biological indicator incubators may continue to increase quickly as a result of the manufacturing of biopharmaceuticals that are grown via cell culture.

Tissue Culture Incubator Market:The introduction of CO2 incubators with infrared radiation control systems and other technological advancements in tissue culture incubators, along with increased funding for tissue-based research, are anticipated to be major factors driving the growth of the tissue culture incubator market over the forecast period.

Pneumatic Nebulizers Market:Pneumatic nebulizer sales are anticipated to grow steadily at a CAGR of 4% and reach a market value of US$ 850.4 million by 2027 from US$ 699 million in 2022. An increase in local healthcare spending and patient awareness has spurred the need for pneumatic nebulizers.

Implantable Medical Devices Market: The global implantable medical devices market is predicted to reach US$ 155 billion by 2027. Key factors driving market growth include rising geriatric population & burden of chronic diseases and increasing demand for cosmetic dentistry.

Disinfection Caps Market: Key factors driving market growth include stringent regulations for safe injection practices and rising prevalence of hospital-acquired infections across the world. The global disinfection caps market is estimated to reach US$ 420 million by 2027.

Check it Out More Reports by Fact.MR on Healthcare Domain

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View original content:https://www.prnewswire.com/news-releases/carbon-dioxide-incubators-market-to-reach-us-483-5-million-by-2027-as-application-in-in-vitro-fertilization-rises-301640474.html

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Carbon Dioxide Incubators Market to Reach US$ 483.5 Million by 2027 as Application in In Vitro Fertilization Rises - Yahoo Finance

Inflammatory bowel disease (IBD) is increasing around the world. In 1990, around 3.7 million people had the condition; by 2017, that number had increased to 6.8 million. Nearly half of IBD patients dont respond to current treatments, and even for the lucky ones therapeutic efficacy can wane over time. As a result, there is an urgent need to develop a new generation of IBD therapies.

Unfortunately, ineffective drug development models are hampering the search for more effective treatments. Conventional two-dimensional (2D) cell models only capture bits and pieces of IBDs complexity, and many three-dimensional (3D) culture models like organoids fall short because they lack critical biological features, such as vasculature and biomechanical forces.

Animal models have their own drawbacks, as their immune systems fail to replicate many of the mechanisms associated with human immunity.

If you look at the physiology of cardiac muscle or neurons between humans and mice, theyre fairly similar, said Christopher Carman, PhD, director of Immunology at Emulate. Theres more divergence in immunology, and it can be really challenging to extract meaningful insights around immune-system-driven mechanisms. Thats why so many therapeutics fail.

To remedy this, Emulate has developed a Colon Intestine-Chip that combines primary human tissue, vasculature, mechanical forces, and (most importantly) immune cell recruitment to recapitulate the biology that drives IBD.

UNDERSTANDING HOW IBD EVOLVES

IBD begins with an unknown tissue insult, and the body responds by producing inflammatory cytokines and chemokines. In turn, these proteins recruit immune cells to the intestine, inducing further inflammation.

This process generates a cytokine cascade. Two proteins in particular, interferon gamma (IFN) and IL-22, act directly on colon epithelial cells, driving cell death, microvilli loss, and destruction of the tight junctions that guard intestinal permeability.

That is a critical hallmark of this disease, said Carman. As a result, intestinal material, including bacteria and bacterial products, leak into the interstitial space, driving even more inflammation.

MAKING THE COLON INTESTINE-CHIP

The Emulate Colon Intestine-Chip was designed to precisely recapitulate this inflammatory cascade.

This advanced, in vitro intestine model incorporates primary human biopsy tissue cultured into organoids. Critically, the cells retain their stemness, meaning they replicate the stem cell niches that are constantly regenerating in human intestines.

After the organoids are dissociated, they are seeded in the top channel of the Organ-Chip. The bottom channel contains primary human intestine-derived microvascular endothelial cells, which are in close proximity to the epithelial cells, as they would be in vivo. The channels are separated by a porous membrane coated with tissue-relevant extracellular matrix proteins.

From there, mechanical forces on the chipphysiologic flow and cyclic stretchreplicate intestinal peristalsis, which improves cell morphology and functionality while supporting more accurate gene expression.

As a result, epithelial tissues respond to microvasculature cues, and the epithelial cells differentiate into all three major epithelial types at the appropriate ratios.

With this, the Emulate Colon Intestine-Chip is able to model IBD from the initial insult to the cytokine cascade, demonstrating along the way selective immune cell recruitment, cell death, and tight junction loss. This model can be applied to study inflammation-specific immune recruitment from vasculature into epithelial tissue and subsequent downstream impacts.

We have shown that this Organ-Chip strongly reflects what we see in primary human tissue, said Carman. It develops proper tight junctions and a strong functional barrier. On the molecular level, we see transcriptional signatures that are highly reflective of primary human tissue.

This model has demonstrated the efficacy of small molecule inhibitors that target IFN and IL-22 signaling pathways, meaning researchers can use it to validate clinically relevant drug candidates designed to prevent barrier dysfunction.

SELECTIVELY GENERATING INFLAMMATION

One of the Organ-Chips most important abilities is the selective recruitment of immune cells. This selectivity comes from tissue-specific adhesion molecules on both endothelial and immune cells, which must be highly specific to bind.

Around 30% of the bodys circulating immune cells are customized for work in the intestines. They have a molecule called 47 integrin that binds to an endothelial molecule called MAdCAM-1, which is preferentially expressed in the colon endothelium and up-regulated in response to inflammatory cues.

One of the major ways the Colon Intestine-Chip replicates IBD biology is by expressing MAdCAM-1 in response to inflammatory stimuli, giving it tremendous relevance for therapeutic discovery.

The 47 integrin/MAdCAM-1 adhesion molecule axis is an important therapeutic target, said Carman. If we can interfere with that adhesion, we can potentially interrupt the inflammatory cascade. And because this mechanism is selective to the gut, any therapeutic that targets these adhesion molecules would be highly specific to the intestinal system.

One drug, AJM300, is in phase three clinical trials right now and is showing promising safety and efficacy, said Carman. We validated that efficacy in our model. We also used the model to study the corticosteroid dexamethasone, which has been a mainstay in IBD treatment for many years. We recently published the data in an application note.

The Colon Intestine-Chip provides a more complete picture of human IBD pathogenesis, delivering a human-relevant platform to test drug efficacy. However, for Emulate, its just the beginning. Inflammation plays a major role in many conditions, and creating models that effectively replicate those pathways will be essential in validating and advancing therapeutic compounds to support better care.

This IBD model is our first foray into inflammation, said Carman. Were planning on developing many variations on this theme to create better tools for a variety of inflammation-driven indications.

For more information on Emulates IBD model, please download Modeling Inflammation-Specific Immune Cell Recruitment in the Colon Intestine-Chip.

Read more from the original source:
Recapitulating Inflammation: How to Use the Colon Intestine-Chip to Study Complex Mechanisms of IBD - Pharmaceutical Executive

Visiongain has published a new report entitled Mesenchymal Stem Cells Market 2022-2032. It includes profiles of Mesenchymal Stem Cells Market and Forecasts Market Segment by Type {Product (Cell & Cell Lines, Kits Media & Reagents, Others), Services}, Market segment by Source (Bone Marrow, Adipose Tissue, Cord Blood, fallopian Tube, Fetal Liver, Lung, Peripheral Blood, Other Sources), Market Segment by Indication (Bone & Cartilage Repair, cardiovascular Disease, Cancer, GvHD, Inflammatory & Immunological Diseases, Liver Diseases, Other Diseases), Market Segment by Application (Disease Modelling, Drug Discovery & Development, Stem Cell Banking, Tissue Engineering, Toxicology Studies, Other Applications) plus COVID-19 Impact Analysis and Recovery Pattern Analysis (V-shaped, W-shaped, U-shaped, L-shaped), Profiles of Leading Companies, Region and Country.

The mesenchymal stem cells market was valued at US$2.44 billion in 2021 and is projected to grow at a CAGR of 13.82% during the forecast period 2022-2032.

