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UCLA doctors test stem-cell therapy to improve blood flow in …

By daniellenierenberg

Marty Greenfield with UCLA doctors

Marty Greenfield lives with crushing pain every day due to angina, a condition that is caused by an inadequate supply of blood to the heart. He has suffered a heart attack, and a coronary bypass procedure and angioplasty have provided little relief. His doctor referred him to UCLA to be considered for a heart transplant.

Dr. Jonathan Tobis, a UCLA clinical professor of cardiology, performed an angiogram and angioplasty on Greenfield, 64, but found that the patient was not a candidate for a heart transplant because his heart muscle function was still good.

Instead, Tobis suggested that Greenfield consider participating in a Phase 3 clinical trial that uses a patient's own blood-derived stem cells to try to restore circulation to the heart. The procedure uses the latest technology to map the heart in 3-D and guides the doctor to deliver the stem-cell injections to targeted sites in the heart muscle.

On Oct. 17, Greenfield became the first patient at UCLA to participate in the multicenter clinical trial. He said he jumped at the chance to help, even though the study is double blind, which means that neither the patients nor the researchers know who is receiving stem-cell injections and who is receiving placebos.

"This just isn't about me," said Greenfield, a married father of two sons who lives near Las Vegas. "If I can help move this research forward so that it helps just one person, it will be worth it."

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Administration of cardiac stem cells in patients with ischemic …

By raymumme

BACKGROUND:

SCIPIO is a first-in-human, phase 1, randomized, open-label trial of autologous c-kit(+) cardiac stem cells (CSCs) in patients with heart failure of ischemic etiology undergoing coronary artery bypass grafting (CABG). In the present study, we report the surgical aspects and interim cardiac magnetic resonance (CMR) results.

A total of 33 patients (20 CSC-treated and 13 control subjects) met final eligibility criteria and were enrolled in SCIPIO. CSCs were isolated from the right atrial appendage harvested and processed during surgery. Harvesting did not affect cardiopulmonary bypass, cross-clamp, or surgical times. In CSC-treated patients, CMR showed a marked increase in both LVEF (from 27.5 1.6% to 35.1 2.4% [P=0.004, n=8] and 41.2 4.5% [P=0.013, n=5] at 4 and 12 months after CSC infusion, respectively) and regional EF in the CSC-infused territory. Infarct size (late gadolinium enhancement) decreased after CSC infusion (by manual delineation: -6.9 1.5 g [-22.7%] at 4 months [P=0.002, n=9] and -9.8 3.5 g [-30.2%] at 12 months [P=0.039, n=6]). LV nonviable mass decreased even more (-11.9 2.5 g [-49.7%] at 4 months [P=0.001] and -14.7 3.9 g [-58.6%] at 12 months [P=0.013]), whereas LV viable mass increased (+11.6 5.1 g at 4 months after CSC infusion [P=0.055] and +31.5 11.0 g at 12 months [P=0.035]).

Isolation of CSCs from cardiac tissue obtained in the operating room is feasible and does not alter practices during CABG surgery. CMR shows that CSC infusion produces a striking improvement in both global and regional LV function, a reduction in infarct size, and an increase in viable tissue that persist at least 1 year and are consistent with cardiac regeneration.

This study is registered with clinicaltrials.gov, trial number NCT00474461.

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stem cell therapy treatment for Quadriplegic Cerebral Palsy by dr alok sharma, mumbai, india – Video

By raymumme


stem cell therapy treatment for Quadriplegic Cerebral Palsy by dr alok sharma, mumbai, india
improvement seen in just 3 months after stem cell therapy treatment for quadriplegic cerebral palsy by dr alok sharma, mumbai, india. Stem Cell Therapy done ...

By: Neurogen Brain and Spine Institute

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stem cell therapy treatment for dystonic cerebral palsy by dr alok sharma, mumbai, india – Video

By daniellenierenberg


stem cell therapy treatment for dystonic cerebral palsy by dr alok sharma, mumbai, india
improvement seen in just 3 months after stem cell therapy treatment for dystonic cerebral palsy by dr alok sharma, mumbai, india. Stem Cell Therapy done date...

By: Neurogen Brain and Spine Institute

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Bone Marrow/Stem Cell Transplant | UCLA Transplantation Services …

By raymumme

The UCLA Program is a combined program caring for patients with Hematologic Malignancies receiving chemotherapy and those patients for whom Stem Cell Transplantation is the therapy of choice. The treatmentof blood and marrow cancers includecurrently available therapies, investigational drugs and treatments, as well as stem cell transplantation. Our physicians meet weekly to discussindividual treatment approachesas part of developing a coordinated treatment recommendation.

Bone Marrow Transplantation was first performed at UCLA in 1968 using a related allogeneic transplant to treat an 18 month old child with severe combined immunodeficiency syndrome. The UCLA Marrow Transplantation Program was formally initiated in 1973. Unrelated donor marrow transplants have been carried out at UCLA since 1987, and Cord Blood Transplants have been performed at UCLA since 1996. Autologous transplants have been performed at our program since 1977. Since 1992 most of the Autologous Transplants have utilized Peripheral Blood Stem Cells. Since 1998 an increasing number of the Allogenic Transplants have utilized Peripheral Blood Stem Cells. From inception to the completion of 2007 we have performed 3726 transplants (3080 transplants in the adult population and 646 in the pediatric population).

