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Stem Cells Edited to Fight Arthritis Technology Networks Such stem cells, known as SMART cells (Stem cells Modified for Autonomous Regenerative Therapy), develop into cartilage cells that produce a biologic anti-inflammatory drug that, ideally, will replace arthritic cartilage and simultaneously protect ... CRISPR-SMART Cells Regenerate Cartilage, Secrete Anti-Arthritis DrugGenetic Engineering & Biotechnology News all 5 news articles »

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Stem Cells Edited to Fight Arthritis - Technology Networks

Skin Stem Cells Comments Off on Stem Cells Edited to Fight Arthritis – Technology Networks | April 28th, 2017

The DMC reviewed all of the accumulated safety data to date. The review included the safety data from six complete cervical injury (AIS-A) patients dosed with 10 million AST-OPC1 cells in Cohort 2, each of whom have completed at least six months of follow-up, as well as initial safety data from the currently enrolling Cohorts 3 and 4. Cohort 3 is enrolling AIS-A patients dosed with the highest dose of 20 million cells; Cohort 4 is testing 10 million cells in patients with less severe AIS-B incomplete cervical spinal cord injuries. In addition, the DMC reviewed the ongoing long-term safety data from the study's initial cohort of three patients dosed with 2 million cells, all of whom completed 12 months of follow-up in 2016.

As specified in the SCiStar study protocol, the DMC meets on a regular basis to review data from the ongoing trial. The DMC is comprised of an independent group of medical and scientific experts and is responsible for reviewing and evaluating patient safety and efficacy data for safeguarding the interest of study participants.

Asterias previously reported on positive early efficacy data from Cohort 2 (AIS-A; 10 million cells) of the SCiStar study. Patients from this cohort showed improvement in upper extremity motor function at 3-months following administration of AST-OPC1 and maintained or further increased this improvement at 6-months and 9-months. The results suggest a meaningful and favorable difference to date in recovery of arm, hand and finger function in patients treated with the 10 million cell dose of AST-OPC1 as compared to the level of expected rates of spontaneous recovery shown from historical control data of a closely matched patient population. Asterias expects to report additional efficacy and safety data for Cohort 2, as well as for the currently-enrolling Cohorts 3 and 4, later this year.

About the SCiStar Trial

The SCiStar trial is an open-label, single-arm trial testing three sequential escalating doses of AST-OPC1 administered at up to 20 million AST-OPC1 cells in as many as 35 patients with sub-acute, C-5 to C-7, motor complete (AIS-A or AIS-B) cervical SCI. These individuals have essentially lost all movement below their injury site and experience severe paralysis of the upper and lower limbs. AIS-A patients have lost all motor and sensory function below their injury site, while AIS-B patients have lost all motor function but may retain some minimal sensory function below their injury site. AST-OPC1 is being administered 14 to 30 days post-injury. Patients will be followed by neurological exams and imaging procedures to assess the safety and activity of the product.

The study is being conducted at six centers in the U.S. and the company plans to increase this to up to 12 sites to accommodate the expanded patient enrollment. Clinical sites involved in the study include the Medical College of Wisconsin in Milwaukee, Shepherd Medical Center in Atlanta, University of Southern California (USC) jointly with Rancho Los Amigos National Rehabilitation Center in Los Angeles, Indiana University, Rush University Medical Center in Chicago and Santa Clara Valley Medical Center in San Jose jointly with Stanford University.

Asterias has received a Strategic Partnerships Award grant from the California Institute for Regenerative Medicine, which provides $14.3 million of non-dilutive funding for the Phase 1/2a clinical trial and other product development activities for AST-OPC1.

Additional information on the Phase 1/2a trial, including trial sites, can be found at http://www.clinicaltrials.gov, using Identifier NCT02302157, and at the SCiStar Study Website (www.SCiStar-study.com).

About AST-OPC1

AST-OPC1, an oligodendrocyte progenitor population derived from human embryonic stem cells, has been shown in animals and in vitro to have three potentially reparative functions that address the complex pathologies observed at the injury site of a spinal cord injury. These activities of AST-OPC1 include production of neurotrophic factors, stimulation of vascularization, and induction of remyelination of denuded axons, all of which are critical for survival, regrowth and conduction of nerve impulses through axons at the injury site. In preclinical animal testing, AST-OPC1 administration led to remyelination of axons, improved hindlimb and forelimb locomotor function, dramatic reductions in injury-related cavitation and significant preservation of myelinated axons traversing the injury site.

In a previous Phase 1 clinical trial, five patients with neurologically complete, thoracic spinal cord injury were administered two million AST-OPC1 cells at the spinal cord injury site 7-14 days post-injury. They also received low levels of immunosuppression for the next 60 days. Delivery of AST-OPC1 was successful in all five subjects with no serious adverse events associated with AST-OPC1. No evidence of rejection of AST-OPC1 was observed in detailed immune response monitoring of all patients. In four of the five patients, serial MRI scans indicated that reduced spinal cord cavitation may have occurred. Based on the results of this study, Asterias received clearance from FDA to progress testing of AST-OPC1 to patients with complete cervical spine injuries, which represents the first targeted population for registration trials.

About Asterias Biotherapeutics

Asterias Biotherapeutics, Inc. is a biotechnology company pioneering the field of regenerative medicine. The company's proprietary cell therapy programs are based on its pluripotent stem cell and immunotherapy platform technologies. Asterias is presently focused on advancing three clinical-stage programs which have the potential to address areas of very high unmet medical need in the fields of neurology and oncology. AST-OPC1 (oligodendrocyte progenitor cells) is currently in a Phase 1/2a dose escalation clinical trial in spinal cord injury. AST-VAC1 (antigen-presenting autologous dendritic cells) is undergoing continuing development by Asterias based on promising efficacy and safety data from a Phase 2 study in Acute Myeloid Leukemia (AML), with current efforts focused on streamlining and modernizing the manufacturing process. AST-VAC2 (antigen-presenting allogeneic dendritic cells) represents a second generation, allogeneic cancer immunotherapy. The company's research partner, Cancer Research UK, plans to begin a Phase 1/2a clinical trial of AST-VAC2 in non-small cell lung cancer in 2017. Additional information about Asterias can be found at http://www.asteriasbiotherapeutics.com.

FORWARD-LOOKING STATEMENTS

Statements pertaining to future financial and/or operating and/or clinical research results, future growth in research, technology, clinical development, and potential opportunities for Asterias, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the businesses of Asterias, particularly those mentioned in the cautionary statements found in Asterias' filings with the Securities and Exchange Commission. Asterias disclaims any intent or obligation to update these forward-looking statements.

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/asterias-biotherapeutics-announces-data-monitoring-committee-unanimously-recommends-continuation-of-scistar-phase-12a-clinical-trial-of-ast-opc1-for-cervical-spinal-cord-injury-300444644.html

SOURCE Asterias Biotherapeutics, Inc.

http://www.asteriasbiotherapeutics.com

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Asterias Biotherapeutics Announces Data Monitoring Committee Unanimously Recommends Continuation of SCiStar ... - PR Newswire (press release)

Spinal Cord Stem Cells Comments Off on Asterias Biotherapeutics Announces Data Monitoring Committee Unanimously Recommends Continuation of SCiStar … – PR Newswire (press release) | April 27th, 2017

Piero Anversa

Brigham and Womens Hospital and its parent healthcare network have agreed to pay $10 million to the U.S. government to resolve allegations it fraudulently obtained federal funding.

The case, which involves three former Harvard stem cell researchers, dates back several years. In 2014, Circulation retracted a paper by Piero Anversa, Annarosa Leri, and Jan Kajstura, among others, amidst a university investigation into misconduct allegations. Anversa and Leri whose lab was described as filled with fear by one former research fellow later sued the hospital for notifying journals of that investigation. They lost.