Rising Awareness About Therapeutic Potential of Mesenchymal Stem CellsThe mesenchymal stem cell (MSC) market has a huge potential for expansion as it's the most prevalent stem cell type used in regenerative medicine. MSCs are now the most commonly used stem cell type in clinical trials and the most researched stem cell type in the scientific literature. MSC-based therapies are also gaining popularity due to the rapidly aging population and rising prevalence of chronic diseases. Mesenchymal Stem cells play a significant role in effective management of disease and research initiatives in specialized areas such as genomic testing and personalized medicine. As a result of rising awareness of the therapeutic potential of stem cells and the scarcity of effective therapeutic treatments for rare diseases there is rise in investment leading to the growth of the market, however significant operational cost associated with the mesenchymal stem cell expansion and banking is anticipated to hinder the market growth.

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Mesenchymal Stem Cells Market Report 2022-2032

How has COVID-19 had a Significant Negative Impact on the Mesenchymal Stem Cells Market?

The biotechnology industry has experienced evolutionary changes with regards to the operational management. Typical biopharmaceutical companies manufacturing products for mesenchymal stem cell development had a better response to staff disruptions and challenges evolving due to COVID-19.

There was an impact on the research & development activities and clinical trials as there were interruptions in the new patient enrolment for the active clinical trial. However, the business focused on inventing new therapies for the treatment of COVID-19 disease. In the past years, MSCs have established itself to be an effective technique to treat pulmonary disease, including COVID-19. MSC derived stem cell therapies have showed the potential for the treatment of the Covid 19 disease. Therefore, an increase in the number of clinical trials using MSCs has been observed. Countries such as the US, the UK, Belgium, France, Spain and Mexico are conducting clinical trials with mesenchymal stem cells to be used in the treatment of COVID-19.

How will this Report Benefit you?

Visiongains 281-page report provides 117 tables and 184 charts/graphs. Our new study is suitable for anyone requiring commercial, in-depth analyses for the mesenchymal stem cells market, along with detailed segment analysis in the market. Our new study will help you evaluate the overall global and regional market for Mesenchymal Stem Cells Market. Get financial analysis of the overall market and different segments including type, Source, Indication, Application, and company size and capture higher market share. We believe that there are strong opportunities in this fast-growing mesenchymal stem cells market. See how to use the existing and upcoming opportunities in this market to gain revenue benefits in the near future. Moreover, the report will help you to improve your strategic decision-making, allowing you to frame growth strategies, reinforce the analysis of other market players, and maximise the productivity of the company.

What are the Current Market Drivers?

MSCs in the Development of Engineered Tissues and OrganshMSCs are considered as one of the prominent bio fabrication materials for decades as they are proved safe and effective in treating various injuries and diseases such as bone or cartilage regeneration, stroke & cancer. Bioprinting is a rapidly expanding tissue engineering area with a lot of promise for product customization and addressing the global tissue and organ scarcity, with a global market of $1.82 billion USD predicted by 2022. hMSCs have also been found to be capable of being guided toward hepatocyte differentiation thus indicating huge demand for hMSCs as tissue engineering of organ develops. The requirement for hMSC in engineered tissue and organ applications is, of course, reliant on cell generation, differentiation, and maturation technologies for the parenchymal cells required for organ function and thus it is expected that the increased availability of hMSC sources as a result of manufacturing technology advancements will pave the way for quick improvement and growth of the mesenchymal stem cells market.

Rise in Focus Towards Regenerative Medicine TherapiesMSCs are a good cell source for tissue regeneration because of the following characteristics. MSCs can be sourced from various tissue, including umbilical cord, fetal liver, bone marrow, and synovium. MSCs have the ability to develop into practically any end-stage lineage cell, allowing them to seed specific scaffolds. MSCs are potential immune tolerant agents as they have characteristics such as anti-inflammatory, immunoregulatory & immunosuppressive. Several clinical papers back up MSC-based cell therapy's potential efficacy; while its efficacy is still restricted, the results are encouraging.

MSCs have been investigated and used extensively in regenerative medicine. MSCs have moved closer to therapeutic applications for disease therapy and tissue repair in recent years due to improvements in extraction, culture, and differentiation procedures , therefore future research into better biomaterials and effective inducing factors will help MSCs advance in their regenerative medicine applications.

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Mesenchymal Stem Cells Market Report 2022-2032

Where are the Market Opportunities?

MSC Therapy to Treat Multiple SclerosisThe therapeutic application of MSCs in treating Multiple Sclerosis has proved to provide huge potential by improving clinical symptoms, thereby stabilizing the disease progression. MSCs have properties such as immunomodulator, tissue-protector and repair promotion has proved MSCs to be an attractive therapy option in the treatment of Multiple Sclerosis as well as in other conditions such as inflammation and tissue injury.

MSCs when administered, combat the inflammation in body and regulate the immune system which will further prevent myelin degradation. Clinical trials demonstrating the application of MSCs in Multiple Sclerosis patients have shown increased energy levels, improved flexibility, strength, and mobility. It has also been observed that if MSCs are administered intravenously may have the ability to halt diseases progression for an extended time duration.

MSCs offer intrinsic benefits over hematopoietic stem cells, that MSCs can differentiate into a cell types, release immunoregulatory molecules and promote release of exosome and growth factors

Competitive LandscapeThe major players operating in the mesenchymal stem cells market are Thermo Fischer Scientific Inc., Merck KGaA (Millipore Sigma), STEMCELL Technologoes Inc., Cytori Therapeutics Inc. (Plus Therapeutics Inc.), Cyagen Biosciences, PromoCell GmbH, Celprogen Inc. Stemedica Cell Technologies Inc., Cell Application Inc., Lonza, Celltex Therapeutics Corporation. These major players operating in this market have adopted various strategies comprising M&A, investment in R&D, collaborations, partnerships, regional business expansion, and new product launches.

Recent Developments

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Visiongain is one of the fastest-growing and most innovative independent market intelligence providers around, the company publishes hundreds of market research reports which it adds to its extensive portfolio each year. These reports offer in-depth analysis across 18 industries worldwide. The reports, which cover 10-year forecasts, are hundreds of pages long, with in-depth market analysis and valuable competitive intelligence data. Visiongain works across a range of vertical markets with a lot of synergies. These markets include automotive, aviation, chemicals, cyber, defence, energy, food & drink, materials, packaging, pharmaceutical and utilities sectors. Our customised and syndicatedmarket research reportsoffer a bespoke piece of market intelligence customised to your very own business needs.

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Mesenchymal stem cells market is projected to grow at a CAGR of 13.82% by 2032: Visiongain Research Inc - GlobeNewswire

REDWOOD CITY, Calif., Sept. 26, 2022 (GLOBE NEWSWIRE) -- Jasper Therapeutics, Inc. (NASDAQ: JSPR), a biotechnology company focused on hematopoietic cell transplant therapies, today announced that data from the companys investigator-sponsored study of JSP191 as a conditioning agent in the treatment of Fanconi Anemia were presented at the annual conference of the Inborn Errors Working Party (IEWP), a research group of the European Society of Blood and Marrow Transplantation, held on September 23-25, 2022, in Paris, France.

The study is a Phase 1/2 clinical trial (NCT04784052) utilizing JSP191 to treat Fanconi Anemia patients in bone marrow failure requiring allogeneic transplant with non-sibling donors. The objective of the study is to develop cell therapy for Fanconi Anemia which enables enhanced donor hematopoietic and immune reconstitution with decreased toxicity by transplanting TCR ab+ T-cell/CD19+ B-cell depleted stem cells from a donor, after using JSP191 as a part of conditioning. Primary outcome measures include the number of patients without treatment-emergent adverse events following the administration of JSP191.

In the data series presented, 100% complete donor chimerism was achieved through six months for the first patient and at one month for the second patient. Neutrophil engraftment was reached on day 11 for both patients and platelet engraftment was achieved on days 9 and 14. JSP191 was cleared by day 9 after dosing and no treatment-related adverse events or toxicities were observed.

Patients affected by Fanconi anemia have increased sensitivity to conventional conditioning regimens and radiation due to innate defects in DNA repair, said Ronald Martell, President, and CEO of Jasper Therapeutics. JSP191 offers a targeted conditioning strategy that eliminates the need for radiation or alkylating agents like busulfan. Initial data from this study suggest that a conditioning regimen that includes JSP191 has the potential to achieve successful donor transplant with no JSP191-related adverse events or toxicities reported to date. The positive update presented gives us increased confidence in JSP191, which has now shown promise as a conditioning agent in four indications including acute myeloid leukemia, myelodysplastic syndromes, severe combined immunodeficiency, and Fanconi anemia. We look forward to continuing support for Stanfords investigation of JSP191 and advancing our broader pipeline for JSP191 to the next phase of development.