For decades, this comprehensive program has provided a full range of services as a local, regional, national, and international referral center for transplantations for selected malignancies:

Our goals include finding new and innovative treatments for malignancies and expanding the effectiveness and applicability of bone marrow transplantation through such means as biologic response modifiers, growth factors, and chemotherapeutic agents.

Protocols involving chemotherapy with or without radiation therapy for patients in remission or relapse are available using bone marrow or peripheral blood stem cells from allogeneic, autologous and unrelated donors.

A bone marrow transplant is a procedure that transplant healthy bone marrow into a patient whose bone marrow is not working properly. A bone marrow transplant may be done for several conditions including hereditary blood diseases, hereditary metabolic diseases, hereditary immune deficiencies, and various forms of cancer.

Visit our Health Library to learn more:

Bone MarrowTransplant

How to Schedule Your Evaluation Appointment at UCLA

The United Network for Organ Sharing (UNOS) provides a toll-free patient services lines to help transplant candidates, recipients, and family members understand organ allocation practices and transplantation data. You may also call this number to discuss problems you may be experiencing with your transplant center or the transplantation system in general. The toll-free patient services line number is 1-888-894-6361

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Bone marrow transplant: MedlinePlus Medical Encyclopedia

By NEVAGiles23

A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells.

Bone marrow is the soft, fatty tissue inside your bones. Stem cells are immature cells in the bone marrow that give rise to all of your blood cells.

There are three kinds of bone marrow transplants:

Before the transplant, chemotherapy, radiation, or both may be given. This may be done in two ways:

A stem cell transplant is done after chemotherapy and radiation is complete. The stem cells are delivered into your bloodstream usually through a tube called a central venous catheter. The process is similar to getting a blood transfusion. The stem cells travel through the blood into the bone marrow. Most times, no surgery is needed.

Donor stem cells can be collected in two ways:

A bone marrow transplant replaces bone marrow that either is not working properly or has been destroyed (ablated) by chemotherapy or radiation.

Your doctor may recommend a bone marrow transplant if you have:

A bone marrow transplant may cause the following symptoms:

Possible complications of a bone marrow transplant depend on many things, including:

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Bone marrow transplant: MedlinePlus Medical Encyclopedia

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stem cell therapy treatment for Cerebral Palsy with Hemiplegia by dr alok sharma, mumbai, india – Video

By raymumme


stem cell therapy treatment for Cerebral Palsy with Hemiplegia by dr alok sharma, mumbai, india
improvement seen in just 5 days after stem cell therapy treatment for cerebral palsy with hemiplegia by dr alok sharma, mumbai, india. Stem Cell Therapy done...

By: Neurogen Brain and Spine Institute

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Bone-Derived Stem Cells for Heart Repair | Worldhealth.net Anti …

By NEVAGiles23

Stem cell therapy for heart disease has demonstrated safety and efficacy in clinical trials, but a key for better clinical outcomes is to determine the optimal stem cell type best suited for cardiac regeneration, Steven B. Houser, from Temple University (Pennsylvania, USA), and colleagues report that cortical bone-derived stem cells (CBSCs) may be superior to cardiac stem cells, for the regeneration of heart tissue. The researchers collected CBSCs from mouse tibias. The particular mice used had been engineered with green fluorescent protein (GFP), which meant that the CBSCs carried a green marker to allow for their later identification. The cells were then expanded in petri dishes in the laboratory before being injected directly into the hearts of non-GFP mice that had suffered heart attacks. Some mice received cardiac stem cells instead of CBSCs. In the following weeks, as the team monitored the progress of the mice, they found that the youthfulness of the CBSCs had prevailed. The cells had triggered the growth of new blood vessels in the injured tissue, and six weeks after injection, they had differentiated, or matured, into heart muscle cells. While generally smaller than native heart cells, the new cells had the same functional capabilities, and overall they had improved survival and heart function. The study authors submit that: CBSCs improve survival, cardiac function, and attenuate remodeling through the following 2 mechanisms: (1) secretion of proangiogenic factors that stimulate endogenous neovascularization, and (2) differentiation into functional adult myocytes and vascular cells.

Duran JM, Makarewich CA, Sharp TE, Starosta T, Zhu F, Hoffman NE, Houser SR, et al. Bone-derived stem cells repair the heart after myocardial infarction through transdifferentiation and paracrine signaling mechanisms. Circ Res. 2013 Aug 16;113(5):539-52.

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Study to infuse stem cells into coronary artery to regenerate …

By Sykes24Tracey

Medical investigators are embarking on a study that involves infusing 10 million stem cells directly into a coronary artery of heart attack patients in an effort to regenerate tissue that otherwise would be forever damaged.

Regeneration has been an ongoing theme in science fiction and a goal of real-life scientists.

Dr. Luis Gruberg, of the Stony Brook Heart Institute, and Dr. Allen Jeremias, director of the intensive care unit, led a team late last month in a novel case, which they describe as a clinical trial designed to harvest, and then inject, a patient's own stem cells into the blocked artery responsible for the attack.

"This is a post-heart attack procedure and it is for patients who have had a large heart attack," said Gruberg, director of interventional cardiology research.

In patients whose attacks are severe, vast portions of the heart are irreparably damaged, resulting in cardiac tissue that no longer performs efficiently.

Every year about 715,000 Americans have a heart attack. Of those, 525,000 are a first heart attack and 190,000 are repeat episodes. Every 44 seconds someone in the United States dies of a heart attack, according to federal data.