In the agreement announced today by the Department of Justice (DOJ), Partners Healthcare and Brigham and Womens Hospital have agreed to pay the government $10 million to settle allegations that the researchers fraudulently obtained funding from the National Institutes of Health:

The settlement resolves allegations that Dr. Anversa, along with Dr. Annarosa Leri and Dr. Jan Kajstura, knew or should have known that their laboratory promulgated and relied upon manipulated and falsified information, including confocal microscope images and carbon-14 age data for cells, in applications submitted for NIH research grant awards concerning the purported ability of stem cells to repair damage to the heart. The government alleges that problems with the work of the laboratory included improper protocols, invalid and inaccurately characterized cardiac stem cells, reckless or deliberately misleading record-keeping, and discrepancies and/or fabrication of data and images included in applications and publications. The government contends that, at the direction of these BWH scientists, the Anversa laboratory included false scientific information in claims to NIH in order to obtain and use funds from NIH grants.

John Thomas, a partner with Gentry Locke who represents whistleblowers who raise allegations of misconduct, told us that other cases have settled for large amounts such as a recent settlement with Columbia University for $9.5 million. But there are other elements that make this latest announcement noteworthy, he said.

Specifically, most settlements involve some black and white failure in research administration, such as misrepresenting a researchers qualifications on a grant, misreporting effort, or conducting the research at a different facility (such as the Columbia case), said Thomas. The latest decision, in contrast, goes to the science itself.

As a result, he said:

This demonstrates the government is still willing to step in even when its not an administrative issue, even when it goes to the merits of the actual misconduct allegations. I think it shows that when the government awards grants, one of the things its intending to get is good and honest science. The science matters.

We reached out to Anversa and Levi; in response, we received a statement from their attorney:

It is outrageous that BWH has sought to unfairly tarnish the reputations of Drs Anversa and Leri, scientists who have pioneered groundbreaking work in cardiac stem cell reproduction and who have litigation pending against BWH and its president, Betsy Nabel.

Neither Dr. Anversa nor Dr. Leri was involved in the settlement process. BWH self-reported allegations in its own way for its own purposes. It has long been known that Drs. Anversa and Leri relied on the work of a senior scientist in the lab in presenting data for grants and in publications. No one has ever shown that either Dr. Anversa or Dr. Leri participated in the fraud or was aware of it at the time.

BWHs allegations and settlement cannot take away from Drs. Anversa and Leris contributions to the science of stem cell replication. There are Phase II trials being conducted by NIH currently on stem cell treatments based on their work. Taxpayer money was rightly used to further the fight against heart disease, a leading cause of death in this country.

According to the U.S. Attorneys Office, Brigham and Womens Hospital brought the allegations to the governments attention:

After learning of the allegations of research misconduct in the Anversa laboratory, BWH investigated the allegations, disclosed its concerns to the U.S. Department of Health and Human Services, Office of the Inspector General (OIG) and Office of Research Integrity, and then worked cooperatively with OIG and the Department of Justice to explain the bases for the allegations.

The three researchers Anversa, Leri, and Kajstura are no longer based at Brigham and Womens Hospital. Earlier this year, Anversa and Leri published a paper about cardiac progenitor cells that lists an affiliation at the Swiss Institute for Regenerative Medicine.

In todays statement, Acting U.S. Attorney William D. Weinreb said:

Individuals and institutions that receive research funding from NIH have an obligation to conduct their research honestly and not to alter results to conform with unproven hypotheses.

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Harvard teaching hospital to pay $10 million to settle research misconduct allegations - Retraction Watch (blog)

Cardiac Stem Cells Comments Off on Harvard teaching hospital to pay $10 million to settle research misconduct allegations – Retraction Watch (blog) | April 27th, 2017

The patches may be effective at helping to restore the heart following a myocardial infarction, as the heart isnt able to restore lost cells on its own. The patches may be effective at helping to restore the heart following a myocardial infarction, as the heart isnt able to restore lost cells on its own.

A team of researchers from University of Minnesota-Twin Cities, University of Wisconsin-Madison, and University of Alabama-Birmingham have developed a technique for 3D printing cardiac patches seeded with living cells. The patches may be effective at helping to restore the heart following a myocardial infarction, as the heart isnt able to restore lost cells on its own.

The technology has already been tested on a mouse model following an induced heart attack in which cardiac function wa significantly improved in four weeks following the application of the patch.

The patch is structurally based on how proteins naturally assemble within cardiac tissue. A highly detailed technique called multiphoton-excited 3D printing was used to create an extracellular matrix that was then seeded with about 50,000 cardiomyocytes, smooth muscle cells, and endothelial cells obtained from human-induced pluripotent stem cells.

The patch began beating on its own only a day after placing the cells and calcium transients, which are intercellular signaling mechanisms, were detected and increased over the following week.

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3D Printed Patches seeded with cells to repair cardiac tissue after heart attacks - BSA bureau (press release)

Cardiac Stem Cells Comments Off on 3D Printed Patches seeded with cells to repair cardiac tissue after heart attacks – BSA bureau (press release) | April 27th, 2017

Source: Shutterstock.com

Researchers have showncertain cardiac glycosides can reduce hepatocyte production of aprecursor of LDL cholesterol.

Familial hypercholesterolaemia (FH) is a rare genetic disease that affects the production of functioning low-density lipoprotein (LDL) receptors in the liver. When patients have mutations in both copies of the LDL receptor gene, they do not respond to statins and have limited pharmaceutical treatment options available because of a lack of accurate disease models.

Reporting in Cell Stem Cell on 6 April 2017[1], researchers used FH human hepatocytes derived from induced pluripotent stem cells to screen for existing drugs that might lower apolipoprotein B (apoB) a precursor of LDL cholesterol.

The team found that all nine cardiac glycosides in their drug library reduced levels of apoB in the hepatocytes. In an analysis of historical patient data, the researchers found a reduction in serum LDL-C comparable to that seen with statins in patients taking cardiac glycosides.

The researchers say the results demonstrate the potential of their stem-cell based approach for identifying new treatment candidates for inherited liver diseases.

Citation: Clinical Pharmacist, CP April 2017 online, online | DOI: 10.1211/CP.2017.20202623

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Stem-cell screening finds statin alternative for hypercholesterolaemia - The Pharmaceutical Journal

Cardiac Stem Cells Comments Off on Stem-cell screening finds statin alternative for hypercholesterolaemia – The Pharmaceutical Journal | April 27th, 2017

SOUTH SAN FRANCISCO, CA--(Marketwired - April 27, 2017) - VistaGen Therapeutics Inc. (VTGN), a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders, announced today the peer-reviewed publication of nonclinical studies of the effects of AV-101 (4-Cl-KYN), its CNS prodrug candidate, in four well-established nonclinical models of pain.

The publication, titled: "Characterization of the effects of L-4-chlorokynurenine on nociception in rodents," by lead author, Tony L. Yaksh, Ph.D., and co-authors, Robert Schwarcz, Ph.D. and H. Ralph Snodgrass, Ph.D., was recently published in The Journal of Pain (DOI: 10.1016/j.jpain.2017.03.014) and is available online at http://www.jpain.org/article/S1526-5900(17)30552-7/abstract.

"In these studies, AV-101 was found to have robust anti-nociceptive effects, similar to gabapentin, but with a better side effect profile in several pre-clinical models of hyperalgesia and allodynia, results suggest AV-101's potential for treating multiple hyperpathic pain states," reported Tony L. Yaksh, Ph.D., Professor in Anesthesiology at the University of California, San Diego (UCSD).

