Stem Cell Therapy for Spinal Cord Injuries

SCI or Spinal cord injuries usually occur with a sudden & traumatic injury or blow to the spinal cord that dislocates or fractures the vertebrae. The damage of SCI begins at the point of impact when the displaced disc material,bone fragments, or ligaments either bruise or tear the spinal cord tissue. Most SCI injuries do not sever the spinal cord completely. The SCI is likely to cause minor compressions or fractures of the vertebrae, that crush and destroy the signal carriers called axons. Axons carry electric signals up and down our spinal cords and act as a messenger between our brains and the rest of our bodies. SCI generally cause damage to some,many, or in some cases all the axons.

Some SCI victims can accomplish a complete recovery. Others however,will be left with complete paralysis.SCI are classified in two categories, complete or incomplete. A complete SCI is indicated by the total lack of all sensory and motor functions below the area of injury. An incomplete SCI means that the patient has the ability to convey some messages to &/or from the brain but often in a limited capacity. Most People with incomplete SCI injuries can retain minor sensory and/or motor function below the point of injury. Those who survive SCI will most likely suffer for medical complications like bowel and bladder dysfunction and often have chronic pain. Partial SCI patients also have an increased susceptibility to heart & respiratory problems. Successful recovery usingstem cells to treatspinal cord Injuries depends largely on how well systematic failures and chronic conditions are handled day-to-day.

Cell Therapy for injured Spinal Cordsfocuses on regeneration of the connections between your brain and body that have been broken or severely hampered. Stem cellscan help regain motor functions and regain bowel and bladder dysfunction, regain loss of sensations, help minimize chronic pain,cramps and its associated depression. Conventional treatments for SCI today are focused mainly on providing rehabilitation and the prevention of secondary damage. Recent advancements in spinal cord cell treatments offer hope for thousands of victims around the world who are often left with little or no hope for recovery. Stemcell treatments for spinal cord injury can help support and promote the bodies natural regeneration cycle by stimulating the rapid repair of damaged cells and tissue. The regenerative treatmentgoes well beyond the traditional approach of symptomatic treatments and can help you improve and regain some of the previously lost or impaired physical functions. Cell death normally occurs when our cells are injured. These dead cells are surrounded by both damaged and healthy cells. Stem cells stimulate the healing of these injured cells via the secretion of cytokines and other cells such as NGF or nerve growth factors to trigger the body into self-healing mode.

Thai Medical offers a uniquespinal cordtreatment protocol usinga multi-pronged approach. First, adult stem cells are injected directly into the damaged areas of the spine via the accuracy and precision guidance of a CT-guided intra-spinal injection. The treatment is then supplemented even further with another injection using an LP or lumbar puncture and/or IV drip injections.

CT-guided intra-spinal stem cell treatments are considered the gold standard in the field of Stem Cell treatment for spinal cord injury and spinal injury stem cell research for Stem Cell Treatments in Thailand. The precision of CT guidance allows the neurosurgeon to precisely aim the stem cells inside the healthy spinal cord tissues directly adjacent to the injury and lesions. The CT-guided intra-spinal stem cell treatments avoids the requirements of open spine surgeries of yesteryear. CT-guided intra-spinal stem cell treatments also avoid the risks, pain and subsequent healing time associated with cell treatment for SCI (spinal cord injury.)

The objectives of the enrichedcell treatments for spinal cord injuries is to help repair the injured areas on the cellular level near the point of impacts and lesions. The resulting therapy will generally lead to improved quality of life and improved symptoms primarily in physical function,movements and abilities. The majority of patients who are accepted into the program have show dramatic improvements usually after the first or second treatments and continue to improve and regenerate 6 months to a year after treatment. The results are permanent barring new injuries.

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Stem Cell Treatment for Spinal Cord Injuries SCI Therapy

Body clock protects cells from metabolism-generated oxygen radical damage during division

Irvine, Calif., Jan. 6, 2015 -- UC Irvine scientists studying the role of circadian rhythms in skin stem cells found that this clock plays a key role in coordinating daily metabolic cycles and cell division.

Their research, which appears Jan. 6 in Cell Reports, shows for the first time how the body's intrinsic day-night cycles protect and nurture stem cell differentiation. Furthermore, this work offers novel insights into a mechanism whereby an out of synch circadian clock can contribute to accelerated skin aging and cancers.

Bogi Andersen, professor of biological chemistry and medicine, and Enrico Gratton, professor of biomedical engineering, focused their efforts on the epidermis, the outermost protective layer of the skin that is maintained and healed by long-lived stem cells.