If stem cells can aid in the remodeling of the heart, regenerating healthy tissue, then medicine can offer patients a new lease on life, the doctors said.

Arriving at a point when such a treatment can be offered, Gruberg added, requires research. The gold standard of clinical study in Western medicine is the placebo-controlled randomized clinical trial, which means some of the Stony Brook heart patients will receive a stem cell transplant, others, a placebo.

Doctors began their study, part of a larger national investigation, abruptly late last month because they had been awaiting the perfect patient.

That person, a 66-year-old man who had been visiting Long Island from the Midwest, arrived at Stony Brook University Hospital as a transfer from Southampton Hospital.

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Stem-Cell Therapy and Repair after Heart Attack and Heart Failure

By raymumme

Stem Cell Therapy: Helping the Body Heal Itself

Stem cells are natures own transformers. When the body is injured, stem cells travel the scene of the accident. Some come from the bone marrow, a modest number of others, from the heart itself. Additionally, theyre not all the same. There, they may help heal damaged tissue. They do this by secreting local hormones to rescue damaged heart cells and occasionally turning into heart muscle cells themselves. Stem cells do a fairly good job. But they could do better for some reason, the heart stops signaling for heart cells after only a week or so after the damage has occurred, leaving the repair job mostly undone. The partially repaired tissue becomes a burden to the heart, forcing it to work harder and less efficiently, leading to heart failure.

Initial research used a patients own stem cells, derived from the bone marrow, mainly because they were readily available and had worked in animal studies. Careful study revealed only a very modest benefit, so researchers have moved on to evaluate more promising approaches, including:

No matter what you may read, stem cell therapy for damaged hearts has yet to be proven fully safe and beneficial. It is important to know that many patients are not receiving the most current and optimal therapies available for their heart failure. If you have heart failure, and wondering about treatment options, an evaluation or a second opinion at a Center of Excellence can be worthwhile.

Randomized clinical trials evaluating these different approaches typically allow enrollment of only a few patients from each hospital, and hence what may be available at the Cleveland Clinic varies from time to time. To inquire about current trials, please call 866-289-6911 and speak to our Resource Nurses.

Cleveland Clinic is a large referral center for advanced heart disease and heart failure we offer a wide range of therapies including medications, devices and surgery. Patients will be evaluated for the treatments that best address their condition. Whether patients meet the criteria for stem cell therapy or not, they will be offered the most advanced array of treatment options.

Reviewed: 04/13

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Stem cells – Dr Jekyll or Mr Hyde: Hans Clevers at TEDxAmsterdam – Video

By NEVAGiles23


Stem cells - Dr Jekyll or Mr Hyde: Hans Clevers at TEDxAmsterdam
Produced by: http://www.fellermedia.com Camera Crew: http://www.hoens.tv Stem cells are the foundation of all mammalian life, including that of man. Every ...

By: TEDxTalks

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MD Supervised Stem Cell Therapy

By daniellenierenberg

Regenerative medicine is the process of replacing or regenerating human cells, tissues or organs to restore or establish normal function.[1] This field holds the promise of regenerating damaged tissues and organs in the body by replacing damaged tissue and/or by stimulating the bodys own repair mechanisms to heal previously irreparable tissues or organs.

Regenerative medicine also includes the possibility of growing tissues and organs in the laboratory and safely implant them when the body cannot heal itself This can potentially solves the problem of the shortage of organs available for donation, and the problem of organ transplant rejection if the organs cells are derived from the patients own tissue or cells.[2][3][4]

Widely attributed to having first been coined by William Haseltine (founder of Human Genome Sciences),[5] the term Regenerative Medicine was first found in a 1992 article on hospital administration by Leland Kaiser. Kaisers paper closes with a series of short paragraphs on future technologies that will impact hospitals. One such paragraph had Regenerative Medicine as a bold print title and went on to state, A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems.[6][7]

Regenerative medicine refers to a group of biomedical approaches to clinical therapies that may involve the use of stem cells.[8] Examples include the injection of stem cells or progenitor cells (cell therapies); the induction of regeneration by biologically active molecules administered alone or as a secretion by infused cells (immunomodulation therapy); and transplantation of in vitro grown organs and tissues (Tissue engineering).[9][10]

A form of regenerative medicine that recently made it into clinical practice, is the use of heparan sulfate analogues on (chronic) wound healing. Heparan sulfate analogues replace degraded heparan sulfate at the wound site. They assist the damaged tissue to heal itself by repositioning growth factors and cytokines back into the damaged extracellular matrix.[11][12][13] For example, in abdominal wall reconstruction (like inguinal hernia repair), biologic meshes are being used with some success.

At the Wake Forest Institute for Regenerative Medicine, in North Carolina, Dr. Anthony Atala and his colleagues have successfully extracted muscle and bladder cells from several patients bodies, cultivated these cells in petri dishes, and then layered the cells in three-dimensional molds that resembled the shapes of the bladders. Within weeks, the cells in the molds began functioning as regular bladders which were then implanted back into the patients bodies.[14] The team is currently[when?] working on re-growing over 22 other different organs including the liver, heart, kidneys and testicles.[15]

From 1995 to 1998 Michael D. West, PhD, organized and managed the research between Geron Corporation and its academic collaborators James Thomson at the University of Wisconsin-Madison and John Gearhart of Johns Hopkins University that led to the first isolation of human embryonic stem and human embryonic germ cells.[16]

Dr. Stephen Badylak, a Research Professor in the Department of Surgery and director of Tissue Engineering at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, developed a process for scraping cells from the lining of a pigs bladder, decellularizing (removing cells to leave a clean extracellular structure) the tissue and then drying it to become a sheet or a powder. This cellular matrix powder was used to regrow the finger of Lee Spievak, who had severed half an inch of his finger after getting it caught in a propeller of a model plane.[17][18][19][dubious discuss] As of 2011, this new technology is being employed by the military to U.S. war veterans in Texas, as well as to some civilian patients. Nicknamed pixie-dust, the powdered extracellular matrix is being used success to regenerate tissue lost and damaged due to traumatic injuries.