The details of the oral presentation are as follows:

Title: JSP 191 clinical trial updateSession Name: Conditioning for HSCT in IEIPresenter: Rajni Agarwal-Hashmi, M.D., Professor of Pediatrics and Stem Cell Transplantation, the Stanford University School of MedicineDate/Time: Saturday, September 24, 2022, 2 pm CESTLocation: The Imagine Institute in Paris, France

About Fanconi AnemiaFanconi Anemia (FA) is a rare but serious blood disorder that prevents the bone marrow from making sufficient new red blood cells. The disorder can also cause the bone marrow to make abnormal blood cells. FA typically presents at birth or early in childhood between five and ten years of age. Ultimately it can lead to serious complications, including bone marrow failure and severe aplastic anemia. Cancers such as AML and MDS are other possible complications. Treatment may include blood transfusions or medicine to create more red blood cells, but a hematopoietic stem cell transplant (HSCT) is the only cure.

About JSP191

JSP191 is a humanized monoclonal antibody in clinical development as a conditioning agent that blocks stem cell factor receptor signaling leading to clearance of hematopoietic stem cells from bone marrow, creating an empty space for donor or genetically modified transplanted stem cells to engraft. To date, JSP191 has been evaluated in more than 100 healthy volunteers and patients. Four clinical trials for acute myeloid leukemia (AML)/ myelodysplastic syndromes (MDS), severe combined immunodeficiency (SCID), sickle cell disease (SCD) and Fanconi anemia are currently ongoing. The Company plans a new study of JSP191 as a second-line therapeutic in lower-risk MDS patients in 2022 as well as to a pivotal study in AML/MDS transplant in early 2023. Enrollment in additional studies are planned in patients with chronic granulomatous disease and GATA2 MDS who are undergoing hematopoietic cell transplantation as well as a study of JSP191 as a chronic therapeutic for low to intermediate risk MDS patients.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The company is advancing two potentially groundbreaking programs. JSP191, an anti-CD117 monoclonal antibody, is in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow in patients undergoing hematopoietic cell transplantation. It is designed to enable safer and more effective curative allogeneic hematopoietic cell transplants and gene therapies. In parallel, Jasper Therapeutics is advancing its preclinical mRNA Stem Cell Graft Platform which is designed to overcome key limitations of allogeneic and autologous gene-edited stem cell grafts. Both innovative programs have the potential to transform the field and expand hematopoietic stem cell therapy cures to a greater number of patients with life-threatening cancers, genetic diseases, and autoimmune diseases than is possible today. For more information, please visit us at jaspertherapeutics.com.

Forward-Looking Statements

Certain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements are sometimes accompanied by words such as believe, may, will, estimate, continue, anticipate, intend, expect, should, would, plan, predict, potential, seem, seek, future, outlook and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding the potential long-term benefits of hematopoietic stem cells (HSC) engraftment following targeted single-agent JSP191 conditioning in the treatment of severe combined immunodeficiency (SCID) and Jaspers ability to potentially deliver a targeted non-genotoxic conditioning agent to patients with SCID. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of Jasper and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by an investor as, a guarantee, an assurance, a prediction or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. Many actual events and circumstances are beyond the control of Jasper. These forward-looking statements are subject to a number of risks and uncertainties, including general economic, political and business conditions; the risk that the potential product candidates that Jasper develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; risks relating to uncertainty regarding the regulatory pathway for Jaspers product candidates; the risk that clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release; the risk that Jasper will be unable to successfully market or gain market acceptance of its product candidates; the risk that Jaspers product candidates may not be beneficial to patients or successfully commercialized; patients willingness to try new therapies and the willingness of physicians to prescribe these therapies; the effects of competition on Jaspers business; the risk that third parties on which Jasper depends for laboratory, clinical development, manufacturing and other critical services will fail to perform satisfactorily; the risk that Jaspers business, operations, clinical development plans and timelines, and supply chain could be adversely affected by the effects of health epidemics, including the ongoing COVID-19 pandemic; the risk that Jasper will be unable to obtain and maintain sufficient intellectual property protection for its investigational products or will infringe the intellectual property protection of others; and other risks and uncertainties indicated from time to time in Jaspers filings with the SEC. If any of these risks materialize or Jaspers assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. While Jasper may elect to update these forward-looking statements at some point in the future, Jasper specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Jaspers assessments of any date subsequent to the date of this press release. Accordingly, undue reliance should not be placed upon the forward-looking statements.

Contacts:John Mullaly (investors)LifeSci Advisors617-429-3548jmullaly@lifesciadvisors.com

Jeet Mahal (investors)Jasper Therapeutics650-549-1403jmahal@jaspertherapeutics.com

Excerpt from:
Jasper Therapeutics Announces Positive Clinical Data from Investigator Sponsored Study of JSP191 Conditioning in Fanconi Anemia Patients at IEWP...

Dr. Zachary Prudowsky has never met the woman whose life he helped save by being a bone marrow donor, but he feels a special connection to her.

Prudowsky, a pediatric hematologist/oncologist, was preparing to move to Houston when the National Marrow Donor Program reached out to him in 2018. The nonprofit, which receives funding from Congress to operate its Be The Match registry of volunteer donors in the U.S., told Prudowsky he was a preferred donor for a woman with leukemia.

It wasnt until one year after his donation that he learned the woman lived in Katy and had her bone marrow transplant at M.D. Anderson Cancer Center.

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Absolute serendipity, said Prudowsky, who is now 33. This saved a Texan, which is really, really cool.

She also sent him a note, saying his donation allowed her to meet her newborn grandchild. She referred to herself as granny, which tugged at Prudowskys heartstrings. That's what he calls his own grandmother.

That child gets to grow up with a grandmother because of Be The Match, he said. Thats where its really special for me.

Donate bone marrow: If you are between the ages of 18 and 40 and meet health guidelines, you can sign up to join the Be The Match Registry at bethematch.org. You can sign up online or find a local Be The Match Registry event.

Make a financial donation: You can also sign up to make one-time or monthly donations to the Be The Match Registry, or arrange your own fundraiser, at bethematch.org.

Prudowsky now serves as an advocate for Be The Match and the NMDP, which oversees a registry that includes more than 39 million potential donors. The NMDP helps facilitate more than 7,500 bone marrow transplants each year, Chief Policy Officer Brian Lindberg said.

Prudowsky and Lindberg are now advocating for Congress to pass H.R. 7770, or the Life-Saving Leave Act. The bill, introduced in May by Democratic Rep. Dean Phillips of Minnesota, would amend the Family Medical Leave Act of 1993 to provide up to 40 hours of unpaid, non-consecutive leave for bone marrow or blood stem cell donors.

The bill essentially seeks to guarantee that a donor wont lose his or her job while taking time off to help save a life, Lindberg said.

The thing that we cant do is promise that person that after theyre done with this process that their job will be waiting for them in the end, he said. Thats what this bill is intended to solve.

Prudowsky enrolled as a donor in 2011, during his first year of medical school in South Carolina. He knew he planned to treat cancer and blood disorders for a career, so he felt it made sense for him to sign up.

He didnt hear anything until 2018, near the end of his residency in Ohio. The NMDPreached out to inform him that he was the preferred donor for the Texas woman. Coincidentally, Prudowsky was preparing to move to Texas for a fellowship at Baylor College of Medicine.

He underwent several tests to confirm he was the best match. Less than three months after the call, he made his donation at the Gulf Coast Regional Blood Center in Houston.

Prudowsky donated via a process called peripheral blood stem cell collection (PBSC). Prior to the donation, donors get five days of injections of a drug called filgrastim to increase the number of blood-forming cells in their bloodstream. Those same blood-forming cells are found in bone marrow. The injections are given in outpatient clinics, and there are many instances where donors can return to work immediately afterward, Lindberg said.

On the day of the donation, blood was taken from Prudowskys arm and routed through a machine that collects those blood-forming cells. The rest of his blood was then returned to him through a needle in his other arm. The whole procedure took roughly four hours.

It was pretty uncomplicated, Prudowsky said. I kind of knew what I was getting myself into, but it was not a difficult process by any means.

Approximately 70 to 80 percent of all marrow donations occur via PBSC, Lindberg said.

The rest occur via traditional bone marrow donation, where a donor is put under anesthesia so a physician can collect cells from their hip. After that procedure, donors may experience soreness for the next few days, Lindberg said.

Weve heard it described many times as the kind of soreness that would be involved if you accidentally bumped into the corner of your dining room table.