"In comparison to gabapentin and other agents commonly used by millions of patients battling chronic neuropathic pain, we believe AV-101 has the potential to reduce debilitating pain effectively without causing burdensome side effects. Many neuropathic pain treatments on the market today have side effects, including anxiety, depression, mild cognitive impairment and sedation. The positive results published in these studies fall in line with our goal of advancing Phase 2 clinical development of AV-101 across a broad range of CNS indications, including major depressive disorder, neuropathic pain and L-DOPA-induced dyskinesia associated with Parkinson's disease. We are optimistic that we will be able to bring to market a new generation CNS medication that would help millions of patients currently treated with therapies with inadequate efficacy and significant side effects and safety concerns," stated H. Ralph Snodgrass, Ph.D., VistaGen's President and Chief Scientific Officer.

Study Summary and Key Findings:

About AV-101

AV-101 (4-CI-KYN) is an oral CNS prodrug candidate in Phase 2 development in the U.S. as a new generation treatment for major depressive disorder (MDD). AV-101 also has broad potential utility in several other CNS disorders, including chronic neuropathic pain and epilepsy, as well as addressing symptoms associated with neurodegenerative diseases, such as Parkinson's disease and Huntington's disease.

AV-101 is currently being evaluated in a Phase 2 monotherapy study in MDD, a study being fully funded by the U.S. National Institute of Mental Health (NIMH) and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH, as Principal Investigator.

VistaGen is preparing to advance AV-101 into a 180-patient, U.S. multi-center, Phase 2 adjunctive treatment study in MDD patients with an inadequate response to standard FDA-approved antidepressants, with Dr. Maurizio Fava of Harvard University as Principal Investigator.

About VistaGen

VistaGen Therapeutics, Inc. (VTGN), is a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders. VistaGen's lead CNS product candidate, AV-101, is in Phase 2 development as a new generation oral antidepressant drug candidate for major depressive disorder (MDD). AV-101's mechanism of action is fundamentally differentiated from all FDA-approved antidepressants and atypical antipsychotics used adjunctively to treat MDD, with potential to drive a paradigm shift towards a new generation of safer and faster-acting antidepressants. AV-101 is currently being evaluated by the U.S. National Institute of Mental Health (NIMH) in a Phase 2 monotherapy study in MDD being fully funded by the NIMH and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH. VistaGen is preparing to launch a 180-patient Phase 2 study of AV-101 as an adjunctive treatment for MDD patients with inadequate response to standard, FDA-approved antidepressants. Dr. Maurizio Fava of Harvard University will be the Principal Investigator of the Company's Phase 2 adjunctive treatment study. AV-101 may also have the potential to treat multiple CNS disorders and neurodegenerative diseases in addition to MDD, including chronic neuropathic pain, epilepsy, and symptoms of Parkinson's disease and Huntington's disease, where modulation of the NMDAR, AMPA pathway and/or key active metabolites of AV-101 may achieve therapeutic benefit.

Read More

VistaStem Therapeutics is VistaGen's wholly owned subsidiary focused on applying human pluripotent stem cell technology, internally and with collaborators, to discover, rescue, develop and commercialize proprietary new chemical entities (NCEs), including small molecule NCEs with regenerative potential, for CNS and other diseases, and cellular therapies involving stem cell-derived blood, cartilage, heart and liver cells. In December 2016, VistaGen exclusively sublicensed to BlueRock Therapeutics LP, a next generation regenerative medicine company established by Bayer AG and Versant Ventures, rights to certain proprietary technologies relating to the production of cardiac stem cells for the treatment of heart disease.

For more information, please visit http://www.vistagen.com and connect with VistaGen on Twitter, LinkedIn and Facebook.

Forward-Looking Statements

The statements in this press release that are not historical facts may constitute forward-looking statements that are based on current expectations and are subject to risks and uncertainties that could cause actual future results to differ materially from those expressed or implied by such statements. Those risks and uncertainties include, but are not limited to, risks related to the successful launch, continuation and results of the NIMH's Phase 2 (monotherapy) and/or the Company's planned Phase 2 (adjunctive therapy) clinical studies of AV-101 in MDD, and other CNS diseases and disorders, including neuropathic pain and L-DOPA-induced dyskinesia associated with Parkinson's disease, protection of its intellectual property, and the availability of substantial additional capital to support its operations, including the Phase 2 clinical development activities described above. These and other risks and uncertainties are identified and described in more detail in VistaGen's filings with the Securities and Exchange Commission (SEC). These filings are available on the SEC's website at http://www.sec.gov. VistaGen undertakes no obligation to publicly update or revise any forward-looking statements.

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VistaGen Therapeutics Announces Peer-Reviewed Publication in ... - Yahoo Finance

Cardiac Stem Cells Comments Off on VistaGen Therapeutics Announces Peer-Reviewed Publication in … – Yahoo Finance | April 27th, 2017

April 26, 2017 A mouse tibia that has been rendered transparent with Bone CLARITY. Stem cells appear distributed throughout the bone in red. The ability to see bone stem cell behavior is crucial for testing new osteoporosis treatments. Credit: Science Translational Medicine, Greenbaum, Chan, et al; Gradinaru laboratory/Caltech

Ten years ago, the bones currently in your body did not actually exist. Like skin, bone is constantly renewing itself, shedding old tissue and growing it anew from stem cells in the bone marrow. Now, a new technique developed at Caltech can render intact bones transparent, allowing researchers to observe these stem cells within their environment. The method is a breakthrough for testing new drugs to combat diseases like osteoporosis.

The research was done in the laboratory of Viviana Gradinaru (BS '05), assistant professor of biology and biological engineering and a Heritage Medical Research Institute Investigator. It appears in a paper in the April 26 issue of Science Translational Medicine.

In healthy bone, a delicate balance exists between the cells that build bone mass and the cells that break down old bone in a continual remodeling cycle. This process is partially controlled by stem cells in bone marrow, called osteoprogenitors, that develop into osteoblasts or osteocytes, which regulate and maintain the skeleton. To better understand diseases like osteoporosis, which occurs when loss of bone mass leads to a high risk of fractures, it is crucial to study the behavior of stem cells in bone marrow. However, this population is rare and not distributed uniformly throughout the bone.

"Because of the sparsity of the stem cell population in the bone, it is challenging to extrapolate their numbers and positions from just a few slices of bone," says Alon Greenbaum, postdoctoral scholar in biology and biological engineering and co-first author on the paper. "Additionally, slicing into bone causes deterioration and loses the complex and three-dimensional environment of the stem cell inside the bone. So there is a need to see inside intact tissue."

To do this, the team built upon a technique called CLARITY, originally developed for clearing brain tissue during Gradinaru's postgraduate work at Stanford University. CLARITY renders soft tissues, such as brain, transparent by removing opaque molecules called lipids from cells while also providing structural support by an infusion of a clear hydrogel mesh. Gradinaru's group at Caltech later expanded the method to make all of the soft tissue in a mouse's body transparent. The team next set out to develop a way to clear hard tissues, like the bone that makes up our skeleton.

In the work described in the new paper, the team began with bones taken from postmortem transgenic mice. These mice were genetically engineered to have their stem cells fluoresce red so that they could be easily imaged. The team examined the femur and tibia, as well as the bones of the vertebral column; each of the samples was about a few centimeters long. First, the researchers removed calcium from the bones: calcium contributes to opacity, and bone tissue has a much higher amount of calcium than soft tissues. Next, because lipids also provide tissues with structure, the team infused the bone with a hydrogel that locked cellular components like proteins and nucleic acids into place and preserved the architecture of the samples. Finally, a gentle detergent was flowed throughout the bone to wash away the lipids, leaving the bone transparent to the eye. For imaging the cleared bones, the team built a custom light- sheet microscope for fast and high-resolution visualization that would not damage the fluorescent signal. The cleared bones revealed a constellation of red fluorescing stem cells inside.

The group collaborated with researchers at the biotechnology company Amgen to use the method, named Bone CLARITY, to test a new drug developed for treating osteoporosis, which affects millions of Americans per year.