In June 2008, at the Hospital Clnic de Barcelona, Professor Paolo Macchiarini and his team, of the University of Barcelona, performed the first tissue engineered trachea (wind pipe) transplantation. Adult stem cells were extracted from the patients bone marrow, grown into a large population, and matured into cartilage cells, or chondrocytes, using an adaptive method originally devised for treating osteoarthritis. The team then seeded the newly grown chondrocytes, as well as epithileal cells, into a decellularised (free of donor cells) tracheal segment that was donated from a 51 year old transplant donor who had died of cerebral hemorrhage. After four days of seeding, the graft was used to replace the patients left main bronchus. After one month, a biopsy elicited local bleeding, indicating that the blood vessels had already grown back successfully.[20][21]

In 2009 the SENS Foundation was launched, with its stated aim as the application of regenerative medicine defined to include the repair of living cells and extracellular material in situ to the diseases and disabilities of ageing. [22]

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Zaal Kokaia and Olle Lindvall – Stem cell therapy for stroke and other neurodegenerative diseases – Video

By raymumme


Zaal Kokaia and Olle Lindvall - Stem cell therapy for stroke and other neurodegenerative diseases
Interview wtth Zaal Kokaia and Olle Lindvall, researchers at Lund Stem Cell Center.

By: Medicinska Fakulteten, LU

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Stem Cell Stories trailer – Stem Cell Therapy Europe – Video

By LizaAVILA


Stem Cell Stories trailer - Stem Cell Therapy Europe
Stem Cell Stories trailer - Stem Cell Therapy Europe.

By: stemcelltherapy.eu

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What are adult stem cells? [Stem Cell Information]

By raymumme

Introduction: What are stem cells, and why are they important? What are the unique properties of all stem cells? What are embryonic stem cells? What are adult stem cells? What are the similarities and differences between embryonic and adult stem cells? What are induced pluripotent stem cells? What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized? Where can I get more information?

An adult stem cell is thought to be an undifferentiated cell, found among differentiated cells in a tissue or organ that can renew itself and can differentiate to yield some or all of the major specialized cell types of the tissue or organ. The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found. Scientists also use the term somatic stem cell instead of adult stem cell, where somatic refers to cells of the body (not the germ cells, sperm or eggs). Unlike embryonic stem cells, which are defined by their origin (cells from the preimplantation-stage embryo), the origin of adult stem cells in some mature tissues is still under investigation.

Research on adult stem cells has generated a great deal of excitement. Scientists have found adult stem cells in many more tissues than they once thought possible. This finding has led researchers and clinicians to ask whether adult stem cells could be used for transplants. In fact, adult hematopoietic, or blood-forming, stem cells from bone marrow have been used in transplants for 40 years. Scientists now have evidence that stem cells exist in the brain and the heart. If the differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of transplantation-based therapies.

The history of research on adult stem cells began about 50 years ago. In the 1950s, researchers discovered that the bone marrow contains at least two kinds of stem cells. One population, called hematopoietic stem cells, forms all the types of blood cells in the body. A second population, called bone marrow stromal stem cells (also called mesenchymal stem cells, or skeletal stem cells by some), were discovered a few years later. These non-hematopoietic stem cells make up a small proportion of the stromal cell population in the bone marrow, and can generate bone, cartilage, fat, cells that support the formation of blood, and fibrous connective tissue.

In the 1960s, scientists who were studying rats discovered two regions of the brain that contained dividing cells that ultimately become nerve cells. Despite these reports, most scientists believed that the adult brain could not generate new nerve cells. It was not until the 1990s that scientists agreed that the adult brain does contain stem cells that are able to generate the brain's three major cell typesastrocytes and oligodendrocytes, which are non-neuronal cells, and neurons, or nerve cells.

Adult stem cells have been identified in many organs and tissues, including brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, and testis. They are thought to reside in a specific area of each tissue (called a "stem cell niche"). In many tissues, current evidence suggests that some types of stem cells are pericytes, cells that compose the outermost layer of small blood vessels. Stem cells may remain quiescent (non-dividing) for long periods of time until they are activated by a normal need for more cells to maintain tissues, or by disease or tissue injury.

Typically, there is a very small number of stem cells in each tissue, and once removed from the body, their capacity to divide is limited, making generation of large quantities of stem cells difficult. Scientists in many laboratories are trying to find better ways to grow large quantities of adult stem cells in cell culture and to manipulate them to generate specific cell types so they can be used to treat injury or disease. Some examples of potential treatments include regenerating bone using cells derived from bone marrow stroma, developing insulin-producing cells for type1 diabetes, and repairing damaged heart muscle following a heart attack with cardiac muscle cells.