The 40 hours outlined in the Life Saving Leave Act could be applied to recovery time, Lindberg said.

Prudowskys decision to be a donor while working as a doctor is not unique; both he and Lindberg said they know of others who work in medicine and are also signed up to be potential donors. But actually being matched can be tricky. Genetics has a lot to do with it: roughly 30 percent of patients have a family member who will be a fully-matched donor; the other 70 percent will need an anonymous donor from a registry.

Even then, the odds of finding a match vary greatly by ethnicity. While 79 percent of white patients will find an anonymous match, that drops to just under 50 percent for Asian and Hispanic patients, and to just 29 percent for Black patients, according to the NMDP.

The NMDPdoes help facilitate bone marrow transplants involving international donors and patients to increase the odds of finding a match, Lindberg said.

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However, its critical to keep recruiting a diverse pool of potential donors, Lindberg said. The greater the number, the greater the chance a patient will find a match.

Signing up to be a donor is straightforward, Prudowsky said. Anyone who is interested can sign up online on the Be The Match website. Theyll then submit a swab of the inside of their cheek, he said.

But Lindberg and Prudowsky also feel the Life Saving Leave Act could make the decision to be a donor even more straightforward. The NMDP can help donors by covering lost wages, as well as travel costs and other expenses during the process. But it cant guarantee theyll have a job if they take time off to donate.

There is simply no reason for anyone to be at risk of losing their job when it comes to potentially saving a life, Phillips said in a news release announcing the introduction of the bill.

Thirty-eight states already have laws that offer some level of paid or unpaid leave for bone marrow donors, but they vary widely, Lindberg said. Texas, for example, offers up to five days of leave without a reduction in salary, but the law only applies to state employees. The Life Saving Leave Act would create a uniform, federal standard, Lindberg said.

Lindberg is optimistic that the bill will become law. It has bipartisan support among seven cosponsors. Lindberg also said it has little to no economic impact because the leave is unpaid.

In the meantime, Prudowsky hopes more people will sign up for the Be The Match registry. He's seen his own patients learn they had a match for a bone marrow transplant, so he knows what a difference it can make.

"In my time in medicine, one of the most fulfilling things, if not the most fulfilling thing I've ever done, is this," he said. "And I didn't even have to be a doctor to do it."

evan.macdonald@chron.com

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A Houston doctor who saved a life by donating bone marrow wants to help others do the same. - Houston Chronicle

PARIS Barbra Streisand loved her dog Samantha, aka Sammy. The white and fluffy purebred Coton of Tulear was even present on the steps of the Elyse Palace, the French Presidents official residence, when Streisand received the Legion of Honor in 2007.

As the singer and actress explained inThe New York Times in 2018, she loved Sammy so much that, unable to bring herself to see her pass away, she had the dog cloned by a Texas firm for the modest sum of 50,000 dollars just before she died in 2017, at the age of 14. And that's how Barbra Streisand became the happy owner of Miss Violet and Miss Scarlet, two puppies who are the spitting image of the deceased Samantha.

This may sound like a joke, but there is one deeply disturbing fact that Harvard Medical School genetics professor David A. Sinclair points out in his book Why We Age And Why We Dont Have To. It is that the cloning of an old dog has led to two young puppies.

This proves that DNA ours as well as that of Sammy has everything it takes to restore lost youth. This is a property that could be used to "reverse" aging without having to go through the problematic stage of cloning.

The idea rests on identifying the "reset" button of the organism. And aging specialists all have the same piece of good news to announce: this button has been found.

Its name sounds like a Japanese techno-thriller title: "The Yamanaka factors". But Shinya Yamanaka is not a fictional character. He is a scientist specialized in stem cell research who received the 2012 Nobel Prize in Medicine.

If all this sound a bit too science-fictional, you should know that the U.S. biotech company Altos Labs, which was just founded early this year, received a check of three billion dollars from billionaires Yuri Milner and Jeff Bezos. Not bad for a start-up. But this is a start-up with a very promising technology cellular reprogramming, which is nothing more than the name given by biologists to the famous "reset" button.

In 2006-2007, Yamanaka announced to the scientific community that he had discovered a combination of four genes Oct4, Klf4, Sox2 and c-Myc which, when injected into a cell, induces it to go from being a differentiated cell (nerve, blood, and so on) to being a pluripotent stem cell, i.e., one that can subsequently redevelop into any cell type.

It didn't take long for Yamanaka's colleagues to take advantage of his amazing discovery. In 2011, French researcher Jean-Marc Lematre, who worked at the Institute of Functional Genomics at the University of Montpellier (which never received the same financial support as American biotech company Altos Labs!) was the first to experimentally prove, on human tissues, that cellular aging was a reversible process. He and his team succeeded in transforming aging or senescent human skin cells back into young skin cells.

The process has since been improved, since it is no longer necessary to go through the stage of pluripotent cells which can degenerate into cancerous cells to reverse cellular aging. Interrupting the process before reaching this stage is enough to start the series of gene reactions that counter cellular aging.

But that's not all. Since Lematre's pioneering work, biologists from both sides of the Atlantic have shown that what was possible at the level of the cell is also possible at the level of the organism as a whole. As is often the case, they used mice as guinea pigs. At the end of 2016, in a famous study published by the "Cell" magazine, a professor at the Salk Institute (San Diego, California) Juan Carlos Izpisua Belmonte revealed the more than promising results recorded on genetically modified rodents.

The rodents' genome had been enriched with the Yamanaka factors as well as a small piece of additional genetic code, corresponding to a sort of on-off switch. Controlling the activation of the four genes, this "promoter" was itself activated only if the mouse ingested an antibiotic the doxycycline to be precise.

By prescribing this molecule (and thus activating the Yamanaka factors) two days a week throughout the life of the mice, Belmonte and his team increased their lifespan by 40%. "Aging is no longer a unidirectional process, as we thought. We can slow it down and even reverse it," he announced triumphantly. In a very similar experiment, Jean-Marc Lematre has obtained a more modest lengthening, of 15%, but thanks to a single dose of doxycycline. And above all, insists the French researcher, this "extra" lifespan proved to be free of all age-related diseases: osteoporosis, arthritis, pulmonary or renal fibrosis, etc.

The genetic modification of mice is common practice in labs. But should we do the same with humans to get the same result? There was public outcry in 2018 when Chinese researcher He Jiankui gave birth to twins with tampered genomes the first genetically modified children in history with the objective of giving them resistance to HIV.

How we view "GMO babies" may change over the next few decades. But whether it changes or not, it will not be necessary to go that far to do cell reprogramming in humans. A simple vaccine will probably do the trick.

The Covid-19 pandemic made the public aware that a vaccine whether RNA or DNA could be used as a vector to introduce genetic material into the human body. BioNTech's and Moderna's messenger RNA vaccines do this, but many other "viral vectors" exist, such as adeno-associated viruses (AAVs), small, non-pathogenic DNA viruses commonly used in molecular biology to carry one or more "genes of interest. On paper, there is nothing to prevent these genes of interest from being precisely those highlighted by Yamanaka.

And this is what our near future could look like. Around the age of 30, when we are alas, only temporarily! at the peak of our mental and physical fitness, we would receive one or more injections of this viral vector responsible for carrying Yamanaka's factors into us. Nothing would change in our body yet, as the Yamanaka factors have been programmed to remain silent until activated by the promoter. So we would continue to age normally. The passing of the years would no longer be irreparable!

Indeed, as soon as we would start to feel their first undesirable effects, let's say in our mid-forties, we would be prescribed a month's treatment with doxycycline. And then but only then would the youth therapy kick in. White hair disappearing, wounds healing faster, wrinkles fading, organs regenerating, glasses becoming useless... "Like Benjamin Button," writes David Sinclair, "you would experience the sensations of a 35-year-old. Then 30. Then 25. But unlike Benjamin Button, you would not go beyond that limit, because the statute of limitations would be interrupted... You would be about two decades younger biologically, physically and mentally, without having lost any of your knowledge, wisdom or memories."

Of course, such a possibility, if it becomes a reality and especially if it becomes widespread, will revolutionize large parts of society and will not be without its own tricky problems for a resource-limited planet. But who among us, once we reach a certain age, wouldn't dream of regaining our lost youth, while retaining the "benefits of experience"?