"Our collaborators at Amgen sent us a new therapeutic that increases bone mass," says Ken Chan, graduate student and co-first author of the paper. "However, the effect of these therapeutics on the stem cell population was unclear. We reasoned that they might be increasing the proliferation of stem cells." To test this, the researchers gave one group of mice the treatment and, using Bone CLARITY, compared their vertebral columns with bones from a control group of animals that did not get the drug. "We saw that indeed there was an increase in stem cells with this drug," he says. "Monitoring stem cell responses to these kinds of drugs is crucial because early increases in proliferation are expected while new bone is being built, but long-term proliferation can lead to cancer."

The technique has promising applications for understanding how bones interact with the rest of the body.

"Biologists are beginning to discover that bones are not just structural supports," says Gradinaru, who also serves as the director of the Center for Molecular and Cellular Neuroscience at the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech. "For example, hormones from bone send the brain signals to regulate appetite, and studying the interface between the skull and the brain is a vital part of neuroscience. It is our hope that Bone CLARITY will help break new ground in understanding the inner workings of these important organs."

The paper is titled "Bone CLARITY: Clearing, imaging, and computational analysis of osteoprogenitors within intact bone marrow."

Explore further: Growing new bone for more effective injury repair

More information: Alon Greenbaum et al, Bone CLARITY: Clearing, imaging, and computational analysis of osteoprogenitors within intact bone marrow, Science Translational Medicine (2017). DOI: 10.1126/scitranslmed.aah6518

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Transparent bones enable researchers to observe the stem cells inside - Medical Xpress

Bone Marrow Stem Cells Comments Off on Transparent bones enable researchers to observe the stem cells inside – Medical Xpress | April 27th, 2017

Using video microscopy in the living mouse lung, UC San Francisco scientists have revealed that the lungs play a previously unrecognized role in blood production. As reported online March 22, 2017, inNature, the researchers found that the lungs produced more than half of the platelets blood components required for the clotting that stanches bleeding in the mouse circulation.

In another surprise finding, the scientists also identified a previously unknown pool of blood stem cells capable of restoring blood production when the stem cells of the bone marrow, previously thought to be the principal site of blood production, are depleted.

This finding definitely suggests a more sophisticated view of the lungs that theyre not just for respiration but also a key partner in formation of crucial aspects of the blood, said pulmonologistMark R. Looney, a professor of medicine and of laboratory medicine at UCSF and the new papers senior author. What weve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.

The findings could have majorimplications for understanding human diseases in which patients suffer from low platelet counts, or thrombocytopenia, which afflicts millions of people and increases the risk of dangerous uncontrolled bleeding. The findings also raise questions about how blood stem cells residing in the lungs may affect the recipients of lung transplants.

The new study was made possible by a refinement of a technique known as two-photon intravital imaging recently developed by Looney and co-authorMatthew F. Krummel, a UCSF professor of pathology. This imaging approach allowed the researchers to perform the extremely delicate task of visualizing the behavior of individual cells within the tiny blood vessels of a living mouse lung.

Looney and his team were using this technique to examine interactions between the immune system and circulating platelets in the lungs, using a mouse strain engineered so that platelets emit bright green fluorescence, when they noticed a surprisingly large population of platelet-producing cells called megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up, saidEmma Lefranais, a postdoctoral researcher in Looneys lab and co-first author on the new paper.

More detailed imaging sessions soon revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature, suggesting that more than half of a mouses total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed. Video microscopy experiments also revealed a wide variety of previously overlooked megakaryocyte progenitor cells and blood stem cells sitting quietly outside the lung vasculature estimated at 1 million per mouse lung.

The discovery of megakaryocytes and blood stem cells in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a clever set of lung transplant studies:

First, the team transplanted lungs from normal donor mice into recipient mice with fluorescent megakaryocytes, and found that fluorescent megakaryocytes from the recipient mice soon began turning up in the lung vasculature. This suggested that the platelet-producing megakaryocytes in the lung originate in the bone marrow.

Its fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets, said Guadalupe Ortiz-Muoz, a postdoctoral researcher in the Looney lab and the papers other co-first author. Its possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we dont yet know about.

"Its possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we dont yet know about."

Guadalupe Ortiz-Muoz, postdoctoral researcher in the Mark Looney Lab

In another experiment, the researchers transplanted lungs with fluorescent megakaryocyte progenitor cells into mutant mice with low platelet counts. The transplants produced a large burst of fluorescent platelets that quickly restored normal levels, an effect that persisted over several months of observation much longer than the lifespan of individual megakaryocytes or platelets. To the researchers, this indicated that resident megakaryocyte progenitor cells in the transplanted lungs had become activated by the recipient mouses low platelet counts and had produced healthy new megakaryocyte cells to restore proper platelet production.

Finally, the researchers transplanted healthy lungs in which all cells were fluorescently tagged into mutant mice whose bone marrow lacked normal blood stem cells. Analysis of the bone marrow of recipient mice showed that fluorescent cells originating from the transplanted lungs soon traveled to the damaged bone marrow and contributed to the production not just of platelets, but of a wide variety of blood cells, including immune cells such as neutrophils, B cells and T cells. These experiments suggest that the lungs play host to a wide variety of blood progenitor cells and stem cells capable of restocking damaged bone marrow and restoring production of many components of the blood.

To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia, said Looney, who is also an attending physician on UCSFs pulmonary consult service and intensive care units.

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Looney said. The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation, said pulmonologist Guy A. Zimmerman, who is associate chair of the Department of Internal Medicine at the University of Utah School of Medicine and was an independent reviewer of the new study forNature. The findings have direct clinical relevance and provide a rich group of questions for future studies of platelet genesis and megakaryocyte function in lung inflammation and other inflammatory conditions, bleeding and thrombotic disorders, and transplantation.

The observation that blood stem cells and progenitors seem to travel back and forth freely between the lung and bone marrow lends support to a growing sense among researchers that stem cells may be much more active than previously appreciated, Looney said. Were seeing more and more that the stem cells that produce the blood dont just live in one place but travel around through the blood stream. Perhaps studying abroad in different organs is a normal part of stem cell education.

The study was supported the UCSF Nina Ireland Program in Lung Health, the UCSF Program for Breakthrough Biomedical Research, and the National Heart, Lung, and Blood Institute (NHLBI), a division of the National Institutes of Health (HL092471, HL107386 and HL130324).

It has been known for decades that the lung can be a site of platelet production, but this study amplifies this idea by demonstrating that the murine lung is a major participant in the process, said Traci Mondoro,project officer at the Translational Blood Science and Resources Branch of the NHLBI. Dr. Looney and his team have disrupted some traditional ideas about the pulmonary role in platelet-related hematopoiesis, paving the way for further scientific exploration of this integrated biology.

Additional authors included Axelle Caudrillier,Beat Mallavia,Fengchun Liu, Emily E. Thornton,Mark B. Headley,Tovo David, Shaun R. Coughlin, Andrew D. Leavitt, David M. Sayah, of UCLA; and Emmanuelle Passegu,a former UCSF faculty member who is now director of the Columbia Stem Cell Initiative at Columbia University Medical Center.

Cover photo:iStock/choja

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A local stem cell study is changing the future of orthopedics.

A new study taking place at the Andrews Institute in Northwest Florida could shape the future of orthopedic surgery.

The goal of the study, spearheaded by Dr. Adam Anz and already eight years in the making, is to use stem cells to regrow cartilage.

If approved, it will be the first orthopedics study of its kind done in the United States and only the second in the entire world.

Stem cells are currently utilized most in cancer research and treatments, but Dr. Anz of the Andrews Institute wants to change that by putting regenerative medicine to the test, using stem cells to regrow knee cartilage.