Scientists often use one or more of the following methods to identify adult stem cells: (1) label the cells in a living tissue with molecular markers and then determine the specialized cell types they generate; (2) remove the cells from a living animal, label them in cell culture, and transplant them back into another animal to determine whether the cells replace (or "repopulate") their tissue of origin.

Importantly, it must be demonstrated that a single adult stem cell can generate a line of genetically identical cells that then gives rise to all the appropriate differentiated cell types of the tissue. To confirm experimentally that a putative adult stem cell is indeed a stem cell, scientists tend to show either that the cell can give rise to these genetically identical cells in culture, and/or that a purified population of these candidate stem cells can repopulate or reform the tissue after transplant into an animal.

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What are adult stem cells? [Stem Cell Information]

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Autologous Stem Cell and Non-Stem Cell Based Therapies Market …

By Dr. Matthew Watson

Research and Markets Logo

DUBLIN, November 7, 2013 /PRNewswire/ --

Research and Markets ( http://www.researchandmarkets.com/research/l9klxc/autologous_stem) has announced the addition of the "Autologous Stem Cell and Non-Stem Cell Based Therapies Market (2012-2017) (Neurodegenerative, cardiovascular, cancer & autoimmune, skin and infectious diseases)" report to their offering.

(Logo: http://photos.prnewswire.com/prnh/20130307/600769 )

This research report titled Autologous Cell Therapy (2012-2017) provides details about various ACT based treatments and their application areas. Every health regulatory body will be expecting companies and universities to develop therapy treatments, which are safer, affordable, robust, rapid, easy to use, effective and deliverable to the end user. ACT treatments for particular application areas it is safe, experiencing robust growth, minimal steps of procedure to follow and rapid in deriving the results. As for now the treatments prices are not affordable, but by the intrusion of government bodies, it will definitely experience a immense market growth.

The report gives a detailed analysis about state of the art of autologous cell therapies. It includes the current advances and applications of the technology and trends in terms of market size and growth of autologous cellular therapies in medical treatments globally. It also consists of funding details of the innovative therapy and recent activities in terms of mergers & acquisitions of the company, revenue forecasting. It includes latest therapy details and products which are available for licensing and approvals from various regulatory bodies. Using drivers, restraints and challenges it is forecasted for a period of five years i.e. 2012-2017. Opportunity strategy evaluation has been included which gives information for investors.

Autologous Cell Therapy technology is changing the medicinal treatments by introducing various new therapies. Its scope is vast and promising for the future despite challenges.

Key Topics Covered:

1 Introduction 2 Executive Summary 3 Autologous Cell Therapy (Act)-Technology Landscape Analysis 4 Technology Investment Potential 5 Market Landscape Analysis 6 Act - Technology Adoption Potential And Development By Geography 7 Competitive Landscape 8 Patent Analysis 9 Technology Analysis And Road Mapping 10 Analyst Insights And Recommendations 11 Company Profiles 12 Appendix 13 Glossary

Companies Mentioned

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Skin stem cells: where do they live and what can they do? | Europe …

By NEVAGiles23

The skin

In humans and other mammals, the skin has three parts - the epidermis, the dermis and the subcutis (or hypodermis). The epidermis forms the surface of the skin. It is made up of several layers of cells called keratinocytes. The dermis lies underneath the epidermis and contains skin appendages: hair follicles, sebaceous (oil) glands and sweat glands. The subcutis contains fat cells and some sweat glands.

The skin and its structure: The skin has three main layers - the epidermis, dermis and subcutis. The epidermis contains layers of cells called keratinocytes. BL = basal layer; SL = spinous layer; GL = granular layer; SC= stratum corneum. Image adapted by permission from Macmillan Publishers Ltd: Nature Reviews Genetics 3, 199-209 (March 2002), Getting under the skin of epidermal morphogenesis, Elaine Fuchs & Srikala Raghavan; doi:10.1038/nrg758; Copyright 2002.

In everyday life your skin has to cope with a lot of wear and tear. For example, it is exposed to chemicals like soap and to physical stresses such as friction with your clothes or exposure to sunlight. The epidermis and skin appendages need to be renewed constantly to keep your skin in good condition. Whats more, if you cut or damage your skin, it has to be able to repair itself efficiently to keep doing its job protecting your body from the outside world.

Skin stem cells make all this possible. They are responsible for constant renewal (regeneration) of your skin, and for healing wounds. So far, scientists have identified several different types of skin stem cell:

Some studies have also suggested that another type of stem cell, known as mesenchymal stem cells, can be found in the dermis and hypodermis. This remains controversial amongst scientists and further studies are needed to determine whether these cells are truly mesenchymal stem cells and what their role is in the skin.

Epidermal stem cells are one of the few types of stem cell already used to treat patients. Thanks to a discovery made in 1970 by Professor Howard Green in the USA, epidermal stem cells can be taken from a patient, multiplied and used to grow sheets of epidermis in the lab. The new epidermis can then be transplanted back onto the patient as a skin graft. This technique is mainly used to save the lives of patients who have third degree burns over very large areas of their bodies. Only a few clinical centres are able to carry out the treatment successfully, and it is an expensive process. It is also not a perfect solution. Only the epidermis can be replaced with this method; the new skin has no hair follicles, sweat glands or sebaceous glands.

One of the current challenges for stem cell researchers is to understand how all the skin appendages are regenerated. This could lead to improved treatments for burn patients, or others with severe skin damage.