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Benjamin Button For Real? Scientists Are Close To Cracking The Code To Reverse Aging - Worldcrunch

Sep 17, 2022(Nanowerk News) Few human injuries are as catastrophic as those to the spine. An accident, disease or act of violence affecting the spine can result in poor function even paralysis almost anywhere in the body.The spinal column is enormously complex, with limited capacity for regeneration and any health implications are usually long-term and chronic.While there is no known way to repair a spinal cord injury (SCI), scientists may be on the cusp of some important breakthroughs. New approaches are being taken to reverse the nerve damage, with some researchers attempting to reshape the architecture of the spinal cord using materials engineered in the laboratory.Prof Paula Marques, material scientist at the University of Aveiro in Portugal and her colleagues, are seeking to mould a particular biomaterial into a scaffold that can replace damaged spinal tissue. This will create a working bridge over an injured area giving the brain an alternative pathway to communicate with the body.The hope is that, within the next decade, these biomaterials will result in radical new treatments for the 250-500 000 people who suffer a spinal cord injury around the world every year.Even a small improvement in treatment can lead to a big change to quality of life, said Prof Marques.The spinal column is enormously complex. (Image: CHUTTERSNAP via Unsplash)Nerve regenerationIn addition, the scaffold implant would support the regeneration of natural nerve cells, enabling the body eventually to resume its natural function unassisted.Prof Marques is the principal researcher of the NeuroStimSpinal project, an EIC Pathfinder project under Horizon 2020 focusing on graphene-based material combined with a protein-rich material derived from humans known as a 'decellularised extracellular matrix'. In the human body, an extracellular matrix provides the structure and support to living cells.This blend of matrix and graphene-based material creates a 3D structure that skilfully mimics the morphology of the native spinal cord. It will form the backbone as it were of the projects implant.Graphene shows excellent electrical properties, meaning a current can run along it a prerequisite for any material that might be employed to send electrical impulses along the spinal cord.Importantly, the scaffold is porous, meaning cells and spinal fluids can pass through it. Its also biocompatible, preventing rejection by the body, and biodegradable, allowing it to be programmed to degrade over time.Restoring functionProf Marques describes her work as disruptive and says the potential prize of restoring function to people with paralysis is huge.I see real hope, she said. My only frustration is that we cant move forward faster with this research spinal cord injury has such a big impact on human life.There are two main types of cells in nerve tissue: neurons, which transmit electrical impulses, and glial cells, which are non-conductive and provide a support system for the neurons.In lab experiments, the NeuroStimSpinal team which includes experts in material science, electronic engineering, physics and biology have found that when their scaffold is seeded with embryonic neural progenitor cells (cells that renew themselves and have the potential to develop into either neuronal or glial cells) and an electrical stimulus is applied, the blank stem cells successfully differentiate into a mixture of the two cell types.This is very encouraging, said Prof Marques. It shows that the scaffold can provide a good environment for nerve cell regrowth.Her group is one of just a handful around the world that has managed to make neural stem cells develop into new cell lineages in lab conditions.However, to date, no such success has been achieved in live animals. Prof Marques wants her next round of experiments to set SCI research on a new course.In the months ahead, her team will transplant miniature versions of their scaffold into rats. An electric current will be applied to the implant through a control unit inserted under the animals skin to accelerate tissue regrowth. If these experiments show regeneration of the animals spinal cord is possible with the scaffold in place, Prof Marques will apply for fresh funding to take her work to the next level.I hope we can contribute with our scientific knowledge to take a step forward towards SCI repair, she said.Catastrophic strokeA stroke is another catastrophic life event that can result in damage to the nervous system. Strokes, besides being the number two cause of death worldwide, are the third-leading cause of disability-adjusted life years (DALY), a metric used to assess the burden of death and disease.Scientists have yet to find a way to replace the dead brain cells that result from a clot blocking the flow of blood and oxygen to the brain, but they are starting to exploit the latest technology such as advances in virtual reality (VR) to help patients recover from some of the long-term consequences.After a stroke, hands can become stiff due to disrupted connections between the brain and the hand muscles. This spasticity can make it hard, almost impossible, to straighten fingers or grasp an item.These hand impairments can severely impact daily life, said Dr Joseph Galea, a researcher in motor neuroscience at the University of Birmingham in the UK.Though theres been a lot of focus on improving large, reaching-arm movements after a stroke, theres been little work on improving hand functionality.Dr Galea wants to improve hand-movement recovery through the ImpHandRehab project. With funding from the European Research Council, this project asks stroke patients to perform tasks involving increasingly complex hand movements a form of rehabilitation that will ultimately improve dexterity and quality of life. Users perform their tasks wearing a VR headset paired with affordable, off-the-shelf motion-capture gloves.Demonstration of VR training for stroke treatments. (Video: Joseph Galea)What motivates users to stick to their tasks?Immersive VRGaming, explained Dr Galea. Weve developed two really immersive VR games that reward people for doing better and better at something like popping a balloon or controlling a submarine. Weve noticed that the more points or coins are at stake, the harder a person will try and the better theyll perform.Best of all, he and his colleagues have found that after a game has been played for a prolonged period of time, the improved hand performance persists even when the VR headset is removed.We envisage our solution being used by patients at home, said Dr Galea. It would be complementary to traditional rehab techniques.

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Rehabilitating spinal cord injury and stroke with graphene and gaming - Nanowerk

In the present study, we derived two particularly noteworthy results. First, nearly half of the institutions that responded to the study were either currently providing UCB to private banks during the study period or had done so in the past. Second, some institutions were found to provide UCB not only to private banks but also to companies, research institutions, and medical treatment facilities.

During the present study, the APHSCT, along with related ministerial ordinances and guidelines, stipulated how public banks preserve and manage UCB. However, during the study period, these laws and regulations did not require the institutions that handled childbirth to keep records, except when providing UCB to public banks. Consequently, no one knew how many institutions handling childbirth supplied UCB to private banks or the status of UCB distribution. The present study determined that 34.4% of institutions handling childbirth currently provide UCB to private banks, while 16.1% of institutions did so in the past. Our study reported for the first time that these percentages far outstrip those for UCB supply to public banks (6.1% and 8.0%, respectively). These low percentages may be related to the low number of institutions handling childbirth in Japan partnered with public banks (96 institutions as of January 18, 2021) [14,15,16,17,18,19].

However, from the standpoint of appropriate collection, safe preservation, and effective usage of UCB, public and private banks should be regulated according to more uniform standards. More than one-fourth of institutions that provide or have provided UCB to private banks did not provide explanations about UCB collection to UCB donors, while nearly 20% of institutions did not obtain consent. Donors of UCB choose to have their UCB preserved and are also users of UCB who entrust their UCB to private banks, a state of affairs that may lead to the opinion that it is not that important for institutions handling childbirth to provide explanations or obtain consent. However, an MHLW survey reported that private banks do not provide sufficient explanations to users in advance [20]. This state of affairs may be related to the absence of regulations in private banks in Japan.

Even before we demonstrated problems with private banks in Japan in the present study with empirical data, these problems were already known anecdotally, which led many academic associations to issue warnings. In 2002, the Japan Society for Hematopoietic Cell Transplantation issued a statement declaring that private banks were almost completely ineffective, except in cases such as patients with refractory blood diseases within ones own family and that regulations were necessary to ensure proper technical guidelines and safety [21]. In addition, the Japan Association of Obstetricians and Gynecologists declared in 2002 that sufficient understanding was necessary regarding the status and background of private storage of UCB and that careful steps were required to ensure that private banks do not simply use UCB for profit [22].

However, as we analyzed the results of the present study, a relevant concern came to pass. In 2017, physicians who administered UCB to patients without notifying government authorities were found guilty of violating the Act on the Safety of Regenerative Medicine, with the vendor who sold the UCB charged as an accomplice [23, 24]. The UCB sold by the vendor leaked from a private bank that had gone bankrupt in 2009. However, the charge in this case was providing regenerative medicine to patients without reporting it to the MHLW; there was no law targeting the sale of the leaked UCB itself, which was, therefore, beyond the scope of legal penalty [25].

Spurred by the case described above, the MHLW conducted a survey of private UCB banks in Japan [20]. Of the seven vendors whose activities could be confirmed at the time of the survey, six responded; one of these vendors only distributed UCB without preserving it. The UCB held by the remaining five vendors constituted a supply for a total of 45,800 people; roughly 2,100 peoples worth of UCB had not been disposed after the vendors contracts with the donors had ended. One vendor provided UCB to a third party (roughly 160 times). The three vendors involved in the above case later went out of business [26].