The Andrews Institute already uses stem cells in certain therapies, but this new method could be a game changer.

"The bone marrow aspirate, which we're studying for knee arthritis and we can offer to patients, is the 1990's technology of stem cells," Dr. Anz said. "What we're studying is the modern way to harvest many more stem cells. That's the reason the FDA has said you need to bring this through our process before you just offer it to people."

Through a process called apheresis, stem cells are harvested from the patient with help from a synthetic hormone that promotes the body to generate more stem cells.

"Through this process we can collect millions of cells," Dr. Anz said. "Just 140 milliliters -- about a half of a coke can -- will have 140 million stem cells."

The stem cells will then be sorted, divided and injected into the patient's knee. Excess cells are stored in a nitrogen freezer at negative 181 degrees Celsius until the next round of injections, a process to be repeated over the next two years.

"If this study is successful, this will be the first approved in orthopedics in the United States," said Dr. Anz.

The study begins in May. Dr. Anz believes it will take about another five to seven years before the FDA can approve it for use in patients.

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Two weeks after his transplant, Jonathan Pitre battles kidney complications Ottawa Citizen Pitre, 16, was infused two weeks ago with stem-cell rich blood and bone marrow drawn from his mother's hip. The procedure, conducted as part of an ongoing clinical trial at the University of Minnesota Masonic Children's Hospital, is the only treatment ... and more »

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(EnviroNews World News) Kobe, Japan For more than two million Americans, straight lines may look wavy and the vision in the center of their eye may slowly disappear. Its called age-related macular degeneration (AMD), and there is no cure. But that may change soon.

A surgical team at Kobe City Medical Center General Hospital in Japan recently injected 250,000 retinal pigment epithelial (RPE) cells into the right eye of a man in his 60s. The cells were derived from donor stem cells stored at Kyoto University. It marked the first time that retinal cells derived from a donors skin have been implanted in a patients eye. The skin cells had been reprogrammed into induced pluripotent stem cells (iPS), which can be grown into most cell types in the body.

The procedure is part of a safety study authorized by Japans Ministry of Health that will involve five patients. Each will be followed closely for one year and continue to receive follow-up exams for three additional years. Project leader Dr. Masayo Takahashi at Riken, a research institution that is part of the study, told the Japan Times, A key challenge in this case is to control rejection. We need to carefully continue treatment.

A previous procedure on a different patient in 2014 used stem cells from the individuals own skin. Two years later, the patient reported showing some improvement in eyesight. But the procedure cost $900,000, leading the study team to move forward using donor cells. They expect the costs to come down to less than $200,000.

Among people over 50 in developed countries, AMD is the leading cause of vision loss. According to the National Eye Institute, 14 percent of white Americans age 80 or older will suffer some form of AMD. The condition is almost three times more common among white adults than among people of color. Women of all races comprise 65 percent of AMD cases.

The lack of a cure has led some to try unproven treatments. Three elderly women lost their sight after paying $5,000 each for a stem cell procedure at a private clinic in Florida. Clinic staff used liposuction to remove fat from the womens bellies. They then extracted stem cells from the fat, which were injected into both eyes of each patient in the same procedure, resulting in vision loss in both eyes. Two of the three victims agreed to a lawsuit settlement with the company that owned the clinic.

Stem cell therapy is still at an early stage. As of January 2016, 10 clinical uses have been approved around the world, all using adult stem cells. These include some forms of leukemia and bone marrow disease, Hodgkin and non-Hodgkin lymphoma and some rare inherited disorders including sickle cell anemia. Stem cell transplants are now often used to treat multiple myeloma, which strikes more than 24,000 people a year in the U.S.

Clinical trials to treat type 1 diabetes, Parkinsons disease, stroke, brain tumors and other conditions are being conducted. The first patient in a nationwide clinical study to receive stem cell therapy for heart failure recently underwent the procedure at the University of Wisconsin School of Medicine and Public Health. An experimental treatment at Keck Medical Center of USC last year on a paralyzed patient restored the 21-year-old mans use of his arms and hands. Harvard scientists see stem cell biology as a path to counter aging and extend human lifespans. But the International Society for Stem Cell Research warns that there are many challenges ahead before these treatments are proven safe and effective.

The U.S. Food and Drug Administration (FDA) regulates stem cells to ensure that they are safe and effective for their intended use. But, that doesnt stop some clinics from preying on worried patients. The FDA warns on its website that the hope that patients have for cures not yet available may leave them vulnerable to unscrupulous providers of stem cell treatments that are illegal and potentially harmful.

While there is yet no magic cure for AMD, the Japan study and others may one day lead there. The Harvard Stem Cell Institute (HSCI) in Boston is currently researching retina stem cell transplants. One approach uses gene therapy to generate a molecule that preserves healthy vision. Another involves Muller cells, which give fish the ability to repair an injured retina.

But these therapies are far off. We are at about the halfway mark, but there is still a precipitous path ahead of us, Takahashi said.

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The spinal cord is a rope of nerves relaying messages from the brain to every organ, muscle, and nerve ending in the body. The cells that make up the spinal cord arent a homogeneousmass, but rather a combination of dozens of specialized neurons, each with its own important role to play in guiding signals and impulses to the right destination.

This week, a team of California researchers announced the successful production of a lab-grown neuron that could help heal spinal cord injuries by reestablishing the connection between brain and muscle. In apaperpublished inProceedings of the National Academy of Sciences, researchers from the Gladstone Institutes and University of California campuses in San Francisco and Berkeley described how they grew human spinal cord neurons from stem cells and successfully introduced the lab-grown cells into the spines of healthy mice.

Todd McDevitt is a senior investigator at Gladstone and lead author of the study. He said that his team chose the targeted neuron, called a V2a interneuron, because it serves as a long relay cable between the neurons in the brain and the motor neurons that connect directly to muscle. V2a interneurons are, in fact, some of the longest cells in the body, able to extend their axon the nerve fibers that transmit electrical impulses across several vertebrae.

Its one cell stretching out up to 1,000 times longer than a normal human cell, said McDevitt. These outstretched neurons, as long as several centimeters, seem to play a critical role in relaying messages along the spinal cord. So if they are damaged in a traumatic injury, the brain-muscle connection may be severed, potentially leading to paralysis.

But if those critical V2a interneurons could be regenerated in an injured spine, the researchers wondered, perhaps the spinal cord could re-establish the connection and heal itself.

For the past three years, McDevitt and his team have been working to culture viable human V2a interneurons from pluripotent stem cells. The process, known as differentiation, attempts to replicate in the lab the natural development of neurons from undifferentiated stem cells in a human embryo.

Decades of research in developmental biology have provided clues to how genes in a developing embryo direct different proteins and other chemical factors to create all manner of specialized cells. The trouble is that most of the recipes for these chemical cocktails were derived from studying animal embryos.

Obviously, for good reasons, we dont do experiments on human embryos, McDevitt said. You have to take a leap of faith from the developmental biology knowledge we have from worms and flies and think about how we can apply that really important biological information to the human context.

RELATED:Brain Implant Helps 'Locked-In' ALS Woman Communicate

After experimenting with round after round of chemical combinations, the researchers landed on a process that can now produce a sizable batch of human V2a interneurons in a little over two weeks. The first step was to inject the cells into the spinal cords of healthy mice and see if the cells survived. They did even better.

Within two weeks, we saw a number of these cells extend their axons over long distances five millimeters reliably, but some even longer than that, McDevitt said, adding that the wiry cells are also making important connections. Even though theyre mice, we see these human cells that appear to be connecting to other neurons.

Does this mean were close to a human therapy using injections of healthy neurons to repair damaged spines? Not quite. Trials will first need to be run with injured mice before any human subjects can be tested. Plus, its entirely possible that V2a interneurons only fix very specific types of spinal injuries, or none at all. It might require the production of other spinal cord neurons, or a combination of several, to find the most effective treatment.