While the role of the circadian clock in processes such as sleep, feeding behavior and metabolism linked to feeding and fasting are well known, much less is known about whether the circadian clock also regulates stem cell function.

The researchers used novel two-photon excitation and fluorescence lifetime imaging microscopy in Laboratory of Fluorescence Dynamics in UCI's Department of Biomedical Engineering to make sensitive and quantitative measurements of the metabolic state of single cells within the native microenvironment of living tissue.

They discovered that the circadian clock regulates one form of intermediary metabolism in these stem cells, referred to as oxidative phosphorylation. This type of metabolism creates oxygen radicals that can damage DNA and other components of the cell. In fact, one theory of aging posits that aging is caused by the accumulative damage from metabolism-generated oxygen radicals in stem cells.

The Andersen-Gratton study also revealed that the circadian clock within stem cells shifts the timing of cell division such that the stages of the cell division cycle that are most sensitive to DNA damage are avoided during times of maximum oxidative phosphorylation.

Other studies in animals have linked aging to disruption of circadian rhythms, and Andersen said that accelerated aging could be caused by asynchrony in the metabolism and cell proliferation cycles in stem cells.

"Our studies were conducted in mice, but the greater implication of the work relates to the fact that circadian disruption is very common in modern society, and one consequence of such disruption could be abnormal function of stem cells and accelerated aging," he said.

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Circadian rhythms regulate skin stem cell metabolism and expansion, UCI study finds

In a groundbreaking study that provides scientists with a critical new understanding of stem cell development and its role in disease, UCLA researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research led by Dr. Kathrin Plath, professor of biological chemistry, have established a first-of-its-kind methodology that defines the unique stages by which specialized cells are reprogrammed into stem cells that resemble those found in the embryo.

The study was published online ahead of print in the journal Cell.

Induced pluripotent stem cells (known as iPSCs) are similar to human embryonic stem cells in that both cell types have the unique ability to self-renew and have the flexibility to become any cell in the human body. iPSC cells, however, are generated by reprogramming skin or blood cells and do not require an embryo.

Reprogramming is a long process (about one to two weeks) and largely inefficient, with typically less than one percent of the primary skin or blood cells successfully completing the journey to becoming an iPSC. The exact stages a cell goes through during the reprogramming process are also not well understood. This knowledge is important, as iPSCs hold great promise in the field of regenerative medicine, as they can provide a single source of patient-specific cells to replace those lost to injury or disease. They can also be used to create novel disease models from which new drugs and therapies can be developed.

"This research has broad impact, because by deepening our understanding of cell reprogramming we have the potential to improve disease modeling and the generation of better sources of patient-specific specialized cells suitable for replacement therapy," said Plath. "This can ultimately benefit patients with new and better treatments for a wide range of diseases.

Drs. Vincent Pasque and Jason Tchieu, postdoctoral fellows in the lab of Dr. Plath and co-first authors of the study, developed a roadmap of the reprogramming process using detailed time-course analyses. They induced the reprogramming of skin cells into iPSC, then observed and analyzed on a daily basis or every other day the process of transformation at the single-cell level. The data were collected and recorded over a period of up to two weeks.

Plath's team found that the changes that happen in cells during reprogramming occur in a sequential stage-by-stage manner, and that importantly, the stages were the same across all the different reprogramming systems and different cell types analyzed.

"The exact stage of reprogramming of any cell can now be determined," said Pasque. "This study signals a big change in thinking, because it provides simple and efficient tools for scientists to study stem cell creation in a stage-by-stage manner. Most studies to date ignore the stages of reprogramming, but we can now seek to better understand the entire process on both a macro and micro level."

Plath's team further discovered that the stages of reprogramming to iPSC are different from what was expected. They found that it is not simply the reversed sequence of stages of embryo development. Some steps are reversed in the expected order; others do not actually happen in the exact reverse order and resist a change until late during reprogramming to iPSCs.

"This reflects how cells do not like to change from one specialized cell type to another and resist a change in cell identity," said Pasque. "Resistance to reprogramming also helps to explain why reprogramming takes place only in a very small proportion of the starting cells."

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Pioneering method developed to define stages of stem cell reprogramming

NEW YORK (TheStreet) -- Shares ofNeuralstem (CUR) continue to rise, up 6.25% to $2.89, in morning trading Friday in sympathy with peer company Brainstorm Cell Therapeutics (BCLI) , which touched a one-year high on Friday.