Taking the case seriously, the MHLW revised the APHSCT to generally prohibit the collection, preparation, storage, testing, and delivery of UCB for transplantation as a business by entities other than public banks. The revision also stipulated that UCB for transplantation may not be delivered by anyone for commercial purposes. However, these prohibitions do not apply when a public bank delivers UCB, when UCB is used in the treatment of a blood relative to the donor, or when approval is granted by the MHLW. Violations of these prohibitions are subject to criminal penalties. Consequently, the two private banks that obtained approval from the MHLW were permitted to continue their activities.

However, regardless of legal permission, there is still the question of whether private UCB banks, which handle UCB for profit, are ethically permissible. For example, the 2004 European Commissions Group on Ethics in Science and New Technologies stated that while they did not completely disavow for-profit biobank activities, these activities engender ethical criticism. The group also stated that the human body in principle is not an object of commercial value and recommended that private biobank activities operate under strict conditions such as appropriate management by regulatory authorities [27]. Meanwhile, a non-Japanese study has reported that the possibility of UCB being used 20years later by the person who requested its preservation or by their family is an incredibly low 0.040.0005% [28]. The extent to which this information is explained to potential private bank users is unknown. In fact, the previously cited survey by the MHLW indicated that the role of public UCB banks and the actual utility of the UCB stored in the private banks were not sufficiently explained to users [20]. Future research must thoroughly examine the status of UCB private banks following revision of the law and compare the results of this examination to the findings of the present study.

A small number of institutions handling childbirth surveyed in the present study responded that they currently provide or used to provide UCB to medical treatment facilities (2.6%), research institutions (5.9%), companies (2.2%), or foreign medical treatment facilities, research institutions, or companies (0.3%). Some institutions handling childbirth also either currently store or used to store UCB themselves for treatment or research (2.3% and 3.2%, respectively). This aspect of the status of UCB distribution has never been demonstrated in a previous study.

Since the revision of the APHSCT, the delivery of UCB for transplantation has been strictly prohibited except in the cases of provision to a public bank, provision to a private bank approved by the MHLW, and use for treatment by a blood relative. Thus, it is currently considered illegal for institutions handling childbirth to deliver UCB to other facilities domestically or internationally or to store UCB themselves for treatment purposes. However, the revised law still does not apply to the handling of UCB for research purposes, that is, basic studies and the development of treatments. In addition, while there are laws and local ordinances that call for the incineration or burial of UCB according to specific methods, these regulations generallydo not cover the delivery of UCB for research purposes.

At a glance, there would seem to be no problem with an institution that handles childbirth providing UCB to a third party or storing UCB itself for research purposes. However, the results of the present study, which found that a certain number of institutions handling childbirth do not provide explanations or obtain consent when UCB is harvested from private bank users, and the results of the above-cited MHLW survey, which found that private banks also fail to provide users with sufficient explanations, cast doubt amidst the absence of relevant laws and regulations as to how much has been suitably explained to UCB donors when they consent to be third-party UCB donors.

We did not determine what sort of explanations institutions handing childbirth give when they deliver UCB to other institutions or store it themselves for research purposes, nor did we determine methods for obtaining consent, as we felt these fell outside the aim of the present study. Future studies must answer these questions and evaluate if there truly is no problem with the current state of affairs in Japan in the absence of rules regarding the harvest or delivery of UCB for research purposes by institutions handling childbirth.

The present study had several limitations. First, the response rate was only 36.7%, which is not at all high. However, the percentages of institutions handling childbirth by type that responded to our survey are roughly consistent with those of Japanese medical treatment facilities overall [29], implying that our results are representative to some extent. Of course, we cannot rule out the effect of non-responder bias. However, the present study can be considered sufficiently significant because this is the first study to determine the status of UCB delivery by Japanese institutions handling childbirth to private banks, other companies, research institutions, and medical treatment facilities. The 3,277 facilities included in this study represent 99.9% of childbirth facilities in Japan. The total number of facilities in Japan is approximately 3,280. Of which 1,084 facilities responded that they handled childbirth. A simple calculation from the actual number of births in 2016 (976,978 births), a year before this study was conducted [30], allowed us to estimate that the facilities included in our study handled a total of 322,879 births. The number of UCBs managed by these facilities can be considered significant. In addition, by determining the status of UCB delivery prior to revision of the APHSCT, we have made it possible to determine the effects of APHSCT via comparisons with post-revision survey results.

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Current status of umbilical cord blood storage and provision to private biobanks by institutions handling childbirth in Japan - BMC Medical Ethics -...

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Predicting the risk of acute kidney injury after hematopoietic stem cell transplantation: development of a new predictive nomogram | Scientific...

ThisBone Marrow MarketReport provides details on Recent New Developments, Trade Regulations, Import-Export Analysis, Production Analysis, Value Chain Optimization, Market Share, Impact of Domestic and Localized Market Players, Analyzes opportunities in terms of emerging revenue pockets, changing market regulations, strategic market growth analysis, market size, market category growth, niche and application dominance, product endorsements, product launches, geographic expansions , technological innovations in the market.For more information on the bone marrow market, please contact Data Bridge Market Research for a summary of theanalyst, our team will help you make an informed market decision to achieve market growth.

Bone Marrow Market is expected to experience market growth during the forecast period of 2021 to 2028. Data Bridge Market Research analyzes that the market is growing with a CAGR of 5.22% during the forecast period of 2021 to 2028 and it is projected to reach USD 13,899.60 Million by 2028. The increasing number of bone marrow diseases will help accelerate the growth of the bone marrow market.Bone marrow transplant also called hematopoietic stem cell.It is a soft vascular tissue present inside the long bones.It includes two types of stem cells, namely hematopoietic and mesenchymal stem cells.The bone marrow is primarily responsible for hematopoiesis (blood cell formation), lymphocyte production, and fat storage.

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The main factors driving the growth of the bone marrow market during the forecast period are the growth in the incidence of non-Hodgkins and Hodgkins lymphoma, thalassemia, and leukemia, as well as common bone marrow diseases worldwide, developments in technology and improvements.in health infrastructure.In addition, advanced signs of bone marrow transplantation for cardiac and neural disorders, increased funding for logistics services, and rising health care spending per capita are some of the other factors expected to further drive growth. growth of the bone marrow market in the coming years.years.However, the high costs of treatment,

Key Players Covered in the Bone Marrow Market Report are AGendia, Agilent Technologies, Inc., Ambrilia Biopharma Inc., Astellas Pharma Inc., diaDexus, Illumina, Inc., QIAGEN, F Hoffmann-La Roche Ltd, Sanofi, Stryker Corporation, PromoCell GmbH, STEMCELL Technologies Inc., Lonza, ReachBio LLC, AllCells, ATCC, Lifeline Cell Technology, Conversant bio, HemaCare, Mesoblast Ltd., Merck KGaA, Discovery Life Sciences, ReeLabs Pvt. Ltd., Gamida Cell, among others national and global players.Market share data is available separately for Global, North America, Europe, Asia-Pacific (APAC), Middle East and Africa (MEA), and South America.DBMR analysts understand competitive strengths and provide competitive analysis for each competitor separately.

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Bone MarrowMarket Scope and Market Size

The bone marrow market is segmented based on transplant type, disease indication, and end user.Growth between these segments will help you analyze weak growth segments in industries and provide users with valuable market overview and market insights to help them make strategic decisions to identify leading market applications.

Country-level analysis of thebone marrow market

The bone marrow market is analyzed and information is provided on market size and trends by country, transplant type, disease indication, and end user, as mentioned above.Countries Covered in Bone Marrow Market Report are USA, Canada, and Mexico, North America, Germany, France, UK, Netherlands, Switzerland, Belgium, Russia, Italy, Spain, Turkey, Rest of Europe in Europe, China, Japan, India, South Korea, Singapore, Malaysia, Australia, Thailand, Indonesia, the Philippines, Rest of Asia-Pacific (APAC) in the Asia-Pacific region (APAC), Saudi Arabia, United Arab Emirates , South Africa, Egypt, Israel, Rest of the Middle East and Africa (MEA) under Middle East and Africa (MEA), Brazil,

Europe dominates the bone marrow market due to the proliferation of innovative health centers.Furthermore, the health systems have introduced bone marrow transplantation in their contributions and state-of-the-art public facilities that will further drive the growth of the bone marrow market in the region during the forecast period.North America is expected to witness significant growth in the bone marrow market due to increasing cases of chronic diseases such as blood cancer.In addition, the increase in the geriatric population is one of the factors that is expected to drive the growth of the bone marrow market in the region in the coming years.