At the most basic level, this work shows that we can successfully introduce a new type of spinal neuron made from human pluripotent stem cells, McDevitt said. I see it as a step in whats probably going to be a much bigger effort by the field.

WATCH: Are We Close to Repairing Spinal Cord Injuries?

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Nerve cells derived from human stem cells, in work supported by the California Institute for Regenerative Medicine.

When California voters approved US$3billion in funding for stem-cell research in 2004, biologists flocked to the state, and citizens dreamed of cures for Parkinsons disease and spinal-cord injuries. Now, the pot of money one of the biggest state investments in science is running dry before treatments have emerged, raising questions about whether Californians will pour billions more into stem-cell research.

If they dont, that could leave hundreds of scientists without support, and strand potentially promising therapies before they reach the market. Its an issue of great concern, says Jonathan Thomas, chair of the board for the California Institute for Regenerative Medicine (CIRM) in Oakland.

CIRM is now doling out its final $650million, and its leaders are seeking money from the private sector to carry projects beyond 2020, when the money will run out. Advocates are also surveying voters to determine whether a new request for funding stands a chance in state elections next year. But critics argue against this way of funding research.

California voters saw major opportunities for stem cells in 2004 when they passed Proposition 71, which included an agreement to create the corporation that became CIRM. The move was a reaction to then-US president George W. Bushs decision in 2001 to restrict federal funds for work on human embryonic stem cells.

Since CIRM rolled out its first grants in 2006, it has funded more than 750 projects and reported alluring results from clinical trials. In March, a trial partially funded by CIRM showed that nine out of ten children born with severe combined immunodeficiency or bubble-boy disease a potentially lethal condition in which a persons immune system does not function properly, were doing well up to eight years after treatment (K.L.Shaw etal. J. Clin. Invest. http://doi.org/b6bp; 2017). They no longer need injections to be able to go to school, play outside or survive colds and other inevitable infections.

A dozen facilities constructed by CIRM have helped to push California to the forefront of research on ageing and regenerative medicine. Many grant recipients were early-career academics who had not been able to enter the stem-cell field previously because of the federal restrictions which were loosened in 2009 and the high cost of getting started in this kind of work. That barrier makes it difficult for researchers to gather the preliminary data typically required to win grants from the US National Institutes of Health (NIH).

To milk its remaining $650 million, CIRM partnered last year with the contract-research organization QuintilesIMS in Durham, North Carolina, to carry out clinical trials. CIRM leaders hope that this move will help to guide 40 novel therapies into trials by 2020.

Bob Klein, the property developer who put Proposition 71 on the ballot and established CIRM, isnt waiting for the money to run out. He leads an advocacy group, Americans for Cures, which will soon poll voters to see whether they would approve another $5 billion in funding. If it looks like at least 70% of Californians support that plan, hell start a campaign to put another initiative on the ballot in 2018.

Klein hopes that Californians will rise in support of science at a time when the Trump administration has proposed drastic cuts to the NIH budget. If public enthusiasm is not so strong, Klein says, hell aim for the 2020 elections, when voter turnout should be higher because it will coincide with the next presidential race.

Currently, CIRMs leaders are seeking other sources of support. The majority of our projects will not be ripe for interest from big pharma and the venture-capitalist community by the time we run out of funds, Thomas says. He has been courting large philanthropic foundations and wealthy individuals to raise money to continue the work.

John Simpson, who directs stem-cell oversight work at the advocacy group Consumer Watchdog in Washington DC, plans to oppose any effort to extend CIRM. I acknowledge their scientific advances, but we should not let a flawed process go further, he says. Simpson dislikes the model of using a vote to secure research funding through public bonds, because then the state lacks budgetary control.

Oversight of CIRM has been a problem in the past. In 2012, the US Institute of Medicine found that some scientists vetting grant proposals for CIRM had conflicts of interest. In response, CIRM altered its procedures but the public still felt betrayed. Jim Lott, a member of the state board that oversees CIRMs finances, says that he is not satisfied with the changes. He also argues that CIRM may not have been strategic enough in directing research. Some people say if they had a better focus, they might have achieved cures.

But researchers argue that expectations for cures after only a decade are unrealistic, given the typical pace of drug development. It would be a catastrophe for California if people say CIRM did not do what it was expected to do, says Eric Verdin, president of the Buck Institute for Research on Aging in Novato, California. Theyve built the foundation for the field and attracted people from around the world you cant just now pull the plug.

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A research team at the University of Minnesota found a way to heal broken hearts.

Researchers used a 3D printer to create protein patches that mimic heart tissue to treat post-heart attack scars. The research is in collaboration with the University of Wisconsin-Madison and the University of Alabama-Birmingham.

Brenda Ogle, a University biomedical engineering professor and lead researcher for the project, said she and her team have investigated proteins that surround cells in the body for 15 years. The team has been studying how the proteins also called the extracellular matrix influence stem cell behavior.

For many years, weve been trying to develop optimum formulation that can support stem cells in new cardiac [cell] types, Ogle said, adding that theyve focused on cardiac cell types to figure out a way to strengthen them after the muscle cells are damaged and die during a heart attack. Its one of the cell types in the body that cant be recovered.

The team successfully treated mice with the patches and is now planning to test the method on larger animals.

Molly Kupfer, a doctoral student who is part of Ogles team, said a heart attack occurs when there is a blockage in a primary blood vessel that delivers oxygen and nutrients to the heart.

When that happens, you have cell death in the area of the heart that doesnt receive the appropriate oxygen and nutrients, Kupfer said. Those cells that die arent able to recover."

Typically, after a heart attack, the blood clot in the heart is removed at a hospital, and if the heart has not been damaged too badly, doctors monitor the heart long-term, prescribe medicine and regularly check for signs of heart failure, Ogle said.

What you get instead after a heart attack is scar tissue forming, and that scar tissue ultimately fails, Ogle said.

Associate Professor Brenda Ogle places a 3D printed biopatch on a mouse heart in Nils Hasselmo Hall on Tuesday, April 25, 2017. Her research team induces heart attacks in mice, which causes a dead area of cardiac cells. The patch is placed in this dead zone and mimics the cells of the native heart that aren't able to be replenished on their own.

Kupfer said she worked with Paul Campagnola and his lab at the University of Wisconsin to print the patches; the cells were prepared at the University of Minnesota.

Campagnola, a biomedical engineering professor, said he initially developed the underlying printing technology in 2000.

"The idea of the patch is it could actually behave like native cardiac tissue and assist the function of the heart, Kupfer said, adding that the method used to print the patches results in extremely high resolution structures.

Ogle said before applying the patch to the animal hearts theyre currently testing on, they take a scan of the scarred tissue and create a digital template for the 3D-printer to follow and print the proteins in the same pattern.

Campagnola said the patch provides a stable space for cells to grow and be implanted in damaged areas.

Cardiac cells are also added to the patch when it covers a damaged area. Ogle said it not only provides a support structure, but transplants healthy cells that will eventually become integrated into the heart, stabling it structurally and functionally.

A huge aha moment was when [the cardiac cells] started to beat on this patch synchronously and spontaneously, she said. When that happened, we realized that this could be a viable therapy for the heart, a way to replace those lost muscle cells.

Through the research group at the University of Alabama, Ogle said a study was conducted where the patch was tested on dead or dying tissue in mice hearts and the group saw improvement in the mice after four weeks.

The project was funded through a series of grants from the National Institutes of Health, the National Science Foundation with support from the University, she said.

The group has since received larger funds from the NIH to run a study using the patch on larger animals within the next year.

Ogle said it would take about 10 years until the patch can be used on human patients in a clinical setting.