Brainstorm intends to release the final results from its Phase 2a trial of its stem cell therapy NurOwn on Monday. The company describes NurOwn as an "autologous, adult stem cell therapy technology" designed to treat ALS, also known as Lou Gehrig's Disease.

The company will host a conference call on Monday to discuss the results.

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Neuralstem (CUR) Stock Rises Today as Brainstorm Cell Therapeutics Soars

Cancers due to bad luck, left, and cancers due to a combination of bad luck, environmental factors, and inherited factors. Elizabeth Cook]

Cancers due to bad luck, left, and cancers due to a combination of bad luck, environmental factors, and inherited factors. / Elizabeth Cook]

Nearly two-thirds of all cancers are caused by random mutations of the body's stem cells, not by hereditary or environmental effects, according to a study released Jan. 1 by Johns Hopkins scientists.

Tissues with the most divisions of regenerative cells and hence the most chances for mutations tend to have the greatest rates of cancer, the study found.

This explains why skin cancers, for example, are far more common than bone cancers. Skin cells die constantly, so they must be replenished far more often than those that make bone, introducing more chances for errors that lead to cancer.

In effect, most cancers come down to "bad luck", the researchers say in the study.

The findings introduce new dimensions to the struggle against cancer, said two researchers who did not take part in the study.

The study was published Thursday in the journal Science. Cristian Tomasetti of the Johns Hopkins Kimmel Cancer Center at Johns Hopkins Medicine in Baltimore is first author. The study's senior author is Bert Vogelstein, also of the center, part of Johns Hopkins University.

Healthy diet and protection against carcinogens are still important, said Tomasetti, because the one-third variability is still substantial. And the proportion of randomness in each type of cancer varies. Some cancers tend to be greatly increased by environmental factors, such as lung cancer in smokers. The two-third average is a summary of the risk of cancer from all tissue types.

Strong relationship

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Most cancer is bad luck, study finds

IMAGE:Induced pluripotent stem cells (iPSCs) derived from patients with frontotemporal dementia were genetically corrected and converted to cortical neurons. The green staining indicates the cortical marker CTIP2, the red stain... view more

Credit: Susanna Raitano/Stem Cell Reports 2014

Belgian researchers have identified a new strategy for treating an inherited form of dementia after attempting to turn stem cells derived from patients into the neurons most affected by the disease. In patient-derived stem cells carrying a mutation predisposing them to frontotemporal dementia, which accounts for about half of dementia cases before the age of 60, the scientists found a targetable defect that prevents normal neurodevelopment. These stem cells partially return to normal when the defect is corrected.

The study appears in the December 31st issue of Stem Cell Reports, the official journal of the International Society of Stem Cell Research published by Cell Press.

"Use of induced pluripotent stem cell (iPSC) technology"--which involves taking skin cells from patients and reprogramming them into embryonic-like stem cells capable of turning into other specific cell types relevant for studying a particular disease--"makes it possible to model dementias that affect people later in life," says senior study author Catherine Verfaillie of KU Leuven.

Frontotemporal disorders are the result of damage to neurons in parts of the brain called the frontal and temporal lobes, gradually leading to behavioral symptoms or language and emotional disorders. Mutations in a gene called progranulin (GRN) are commonly associated with frontotemporal dementia, but GRN mutations in mice do not mimic all the features of the human disorder, which has limited progress in the development of effective treatments.

"iPSC models can now be used to better understand dementia, and in particular frontotemporal dementia, and might lead to the development of drugs that can curtail or slow down the degeneration of cortical neurons," Verfaillie says.

Verfaillie and Philip Van Damme of the Leuven Research Institute for Neuroscience and Disease explore this approach in the Stem Cell Reports study by creating iPSCs from three patients carrying a GRN mutation. These immature cells were impaired at turning into mature, specialized cells called cortical neurons--the most affected cell type in frontotemporal dementia.

One of the top defective pathways in the iPSCs was the Wnt signaling pathway, which plays an important role in neuronal development. However, genetic correction or treatment with a compound that inhibits the Wnt signaling pathway restored the ability of the iPSCs to turn into cortical neurons. Taken together, the findings demonstrate that the GRN mutation causes the defect in cortical neuron formation by altering the Wnt signaling pathway.

"Our findings suggest that signaling events required for neurodevelopment may also play major roles in neurodegeneration," Van Damme says. "Targeting such pathways, as for instance the Wnt pathway presented in this study, may result in the creation of novel therapeutic approaches for frontotemporal dementia."