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The country section of the Bone Marrow market report also provides individual market impact factors and regulatory changes in the country market that affect current and future market trends.Data points such as consumption volumes, production sites and volumes, import and export analysis, price trend analysis, raw material cost, Downstream and Upstream value chain analysis are some of the main indicators used to forecast the scenario. of the market for each country.Additionally, the presence and availability of global brands and the challenges they face due to significant or rare competition from local and national brands,

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Bone Marrow market estimated to reach US$13899.60 Million during the forecast period - Digital Journal

Five people with the autoimmune condition lupus are now in remission after receiving a version of CAR-T therapy, which was originally developed for cancer

By Clare Wilson

Illustration of a CAR-T cell

CHRISTOPH BURGSTEDT/SCIENCE PHOTO LIBRARY

A high-tech cell therapy used to treat cancer has been repurposed as a treatment for lupus, an autoimmune condition that can cause joint, kidney and heart damage.

CAR T-cell therapy has put all five people with lupus treated so far into remission. The participants have been followed up for an average of 8 months, with the first person treated 17 months ago. Thats kind of unheard of, says Chris Wincup at Kings College London, who wasnt involved in the study. This is incredibly exciting.

But it is too soon to know how long the remissions will last, says Georg Schett at the University of Erlangen-Nuremberg in Germany, who was part of the study team.

CAR T-cells were developed to treat blood cancers that arise when B cells, a type of immune cell that normally makes antibodies, start multiplying out of control.

The approach requires taking a sample of immune cells from a persons blood, genetically altering them in the lab so they attack B cells and then infusing them back into the individuals blood. It seems to put 4 out of 10 people with these kinds of cancers into remission.

Lupus, also called systemic lupus erythematosus, is caused by the immune system mistakenly reacting against peoples own DNA. This is driven by B cells making antibodies against DNA released from dying cells.

It is currently treated with medicines that suppress the immune system or, in more severe cases, with drugs that kill B cells. But the treatments cant kill all the B cells, and if the disease flares up badly, some people develop kidney failure and inflammation of their heart and brain.

Schett and his team wondered whether using CAR T-cells to hunt down all the B cells would be more effective. Within three months of receiving the treatment, all five participants were in remission, without needing to take any other medicines to control their symptoms.

The CAR T-cells were barely detectable after one month, and after three and a half months, the volunteers B cells started to return, having been produced by stem cells in bone marrow. These new B cells didnt react against the DNA.

We dont know what normally causes B cells to start reacting against DNA in people with lupus, so it is possible that some kind of trigger may start the process happening again, says Wincup.

The achievement means CAR T-cells may also be useful against other autoimmune diseases that are driven by antibodies, such as multiple sclerosis (MS), in which the immune system attacks nerves, says Schett.

Another radical treatment for MS involves rebooting the immune system by destroying it with chemotherapy. By comparison, CAR T-cells would be less invasive and more tolerable, he says.

But it is too soon to know how effective CAR T-cells will be for autoimmune conditions, says Wincup. This is a small number of patients, so we dont know if this is going to be the result for everyone.

When used in cancer, CAR T-cells are expensive to create for each person, so they may only be used for autoimmune conditions in people with severe disease when no other treatments are available, he says.

Journal reference: Nature Medicine , DOI: 10.1038/s41591-022-02017-5

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Radical lupus treatment uses CAR T-cell therapy developed for cancer - New Scientist

Introduction:Aplastic anemia (AA)is characterized by pancytopenia and hypocellular marrow in the absence of an abnormal infiltrate or increase in reticulin fibrosis. The diagnosis of AA is challenging at times due to decreased cellularity and overlapping morphological features with other bone marrow failure syndromes. Hepatitis-associated aplastic anemia (HAAA) is a rare variant in which patients typically present with jaundice and hepatitis followed by pancytopenia almost within 6 months. Post-hepatitis AA accounts for approximately 1-5%of cases, and invariably such cases are negative for the known hepatitis virus as well. There is limited literature available to understand the correlation of AA with hepatitis with none reported at the national level in our region. As AA is relatively more prevalent in Southeast Asia as compared to the western world and hepatitis is a prevalent disease in our population, the main purpose of this study was to assess the hepatic profile and determine the association of hepatitis in AA at the time of diagnosis.

Materials and methods:A cross-sectional study was carried out at the National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, from November 2019 to December 2020 after the informed consent from patients. The study included all treatment-nave patients of acquired AA with no prior history of taking steroids, immunosuppressive treatment, or chemoradiation therapy. Liver function tests, complete blood count, prothrombin time (PT), and activated partial thromboplastin time were performed, along with viral profiles (HAV, Hep B, Hep C, and HIV). SPSS version 23 (IBM Corp., Armonk, NY) was used for statistical analysis. Mean and standard deviations were computed for quantitative variables while percentages and frequencies were reported for qualitative variables. T-test was used to observe the main difference between groups and a p-value <0.05 was considered to be significant.

Results:Out of a total of 351 patients, 29 (8.2%) patients with AA tested positive for viral hepatitis. Hepatitis A was the most prevalent hepatitis (4.0%), followed by hepatitis C (3.7%). The comparison of platelet counts in patients with and without hepatitis was reported to be of statistical significance (p-value < 0.05). A significant statistical difference (p-value< 0.0001) was found in platelet count and PTin patients of AA with and without hepatitis.

Conclusion:Overall, this study revealed that <10% of patients of AA had a positive screening for hepatitis A, B, and C and low platelet count, and PT was statistically significant when compared between the patients with and without hepatitis. Hepatitis being prevalent in our part of the world might have an important causal association with AA. Patients with AA should be screened for liver functions and viral hepatitis at the time of diagnosis. In addition to hepatitis A, B, and C and HIV, other causes of hepatitis should also be screened such as parvovirus B19, human herpes virus 16, and adenovirus which are not included in routine diagnostic viral testing panel.

The distinctive manifestation(s) of aplastic anemia (AA) are pancytopenia and hypocellular bone marrow without evidence of infiltration, dysplasia, and fibrosis. It is caused by several risk factors including infections, toxins, chemotherapeutic drugs, and radiation but the precise cause remains unclear [1]. An uncommon form of AA known as hepatitis-associated aplastic anemia (HAAA) occurs when pancytopenia develops simultaneously with or within six months after an elevated serum alanine aminotransferase (ALT) level. Significantly, these ALT levels are five times higher than the upper limit of normal. Post-hepatitic AA accounts for approximately 1-5% of cases invariably, and such cases are negative for the known hepatitis virus as well [2].When compared to patients with non-hepatitis-associated AA in the pediatric population, those with HAAA have considerably lower survival and prognosis [3]. Hepatitis symptoms linked to HAAA can be self-limiting, but sometimes showmoderate to severe or acute to the chronic clinical course[4]. Necrosis of the portal region and fibrosis that extends up to the centrilobular area can be found in the transjugular liver biopsy of HAAA patients and chronic severe hepatic inflammation quickly progresses to liver fibrosis [5]. First-line therapies include stem cell transplantation from a sibling donor who matches the patient's human leukocyte antigen (HLA) profile or immunosuppressive therapies like cyclosporine and/or antithymocyte or antilymphocyte globulin [6,7].

The exact etiology of hepatitis causing AA is nearly unknown and the pathogenesis of HAAA has been associated with activated T1 cells [8]. Hepatitis B and C virus, parvovirus B19, human herpes virus 16, and transfusion-transmitted virus (hepatitis B, C, HIV) can all be causal associations. The traits include CD8+-predominant lobular necroinflammatory and endothelial damage associated with sinusoidal obstruction syndrome, conjugated hyperbilirubinemia, elevated antinuclear antibody titers, and elevated transaminases [9]. Dietary or nutrition supplements at times may also result in toxin-induced hepatitis [10].It is typical for intrabiliary cholestasis and liver toxicity to result in the apoptotic killing of hematopoietic cells by CD8 lymphocytes and T cell-induced gamma interferon, which leads to hepatitis. Clinical symptoms include pallor, exhaustion, petechial rash, and infections due to pancytopenia [11]. When severe thrombocytopenia and anemia appear at the same time as HAAA, it is important to distinguish this condition from infantile giant cell hepatitis with autoimmune hemolytic anemia [12].