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UMN research team fixes broken hearts with 3D-printed tissue patch - Minnesota Daily

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It's based on experimental research that suggests stem cells extracted from the pulp of these teeth might someday regrow a lost adult tooth or offer other regenerative medicine benefits -- some potentially life-saving.

"So I'll try not to get emotional here, but my husband was diagnosed with acute myeloid leukemia in 2011," said Bassetto, of Naperville, Illinois, head of a sales team at a software company.

In 2012, her husband, James, had a stem cell transplant to restore his bone marrow and renew his blood.

"He was very fortunate. He was one of six kids, and his brother was a perfect match," she said. She noted that her two children, Madeline, 23, and Alex, 19, may not be so lucky if they develop health problems, since they have only each other; the chance of two siblings being a perfect stem cell match is only 25%.

Unfortunately, her husband's stem cell transplant was not successful. He developed graft-versus-host disease, where his brother's donated stem cells attacked his own cells, and he died shortly afterward.

However, she says, the transplant had given him a chance at a longer life.

Last year, when her son saw a dentist for wisdom tooth pain, a brochure for dental stem cell storage caught Bassetto's eye and struck a chord.

"I know stem cells have tremendous health benefits in fighting disease, and there's a lot ways they're used today," she said. "Had my husband had his own cells, potentially, his treatment could have been more successful."

Medical breakthroughs happen all the time, said Bassetto. "Who knows what potential there is 20 years, 40 years down the road, when my son is an adult or an aging adult?

"Almost like a life insurance policy, is how I viewed it," she said.

Some scientists see storing teeth as a worthwhile investment, but others say it's a dead end.

"Research is still mostly in the experimental (preclinical) phase," said Ben Scheven, senior lecturer in oral cell biology in the school of dentistry at the University of Birmingham. Still, he said, "dental stem cells may provide an advantageous cell therapy for repair and regeneration of tissues," someday becoming the basis for reconstructing bone tissue, retinas and even optic neurons.

Dr. Pamela Robey, chief of the craniofacial and skeletal diseases branch of the National Institute of Dental and Craniofacial Research, acknowledges the "promising" studies, but she has a different take on the importance of the cells.

"There are studies with dental pulp cells being used to treat neurological disorders and problems in the eye and other things," Robey said. The research is based on the idea that these cells "secrete factors that encourage local cells to begin the repair process."

"The problem is, these studies have really not been that rigorous," she said, adding that many have been done only in animals and so provide "slim" evidence of benefits. "The science needs a lot more work."

Robey would know. Her laboratory discovered dental stem cells in 2003.

"My fellows, Songtao Shi and Stan Gronthos, did the work in my lab," Robey said. "Songtao Shi is a dentist, and basically he observed that, when you get a cavity, you get what's called 'reparative dentin.' In other words, the tooth is trying to protect itself from that cavity, so it makes a little bit of dentin to kind of plug the hole, so to speak."

Dentin is the innermost hard layer of tooth that lies beneath the enamel. Underneath the dentin is a soft tissue known as pulp, which contains the nerve tissue and blood supply.

Observing dentin perform reparative work, Shi hypothesized that this must mean there's a stem cell within the tooth that's able to activate and make dentin. So if you wanted to grow an adult tooth instead of getting an implant, knowing how to make dentin would be the start of the process, explained Robey.

Pursuing this idea, Shi, Gronthos and the team conducted their first study with wisdom teeth. They discovered that pulp cells in these third molars did indeed make dentin, but the cells found in baby teeth, called SHED (stem cells from human exfoliated deciduous teeth), had slightly different properties.

"The SHED cells seem to make not only dentin but also something that is similar to bone," Robey said. This "dentin osteogenic material" is a little like bone and a little like dentin -- "unusual stuff," she said.

There is a meticulous process for extracting stem cells from the pulp.

"We very carefully remove any soft tissue that's adhering to the tooth. We treat it with disinfectant, because the mouth is not really that clean," Robey said, laughing.

Scientists then use a dental drill to pass the enamel and dentin -- "kind of like opening up a clam," said Robey -- to get to the pulp. "We take the pulp out, and we digest it with an enzyme to release the cells from the matrix of the pulp, and then we put the cells into culture and grow them."

According to Laning, even very small amounts of dental pulp are capable of producing many hundreds of millions of structural stem cells.

Harvesting dental stem cells is not a matter of waiting for the tooth to fall out and then quickly calling your dentist. When a baby tooth falls out, the viability of the pulp is limited if it's not preserved in the proper solution.

American Academy of Pediatric Dentistry President Dr. Jade Miller explained that "it's critical that the nerve tissue in that pulp tissue, the nerve supply and blood supply, still remain intact and alive." Typically, the best baby teeth to harvest are the upper front six or lower front six -- incisors and cuspids, he said.

For a child between 5 and 8 years of age, it's best to extract the tooth when there's about one-third of the root remaining, Miller said: "It really requires some planning, and so parents need to make this decision early on and be prepared and speak with their pediatric dentist about that."

Bassetto found the process easy. All it involved was a phone call to the company recommended by her dentist.

"They offer a service where they grow the cells and save those and also keep the pulp of the tooth without growing cells from it," she said. "I opted for both." From there, she said, the dentist shipped the extracted teeth overnight in a special package.

Bassetto said she paid less than $2,000 upfront, and now $10 a month for continued storage.

So is banking teeth something parents should be doing?

In a policy statement, the American Academy of Pediatric Dentistry "encourages dentists to follow future evidence-based literature in order to educate parents about the collection, storage, viability, and use of dental stem cells with respect to autologous regenerative therapies."

"Right now, I don't think it is a logical thing to do. That's my personal opinion," said Robey of the National Institute of Dental and Craniofacial Research. As of today, "we don't have methods for creating a viable tooth. I think they're coming down the pike, but it's not around the corner."

Science also does not yet support using dental pulp stem cells for other purposes.

"That's not to say that in the future, somebody could come up with a method that would make them very beneficial," Robey said.

Still, she observed, if science made it possible to grow natural teeth from stem cells and you were in a car accident, for example, and lost your two front teeth, you'd probably be "very happy to give up a third molar to use the cells in the molar to create new teeth." Third molars are fairly expendable, she said.

Plus, Robey explained, it may not be necessary to bank teeth: Another type of stem cell, known as induced pluripotent stem cells, can be programmed into almost any cell type.

"It's quite a different story than banking umbilical cord blood, which we do know contains stem cells that re-create blood," Robey said.

"So cord blood banking -- and now we have a national cord blood bank as opposed to private clinics -- so there's a real rationale for banking cord blood, whereas the rationale for banking baby teeth is far less clear," Robey said.

And there's no guarantee that your long-cryopreserved teeth or cells will be viable in the future. Banking teeth requires proper care and oversight on the part of cryopreservation companies, she said. "I think that that's a big question mark. If you wanted to get your baby teeth back, how would they handle that? How would they take the tooth out of storage and isolate viable cells?"

Provia's Laning, who has "successfully thawed cells that have been frozen for more than 30 years," dismissed such ideas.

"Cryopreservation technology is not the problem here," he said. "Stem cells from bone marrow and other sources have been frozen for future clinical use in transplants for more than 50 years. Similarly, cord blood has a track record of almost 40 years." The technology for long-term cryopreservation has been refined over the years without any substantial changes, he said.

Despite issues and doubts, Miller, of the pediatric dentistry academy, said parents still need to consider banking baby teeth.

A grandparent, he is making the decision for his own family.

"It's really at its infancy, much of this research," he said. "There's a very strong chance there's going to be utilization for these stem cells, and they could be life-saving."

He believes that saving baby teeth could benefit not only his grandchildren but also their older siblings and various other family members if their health goes awry and a stem cell treatment is needed.

"The science is strong enough to show it's not science fiction," Miller said. "There's going to be a significant application, and I want to give my grandkids the opportunity to have those options."