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Patient stem cells used to make dementia-in-a-dish; help identify new treatment strategy

NIH-funded study yields encouraging early results

Three-year outcomes from an ongoing clinical trial suggest that high-dose immunosuppressive therapy followed by transplantation of a person's own blood-forming stem cells may induce sustained remission in some people with relapsing-remitting multiple sclerosis (RRMS). RRMS is the most common form of MS, a progressive autoimmune disease in which the immune system attacks the brain and spinal cord. The trial is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and conducted by the NIAID-funded Immune Tolerance Network (ITN) .

Three years after the treatment, called high-dose immunosuppressive therapy and autologous hematopoietic cell transplant or HDIT/HCT, nearly 80 percent of trial participants had survived without experiencing an increase in disability, a relapse of MS symptoms or new brain lesions. Investigators observed few serious early complications or unexpected side effects, although many participants experienced expected side effects of high-dose immunosuppression, including infections and gastrointestinal problems. The three-year findings are published in the Dec. 29, 2014, online issue of JAMA Neurology.

These promising results support the need for future studies to further evaluate the benefits and risks of HDIT/HCT and directly compare this treatment strategy to current MS therapies, said NIAID Director Anthony S. Fauci, M.D. If the findings from this study are confirmed, HDIT/HCT may become a potential therapeutic option for people with this often-debilitating disease, particularly those who have not been helped by standard treatments.

Scientists estimate that MS affects more than 2.3 million people worldwide. Symptoms can vary widely and may include disturbances in speech, vision and movement. Most people with MS are diagnosed with RRMS, which is characterized by periods of relapse or flare up of symptoms followed by periods of recovery or remission. Over years, the disease can worsen and shift to a more progressive form.

In the study, researchers tested the effectiveness of HDIT/HCT in 25 volunteers with RRMS who had relapsed and experienced worsened neurological disability while taking standard medications. Doctors collected blood-forming stem cells from participants and then gave them high-dose chemotherapy to destroy their immune systems. The doctors returned the stem cells to the participants to rebuild and reset their immune systems.

Notably, participants did not receive any MS drugs after transplant, yet most remained in remission after three years, said Daniel Rotrosen, M.D., director of NIAIDs Division of Allergy, Immunology and Transplantation. In contrast, other studies have shown that the best alternative MS treatments induce much shorter remissions and require long-term use of immunosuppressive drugs that can cause serious side effects.

The study researchers plan to follow participants for a total of five years, recording all side effects associated with the treatment. Final results from this and similar studies promise to help inform the design of larger trials to further evaluate HDIT/HCT in people with MS.

The work was sponsored by NIAID, NIH, and conducted by the ITN (contract number N01 AI015416) and NIAID-funded statistical and clinical coordinating centers (contract numbers HHSN272200800029C and HHSN272200900057C). The ClinicalTrials.gov identifier for the study High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is NCT00288626.

NIAID conducts and supports research at NIH, throughout the United States, and worldwide to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

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News & Events

Abstract: Adipose tissue is an abundant source of mesenchymal stem cells, which have shown promise in the field of regenerative medicine. Furthermore, these cells can be readily harvested in large numbers with low donor-site morbidity. During the past decade, numerous studies have provided preclinical data on the safety and efficacy of adipose-derived stem cells, supporting the use of these cells in future clinical applications. Various clinical trials have shown the regenerative capability of adipose-derived stem cells in subspecialties of medical fields such as plastic surgery, orthopedic surgery, oral and maxillofacial surgery, and cardiac surgery. In addition, a great deal of knowledge concerning the harvesting, characterization, and culture of adipose-derived stem cells has been reported. This review will summarize data from in vitro studies, pre-clinical animal models, and recent clinical trials concerning the use of adipose-derived stem cells in regenerative medicine.

Introduction

In the field of regenerative medicine, basic research and preclinical studies have been conducted to overcome clinical shortcomings with the use of mesenchymal stem cells (MSCs). MSCs are present in adult tissues, including bone marrow and adipose tissue. For many years, bone marrow-derived stem cells (BSCs) were the primary source of stem cells for tissue engineering applications (Caplan, 1991; Pittenger et al., 1999; Caplan, 2007). However, recent studies have shown that subcutaneous adipose tissue provides a clear advantage over other stem cell sources due to the ease with which adipose tissue can be accessed as well as the ease of isolating stem cells from harvested tissue (Schffler et al., 2007). Initial enzymatic digestion of adipose tissue yields a mixture of stromal and vascular cells referred to as the stromal-vascular fraction (SVF) (Traktuev et al., 2008). A putative stem cell population within this SVF was first identified by Zuk et al. and named processed lipoaspirate (PLA) cells (Zuk et al., 2001; Zuk et al., 2002).