Allogeneic bone marrow transplantation (allo BMT) is the conventional curative treatment for HAAA from an HLA-matched donor. Since HAAA has a poor prognosis, allo BMT has been the curative form of treatment [13-15]. On the other hand, immunosuppressive medication results in a response rate of 70% and a survival rate of 85% for patients not receiving hematopoietic cell transplantation, respectively [16]. Children respond to BMT better than adults do, and the survival rates of patients receiving bone marrow from HLA-matched donors are found to be comparable to that of the patients with AA not caused by hepatitis [17]. There is no recognized antiviral medication for hepatitis B-related HAAA. Lamivudine, a nucleoside analog, has been studied for use in treating hepatitis B-related HAAA, and it has been shown to be effective in causing remission in cases of severe AA and hepatitis B virus infection. Because of its myelosuppressive effects, interferon, an acclaimed antiviral agent in the treatment arsenal of HBV- and HCV-mediated infections, cannot be used as a treatment option for the HAAA [18]. Patients with HAAA exhibit severe pancytopenia following an episode of acute hepatitis, and if left untreated, the marrow suppression is frequently swift and severe.

In Pakistan, cases of hepatitis have been increasing over time, and given the current policies and practices, eradicating hepatitis from Pakistan by 2030 seems unreasonable[19]. We have also noted a rising trend in the incidence of AA than reported internationally. The association of hepatitis with AA is underreported and limited literature is available regarding the determinants of AA. Hepatitis might be one of the causes of AA and it must be considered an alarming situation.The only curative option for AA is BMT, which is an unaffordable treatment option for many patients in Pakistan. Therefore, the aim to conduct this study was to evaluate the hepatic status in relation to hepatitis in treatment-nave AA patients.

This was a cross-sectional study carried out at the National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD & BMT). Patients were recruited between November 2019 and December 2021. Prior to the initiation of the study, approval was taken from the NIBD ethics committee bearing NIBD/RD-188/11-2019 and informed consent was taken from the participants prior to enrollment in the study. The study included all treatment-nave patients of acquired AA with no prior history of taking steroids, immunosuppressive treatment, or chemoradiation therapy. Patients with positive chromosomal breaks (Fanconis anemia) or inherited bone marrow failure were excluded. WHO sample size calculator was used to calculate the sample size, and by taking the percentage reported in the literature (5%) [14] it was found to be at least 73, and hence we recruited 351 patients who visited during the study duration.Non-probability purposive sampling method was used for patient selection. Demographicand laboratory parameters were recorded through a structured questionnaire and the diagnosis of AA was confirmed on bone marrow biopsy. Liver function tests (LFTs), complete blood count (CBC), prothrombin time (PT), and activated partial thromboplastin time (APTT) were performed. PT and APTT were run on STAGO and Sysmex CA-1500, and CBC was performed using a Sysmex XN-1000 analyzer from the Sysmex Corporation in Kobe, Japan. LFTs were performed on a Cobas C 111 analyzer machine that runs on a spectrophotometer principle.Within 2 hours of the blood sample collection, an aseptic setting was used to take a 4 ml blood sample from each patient, which was then tested for the presence of hepatitis A, HBV, HCV, and HIV. Detection of hepatitis B surface antigen and anti-hepatitis C antibodies was done using the chemiluminescence technique. To confirm chronic HCV and HBV infection in individuals with positive antibody tests, a qualitative nucleic acid test was employed as the initial diagnosis of a suspected acute infection. Ultrasound was done to complement the diagnosis of hepatitis. The data were entered in MS Excel and analysis was done by using Statistical Package for Social Sciences (SPSS) version 23.0 (IBM Corp., Armonk, NY). Shapiro-Wilk test was performed for normality and data were found normally distributed. Mean and standard deviations were computed for quantitative variables and percentages and frequencies were reported for qualitative variables. T-test was used to observe the mean difference between the two groups and a p-value <0.05 was found to be significant statistically.

A total of 351 patients were enrolled, out of which 222 (63%) were males, 265 (76%) were unmarried, 11 (3.1%)had hypertension, and 9 (2.5%) had diabetes. The mean age of participants was 30.9 27.5. Twenty-nine (8.2%) patients with AA had hepatitis. The most common hepatitis was hepatitis A, 14 (4.0%), followed by hepatitis C, 13 (3.7%). The most common form of hepatitis C was acute 9 (69.2%). Two patients had compensated cirrhosis and two patients had decompensated cirrhosis (Table 1).

The association of CBC parameters such as hemoglobin, red blood cell count, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, total leukocyte count, neutrophils, lymphocytes, monocytes, and platelets with the patients with and without hepatitis was assessed and it was found out that platelet counts were statistically significant (p-value: 0.0020) as shown in Table 2.

Table 3 depicts the association of liver profile such as serum glutamate pyruvate transaminase, gamma glutamyl transferase (GGT), serum glutamic oxaloacetic acid transaminase, PT, APTT, and international normalized ratio with the patients with and without hepatitis, and it was found out that PT (p-value< 0.0001) was statistically significant.

In our study, 8.2% of AA patients had hepatitis. This is comparatively high as compared to theprevalence of hepatitis in the general population in Pakistan, which is reported to be around 4% [20]. A retrospective study carried out in Europe from 1997 to 2007 demonstrated that HAAA patients had a slight male predominance with a value of 68% [21], which is close to the prevalence of male participants in our study, i.e. 63.2%. This European study also demonstrated that there was no causative virus for hepatitis in 94% of HAAA patients. However, 15 patients (6%) had hepatitis with nine having hepatitis B virus and six having hepatitis A virus [21]. Similar results have been observed in our study with 91.4% HAAA serologically negative and not having any signs or symptoms of hepatitis. Twenty-nine patients (8.3%) had evidence of hepatitis: hepatitis A virus in 14 patients, hepatitis B virus in 2, and hepatitis C virus in 13 patients. Assessing the association of hepatitis C virus with HAAA, a study conducted in France showed that 15.8% of HAAA patients had hepatitis C virus [22], which was approximately three-fold higher compared to our study suggesting a prevalence of 3.7% of HAAA patients with hepatitis C virus. On the contrary, slightly similar figures were recreated in another comparative study done in Thailand which showed that 5.7% of the patients who were never transfusedwere found to have hepatitis C virus [23].

During the initial course of hepatitis, cytotoxic T lymphocytes (CTLs) occupy the same receptor antigen between liver and bone marrow cells. These CTLs replicate and extend to destroy bone marrow hematopoietic stem cells and result in AA [24,25].However, another interesting finding of our study was that AA patients with hepatitis had considerably high platelet counts compared to those without hepatitis (29 28 vs 4 3). This finding is also in concordance with a study conducted by Wang WH et al. [3] in which the HAAA group had a considerably higher platelet count compared to the non-hepatitis-associated AA (50 109/L vs 12 109/L).

Literature reveals that amongthe most frequently assessed values in HAAA, there is a significant rise in ALT, GGT, and serum alkaline phosphatase [26]. The elevated levels are also shown in our results (Table 3). Considerable discrepancies were observed in PT in AA patients with and without hepatitis. This could be on account of viral hepatitis causing deranged LFTs [27].However, studies comparing the levels of liver enzymes between hepatitis-associated and non-hepatitis-associated AA are not extensively reported in the literature.

To the best of our knowledge, this is the first study at the national level to determine the association of hepatitis in patients with AA. However, the limitations of our study were that it was of cross-sectional nature and included non-probability sampling. Prospective cohort studies with stringent inclusion and exclusion criteria, a large sample size, and a controlled environment are needed to validate the findings.

AA is a heterogeneous disease with a limited approach to curative treatment options like allogeneic stem cell transplant in our region. Hepatitis being prevalent in our part of the world might have an important causal association with AA. Patients should be screened for viral hepatitis at the time of diagnosis. Moreover, other causes of hepatitis should also be screened at the time of diagnosis such as parvovirus B19, human herpes virus 16, and adenovirus. Based on the rapidly advancing research methodologies, it is necessary to comprehensively analyze the underlying mechanisms of HAAA.

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Assessment of Hepatic Profile in Acquired Aplastic Anemia: An Experience From Pakistan - Cureus

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Todos Medical Announces NFL Hall of Famer Michael Irvin as Tollovid™ Sports Ambassador for #TolloUp Campaign

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Intellia and Regeneron Announce Initial Data from the Cardiomyopathy Arm of Ongoing Phase 1 Study of NTLA-2001, an Investigational CRISPR Therapy for...

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