Researchers are also working to identify new ways to grow skin cells in the lab. Epidermal stem cells are currently cultivated on a layer of cells from rodents, called murine cells. These cell culture conditions have been proved safe, but it would be preferable to avoid using animal products when cultivating cells that will be transplanted into patients. So, researchers are searching for effective cell culture conditions that will not require the use of murine cells.

Scientists are also working to treat genetic diseases affecting the skin. Since skin stem cells can be cultivated in laboratories, researchers can genetically modify the cells, for example by inserting a missing gene. The correctly modified cells can be selected, grown and multiplied in the lab, then transplanted back onto the patient. Epidermolysis Bullosa is one example of a genetic skin disease that might benefit from this approach. Work is underway to test the technique.

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IPS Cell Therapy – Genetherapy

By LizaAVILA

In 2006, Shinya Yamanaka of Kyoto University in Japan was the first to disprove the previous notion that reversible cell differentiation of mammals was impossible. He reprogrammed a fully differentiated mouse cell into a pluripotent stem cell by introducing four genes, Oct-4, SOX2, KLF4, and Myc, into the mouse fibroblast through gene-carrying viruses. With this method, he and his coworkers created induced pluripotent stem cells (iPS cells), the key component in this experiment.[1] Scientists have been able to conduct experiments that show the ability of iPS cells to treat and even cure diseases. In this experiment, tests were run on mice with inherited sickle cell anemia.Skin cells were turned into cells containing genes that transformed the cells into iPS cells. These replaced the diseased sickled cells, curing the test mice. The reprogramming of the pluripotent stem cells in mice was successfully duplicated with human pluripotent stem cells within about a year of the experiment on the mice.

Sickle cell anemia is a disease in which the body produces abnormally shaped red blood cells. Red blood cells are flexible and round, moving easily through the blood vessels. Infected cells are shaped like a crescent or sickle (the namesake of the disease). As a result of this disorder the hemoglobin protein in red blood cells is faulty. Normal hemoglobin bonds to oxygen, then releases it into cells that need it. The blood cell retains its original form and is cycled back to the lungs and re-oxygenated.

Sickle cell hemoglobin, however, after giving up oxygen, cling together and make the red blood cell stiff. The sickle shape also makes it difficult for the red blood cell to navigate arteries and causes blockages.[2] This can cause intense pain and organ damage. The sickled red blood cells are fragile and prone to rupture. When the number of red blood cells decreases from rupture (hemolysis), anemia is the result. Sickle cells also die in 1020 days as opposed to the traditional 120-day lifespan of a normal red blood cell.

Sickle cell anemia is inherited as an autosomal (meaning that the gene is not linked to a sex chromosome) recessive condition.[2] This means that the gene can be passed on from a carrier to his or her children. In order for sickle cell anemia to affect a person, the gene must be inherited from both the mother and the father, so that the child has two recessive sickle cell genes (a homozygous inheritance). People who inherit one sickle cell gene from one parent and one normal gene from the other parent, i.e. heterozygous patients, have a condition called sickle cell trait. Their bodies make both sickle hemoglobin and normal hemoglobin. They may pass the trait on to their children.

The effects of sickle cell anemia vary from person to person. People who have the disease suffer from varying degrees of chronic pain and fatigue. With proper care and treatment, the quality of health of most patients will improve. Doctors have learned a great deal about sickle cell anemia since its discovery in 1979. They know its causes, its effects on the body, and possible treatments for complications. Sickle cell anemia has no widely available cure. A bone marrow transplant is the only treatment method currently recognized to be able to cure the disease, though it does not work for every patient. Finding a donor is difficult and the procedure could potentially do more harm than good. Treatments for sickle cell anemia are generally aimed at avoiding crises, relieving symptoms, and preventing complications. Such treatments may include medications, blood transfusions, and supplemental oxygen.

During the first step of the experiment, skin cells (also known as fibroblasts) were collected from infected test mice and put in a culture. The fibroblasts were reprogrammed by infecting them with retroviruses that contained genes common to embryonic stem cells. These genes were the same four used by Yamanaka (Oct-4, SOX2, KLF4, and Myc) in his earlier study. The investigators were trying to produce cells with the potential to differentiate into any type of cell needed (i.e. pluripotent stem cells). As the experiment continued, the fibroblasts multiplied into identical copies of iPS cells. The cells were then treated to form the mutation needed to reverse the anemia in the mice. This was accomplished by restructuring the DNA containing the defective globin gene into DNA with the normal gene through the process of homologous recombination. The iPS cells then differentiated into blood stem cells, or hematopoietic stem cells. The hematopoietic cells were injected back into the infected mice, where they proliferate and differentiate into normal blood cells, curing the mice of the disease.[3][4][verification needed]

To determine whether the mice were cured from the disease, the scientists checked for the usual symptoms of sickle cell disease. They examined the blood for mean corpuscular volume (MCV) and red cell distribution width (RDW) and urine concentration defects. They also checked for sickled red blood cells. They examined the DNA through gel electrophoresis, checking for bands that display an allele that causes sickling. Compared to the untreated mice with the disease, which they used as a control, the treated animals had marked increases in RBC counts, healthy hemoglobin, and packed cell volume levels.[5]