Aside from cost, Miller said there are other considerations: "Is this company going to be around in 30, 40 years?" he asked. "That's not an easy thing to figure out."

Having taken the leap, Bassetto doesn't worry.

"In terms of viability, you know, if something were to happen with the company, you could always get what's stored and move it elsewhere, so I felt I was protected that way," she said. She feels "pretty confident" with her decision and plans to store her grandchildren's baby teeth.

Still, she concedes that her circumstances may be rare.

"Not everybody's going to be touched by some kind of disease where it just hits home," Bassetto said. "For me, that made it a no-brainer."

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Bare bones: Making bones transparent Science Daily Ten years ago, the bones currently in your body did not actually exist. Like skin, bone is constantly renewing itself, shedding old tissue and growing it anew from stem cells in the bone marrow. Now, a new technique developed at Caltech can render ... Scientists turn bones transparent to let them see into marrowSTAT Tissue-Clearing Technique Works on BoneThe Scientist all 4 news articles »

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A bone marrow drive for James Christopher Allums, 21, and his sister Elizabeth, 3, is Monday, May 1 at locations throughout northeast Louisiana.

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The News Star 11:33 a.m. CT April 26, 2017

University of Louisiana Monroe(Photo: Courtesy image)

A bone marrow drive for James Christopher Allums, 21, and his sister Elizabeth, 3, is Monday, May 1 at locations throughout northeast Louisiana.

University of Louisiana Monroe Medical Laboratory Science faculty and students are helping organize the drive. The drive on campus is 9 a.m.-5 p.m. in the SUB and Quad.

May 1 is National Fanconi Anemia Day. James Christopher and Elizabeth suffer from this disease, which is fatal without a bone marrow or stem cell transplant. They are the children of Chris and Ellen Allums.

Melanie Chapman, assistant professor to the School of Health Professions, said, "This is a wonderful opportunity for ULM Warhawks to fly high by working together and setting aside our busy agendas to give two great kids, and possibly others, the chance to live out their years. I am privileged to be a part of ULM and this community effort."

Bone marrow drive locations:

Times vary and new locations may be added. For information, check Facebook The Friends of James Christopher and Elizabeth Allums or visit caringbridge.org and search James Christopher Allums .

MORE NEWS;The Fabulous Equinox Orchestra takes the stage at ULM Friday

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Bone marrow drive for Allums siblings at ULM, other locations - Monroe News Star

Bone Marrow Stem Cells Comments Off on Bone marrow drive for Allums siblings at ULM, other locations – Monroe News Star | April 26th, 2017

This weekend the community will be given the chance to save the life of one of its youngest residents. On Friday, April 28, the AmVets Post No. 94 will host a bone marrow registration drive from 3-7 p.m.

Wade Wachter is the son of Adam and Jenni (Duvall) Wachter of Perryville and the grandson of Terri and Lori Duvall, Robyn Roy, and Rodney and Barb Wachter.

On the outside, little Wade is a normal kid though he has been battling a very rare form of bone marrow failure disorder called Schwachman Diamond Syndrome. This dysfunction of the bone marrow requires a lifesaving transplant. He currently takes medication daily and has routine biopsies to monitor for potential leukemia developments in his body.

This disease is so rare that funding is hard to find, which limits the number of possible treatments available. DKMS is the nonprofit group leading the charge to find a bone marrow match for Wachter.

Recent tests show that Wachter will need an immediate transplant for his best chance to have a normal childhood, and according to the DKMS website only 30 percent of patients find a donor inside their families. Nearly 14,000 patients require donations from matched individuals outside of their family line each year. Out of more than 800,000 donors in the U.S., and over 6 million worldwide, 6 out of 10 patients are still unable to find a compatible donor.

We thank DKMS and our community for working with us to help find Wade a bone marrow match, said Jenni Wachter, Wades mother. From the outside, Wade may look like your average 6-year-old child, when really he has been facing a life-threatening battle for years. Our hope is to grow the bone marrow registry to help increase the chances of finding Wade a match so he can move forward towards a healthy and happy life.

Potential donors include anyone who is in good general health between the ages of 18 to 55. Registration is free and only requires filling out a simple form and a quick swab of the inside of each cheek. DKMS covers the $65 registration and processing fee for each supporter, but donations will be accepted to cover costs.

There are two ways to donate once a match has been found. The first method is the Peripheral Blood Stem Cell (PBSC) donation. This is a non-surgical, outpatient procedure that collects blood stem cells via the bloodstream. It takes about 4-8 hours on 1-2 consecutive days. This method is used in 75 percent of all cases. The other donation method is by direct bone marrow procedure. It is a 1-2 hour surgical procedure, done under anesthesia, where a syringe collects marrow cells from the back of the pelvic bone. This method is only used in about 25 percent of the cases, usually when the patient is a child.

Anyone unable to attend the drive that wishes to register as a potential donor may do so online at http://www.dkms.org. The Perryville AmVets Post No. 94 is located at 1203 W. Saint Joseph Street.

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Bone marrow drive set for local youth - Perry County Republic Monitor

Bone Marrow Stem Cells Comments Off on Bone marrow drive set for local youth – Perry County Republic Monitor | April 26th, 2017

This study aimed to explore the role of the transforming growth factor-/mitogen activated protein kinase (TGF-/MAPK) signaling pathway in the effects of bone marrow mesenchymal stem cells (BMSCs) on urinary control and interstitial cystitis in a rat model of urinary bladder transplantation.

A urinary bladder transplantation model was established using Sprague-Dawley rats. Rats were assigned to normal (blank control), negative control (phosphate-buffered saline injection), BMSCs (BMSC injection), sp600125 (MAPK inhibitor injection), or protamine sulfate (protamine sulfate injection) groups. Immunohistochemistry, urodynamic testing, hematoxylin-eosin staining, Western blotting, enzyme-linked immunosorbent assay, and MTT assay were used to assess BMSC growth, the kinetics of bladder urinary excretion, pathological changes in bladder tissue, bladder tissue ultrastructure, the expression of TGF-/MAPK signaling pathway-related proteins, levels of inflammatory cytokines, and the effects of antiproliferative factor on cell proliferation.

Compared with normal, negative control, BMSCs, and sp600125 groups, rats in the PS group exhibited decreased discharge volume, maximal micturition volume, contraction interval, and bladder capacity but increased residual urine volume, bladder pressure, bladder peak pressure, expression of TGF-/MAPK signaling pathway-related proteins, levels of inflammatory cytokines, and growth inhibition rate. Levels of inflammatory cytokines and the growth inhibition rate were positively correlated with the expression of TGF-/MAPK signaling pathway-related proteins.

Our findings demonstrate that the TGF-/MAPK signaling pathway mediates the beneficial effects of BMSCs on urinary control and interstitial cystitis.

American journal of translational research. 2017 Mar 15*** epublish ***

Ya Xiao, Ya-Jun Song, Bo Song, Chi-Bing Huang, Qing Ling, Xiao Yu

Urological Research Institute of PLA, The First Affiliated Hospital, Third Military Medical UniversityChongqing 400037, P. R. China; Department of Urology, The Second Affiliated Hospital, The Third Military Medical UniversityChongqing 400037, P. R. China., Department of Urology, The Second Affiliated Hospital, The Third Military Medical University Chongqing 400037, P. R. China., Urological Research Institute of PLA, The First Affiliated Hospital, Third Military Medical University Chongqing 400037, P. R. China., Department of Urology, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology Wuhan 430030, P. R. China.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/28386345

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TGF-/MAPK signaling mediates the effects of bone marrow mesenchymal stem cells on urinary control and interstitial ... - UroToday

Bone Marrow Stem Cells Comments Off on TGF-/MAPK signaling mediates the effects of bone marrow mesenchymal stem cells on urinary control and interstitial … – UroToday | April 26th, 2017