Researchers examined the urine concentration defect, which results from RBC sickling in renal tubules and consequent reduction in renal medullary blood flow, and the general deteriorated systemic condition reflected by lower body weight and increased breathing.[5] They were able to see that these parts of the body of the mice had healed or improved. This indicated that all hematological and systemic parameters of sickle cell anemia improved substantially and were comparable to those in control mice.[5] They cannot say if this will work in humans because a safe way to inject the genes for the induced pluripotent cells is still needed.[citation needed]

The reprogramming of the induced pluripotent stem cells in mice was successfully duplicated in humans within a year of the successful experiment on the mice. This reprogramming was done in several labs and it was shown that the iPS cells in humans were almost identical to original embryonic stem cells (ES cells) that are responsible for the creation of all structures in a fetus.[1] An important feature of iPS cells is that they can be generated with cells taken from an adult, which would circumvent many of the ethical problems associated with working with ES cells. These iPS cells also have potential in creating and examining new disease models and developing more efficient drug treatments.[6] Another feature of these cells is that they provide researchers with a human cell sample, as opposed to simply using an animal with similar DNA, for drug testing.

One major problem with iPS cells is the way in which the cells are reprogrammed. Using gene-carrying viruses has the potential to cause iPS cells to develop into cancerous cells.[1] Also, an implant made using undifferentiated iPS cells, could cause a teratoma to form. Any implant that is generated from using these iPS cells would only be viable for transplant into the original subject that the cells were taken from. In order for these iPS cells to become viable in therapeutic use, there are still many steps that must be taken.[5][7]

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Induced pluripotent stem cell therapy – Wikipedia, the free …

By Sykes24Tracey

In 2006, Shinya Yamanaka of Kyoto University in Japan was the first to disprove the previous notion that reversible cell differentiation of mammals was impossible. He reprogrammed a fully differentiated mouse cell into a pluripotent stem cell by introducing four genes, Oct-4, SOX2, KLF4, and Myc, into the mouse fibroblast through gene-carrying viruses. With this method, he and his coworkers created induced pluripotent stem cells (iPS cells), the key component in this experiment.[1] Scientists have been able to conduct experiments that show the ability of iPS cells to treat and even cure diseases. In this experiment, tests were run on mice with inherited sickle cell anemia.Skin cells were turned into cells containing genes that transformed the cells into iPS cells. These replaced the diseased sickled cells, curing the test mice. The reprogramming of the pluripotent stem cells in mice was successfully duplicated with human pluripotent stem cells within about a year of the experiment on the mice.

Sickle cell anemia is a disease in which the body produces abnormally shaped red blood cells. Red blood cells are flexible and round, moving easily through the blood vessels. Infected cells are shaped like a crescent or sickle (the namesake of the disease). As a result of this disorder the hemoglobin protein in red blood cells is faulty. Normal hemoglobin bonds to oxygen, then releases it into cells that need it. The blood cell retains its original form and is cycled back to the lungs and re-oxygenated.

Sickle cell hemoglobin, however, after giving up oxygen, cling together and make the red blood cell stiff. The sickle shape also makes it difficult for the red blood cell to navigate arteries and causes blockages.[2] This can cause intense pain and organ damage. The sickled red blood cells are fragile and prone to rupture. When the number of red blood cells decreases from rupture (hemolysis), anemia is the result. Sickle cells also die in 1020 days as opposed to the traditional 120-day lifespan of a normal red blood cell.

Sickle cell anemia is inherited as an autosomal (meaning that the gene is not linked to a sex chromosome) recessive condition.[2] This means that the gene can be passed on from a carrier to his or her children. In order for sickle cell anemia to affect a person, the gene must be inherited from both the mother and the father, so that the child has two recessive sickle cell genes (a homozygous inheritance). People who inherit one sickle cell gene from one parent and one normal gene from the other parent, i.e. heterozygous patients, have a condition called sickle cell trait. Their bodies make both sickle hemoglobin and normal hemoglobin. They may pass the trait on to their children.

The effects of sickle cell anemia vary from person to person. People who have the disease suffer from varying degrees of chronic pain and fatigue. With proper care and treatment, the quality of health of most patients will improve. Doctors have learned a great deal about sickle cell anemia since its discovery in 1979. They know its causes, its effects on the body, and possible treatments for complications. Sickle cell anemia has no widely available cure. A bone marrow transplant is the only treatment method currently recognized to be able to cure the disease, though it does not work for every patient. Finding a donor is difficult and the procedure could potentially do more harm than good. Treatments for sickle cell anemia are generally aimed at avoiding crises, relieving symptoms, and preventing complications. Such treatments may include medications, blood transfusions, and supplemental oxygen.

During the first step of the experiment, skin cells (also known as fibroblasts) were collected from infected test mice and put in a culture. The fibroblasts were reprogrammed by infecting them with retroviruses that contained genes common to embryonic stem cells. These genes were the same four used by Yamanaka (Oct-4, SOX2, KLF4, and Myc) in his earlier study. The investigators were trying to produce cells with the potential to differentiate into any type of cell needed (i.e. pluripotent stem cells). As the experiment continued, the fibroblasts multiplied into identical copies of iPS cells. The cells were then treated to form the mutation needed to reverse the anemia in the mice. This was accomplished by restructuring the DNA containing the defective globin gene into DNA with the normal gene through the process of homologous recombination. The iPS cells then differentiated into blood stem cells, or hematopoietic stem cells. The hematopoietic cells were injected back into the infected mice, where they proliferate and differentiate into normal blood cells, curing the mice of the disease.[3][4][verification needed]

To determine whether the mice were cured from the disease, the scientists checked for the usual symptoms of sickle cell disease. They examined the blood for mean corpuscular volume (MCV) and red cell distribution width (RDW) and urine concentration defects. They also checked for sickled red blood cells. They examined the DNA through gel electrophoresis, checking for bands that display an allele that causes sickling. Compared to the untreated mice with the disease, which they used as a control, the treated animals had marked increases in RBC counts, healthy hemoglobin, and packed cell volume levels.[5]

Researchers examined the urine concentration defect, which results from RBC sickling in renal tubules and consequent reduction in renal medullary blood flow, and the general deteriorated systemic condition reflected by lower body weight and increased breathing.[5] They were able to see that these parts of the body of the mice had healed or improved. This indicated that all hematological and systemic parameters of sickle cell anemia improved substantially and were comparable to those in control mice.[5] They cannot say if this will work in humans because a safe way to inject the genes for the induced pluripotent cells is still needed.[citation needed]

The reprogramming of the induced pluripotent stem cells in mice was successfully duplicated in humans within a year of the successful experiment on the mice. This reprogramming was done in several labs and it was shown that the iPS cells in humans were almost identical to original embryonic stem cells (ES cells) that are responsible for the creation of all structures in a fetus.[1] An important feature of iPS cells is that they can be generated with cells taken from an adult, which would circumvent many of the ethical problems associated with working with ES cells. These iPS cells also have potential in creating and examining new disease models and developing more efficient drug treatments.[6] Another feature of these cells is that they provide researchers with a human cell sample, as opposed to simply using an animal with similar DNA, for drug testing.

One major problem with iPS cells is the way in which the cells are reprogrammed. Using gene-carrying viruses has the potential to cause iPS cells to develop into cancerous cells.[1] Also, an implant made using undifferentiated iPS cells, could cause a teratoma to form. Any implant that is generated from using these iPS cells would only be viable for transplant into the original subject that the cells were taken from. In order for these iPS cells to become viable in therapeutic use, there are still many steps that must be taken.[5][7]

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Induced pluripotent stem cell therapy - Wikipedia, the free ...

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Human muscle stem cell therapy gets help from zebrafish

By daniellenierenberg

PUBLIC RELEASE DATE:

7-Nov-2013

Contact: B. D. Colen bd_colen@harvard.edu 617-495-7821 Harvard University

Harvard Stem Cell Scientists have discovered that the same chemicals that stimulate muscle development in zebrafish can also be used to differentiate human stem cells into muscle cells in the laboratory, an historically challenging task that, now overcome, makes muscle cell therapy a more realistic clinical possibility.

The work, published this week in the journal Cell, began with a discovery by Boston Children's Hospital researchers, led by Leonard Zon, MD, and graduate student Cong (Tony) Xu, who tested 2,400 different chemicals in cultures of zebrafish embryo cells to determine if any could increase the numbers of muscle cells formed. Using fluorescent reporter fish in which muscle cells were visible during their creation, the researchers found six chemicals that were very effective at promoting muscle formation.

Zon shared his results with Harvard Department of Stem Cell and Regenerative Biology professor Amy Wagers, PhD, and Mohammadsharif Tabebordbar, a graduate student in her laboratory, who tested the six chemicals in mice. One of the six, called forskolin, was found to increase the numbers of muscle stem cells from mice that could be obtained when these cells were grown in laboratory dishes. Moreover, the cultured cells successfully integrated into muscle when transplanted back into mice.

Inspired by the successful application of these chemicals in mice, Salvatore Iovino, PhD, a joint postdoctoral fellow in the Wagers lab and the lab of C. Ronald Kahn, MD, at the Joslin Diabetes Center, investigated whether the chemicals would also affect human cells and found that a combination of three chemicals, including forskolin, could induce differentiation of human induced pluripotent stem (iPS) cells, made by reprogramming skin cells. Exposure of iPS cells to these chemicals converted them into skeletal muscle, an outcome the Wagers and Kahn labs had been striving to achieve for years using conventional methods. When transplanted into a mouse, the human iPS-derived muscle cells also contributed to muscle repair, offering early promise that this protocol could provide a route to muscle stem cell therapy in humans.

The interdisciplinary, cross-laboratory collaboration between Zon, Wagers, and Kahn highlights the advantage of open exchange between researchers. "If we had done this screen directly on human iPS cells, it would have taken at least 10 times as long and cost 100 times as much," said Wagers. "The zebrafish gave us a big advantage here because it has a fast generation time, rapid development, and can be easily and relatively cheaply screened in a culture dish."

"This research demonstrates that over 300 million years of evolution, the pathways used in the fish are conserved through vertebrates all the way up to the human," said Wagers' fellow HSCRB professor Leonard Zon, chair of the Harvard Stem Cell Institute Executive Committee and director of the stem cell program at Boston Children's Hospital. "We can now make enough human muscle progenitors in a dish to allow us to model diseases of the muscle lineage, like Duchenne muscular dystrophy, conduct drug screens to find chemicals that correct those disease, and in the long term, efficiently transplant muscle stem cells into a patient."

In a similar biomedical application, Kahn, who is chief academic officer at the Joslin, plans to apply the new ability to quickly produce muscle stem cells for diabetes research. His lab will generate iPS-derived muscle cells from people who are at risk for diabetes and people who have diabetes to identify alterations that lead to insulin resistance in the muscle.

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Human muscle stem cell therapy gets help from zebrafish

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