There is no consensus when it comes to the nomenclature used to describe progenitor cells from adipose tissue-derived stroma, which can sometimes lead to confusion. The term PLA refers to adipose-derived stromal cells and adipose-derived stem cells (ASCs) and describes cells obtained immediately after collagenase digestion. Accordingly, the term ASC will be used throughout this review.

ASCs exhibit stable growth and proliferation kinetics and can differentiate toward osteogenic, chondrogenic, adipogenic, myogenic, or neurogenic lineages in vitro (Zuk et al., 2002; Izadpanah et al., 2006; Romanov et al., 2005). Furthermore, a group has recently described the isolation and culture of ASCs with multipotent differentiation capacity at the single-cell level (Rodriguez, et al., 2005).

Using these attractive cell populations, recent studies have explored the safety and efficacy of implanted/administrated ASCs in various animal models. Furthermore, clinical trials using ASCs have been initiated in some medical subspecialties. This review summarizes the current preclinical data and ongoing clinical trials and their outcomes in a variety of medical fields.

Characterization and Localization

ASCs express the mesenchymal stem cell markers CD10, CD13, CD29, CD34, CD44, CD54, CD71, CD90, CD105, CD106, CD117, and STRO-1. They are negative for the hematopoietic lineage markers CD45, CD14, CD16, CD56, CD61, CD62E, CD104, and CD106 and for the endothelial cell (EC) markers CD31, CD144, and von Willebrand factor (Zuk et al., 2002; Musina et al., 2005; Romanov et al., 2005). Morphologically, they are fibroblast-like and preserve their shape after expansion in vitro (Zuk et al., 2002; Arrigoni et al., 2009; Zannettino et al., 2008).

The similarities between ASCs and BSCs may indicate that ASCs are derived from circulating BSCs, which infiltrate into the adipose compartment through vessel walls (Zuk et al., 2002; Zannettino et al., 2008; Brighton et al., 1992; Canfield et al., 2000; Bianco et al., 2001). On the other hand, according to a recent theory, these stem cells are actually pericytes (Traktuev et al., 2008; Chen et al., 2009; Crisan et al., 2008; Zannettino et al., 2008; Tintut et al., 2003; Abedin et al., 2004; Amos et al., 2008). Pericytes around microvessels express alpha-smooth muscle actin (-SMA) as well as certain MSC markers (CD44, CD73, CD90, CD105); however, they do not express endothelial or hematopoietic cell markers (Chen et al., 2009). Pericytes adhere, proliferate in culture, sustain their initial antigenic profile, and can differentiate into bone, cartilage and fat cells (Chen et al., 2009). Moreover, injected MSCs migrate to the blood vessels in vivo and become pericytes (Chen et al., 2009). Considering the above-mentioned data, it can be speculated that pericytes are the ancestors of MSCs, but this does not mean that all MSCs are descendants of pericytes (Chen et al., 2009) or that all pericytes are necessarily stem cells (Lin et al., 2008; Traktuev et al., 2008; da Silva et al., 2008; Abedin et al., 2004; Tintut et al., 2003; Zannettino et al., 2008; Amos et al., 2008).

Traktuev et al. (2008) defined a periendothelial pericyte-like subpopulation of ASCs. These cells were CD34+, CD31-, CD45-, and CD144- and expressed mesenchymal cell markers, smooth muscle antigens, and pericytic markers, including chondroitin sulfate proteoglycan (NG2), CD140a, and CD140b (PDGF receptor and , respectively) (Traktuev et al., 2008; Amos et al., 2008). However, Lin et al. (2008) could not co-localize CD34 and CD104b, and thus concluded that CD34+/CD31- cells of adipose vasculature are not pericytes.

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Adipose-derived Stem Cells: Current Findings and Future ...

Experimental treatment kills off, then 'resets' the immune system

WebMD News from HealthDay

By Dennis Thompson

HealthDay Reporter

MONDAY, Dec. 29, 2014 (HealthDay News) -- An experimental therapy that kills off and then "resets" the immune system has given three years of remission to a small group of multiple sclerosis patients, researchers say.

About eight in 10 patients given this treatment had no new adverse events after three years. And nine in 10 experienced no progression or relapse in their MS, said lead author Dr. Richard Nash of the Colorado Blood Cancer Institute at Presbyterian/St. Luke's Medical Center in Denver.

"I think we all think of this as a viable therapy," Nash said. "We still need to perform a randomized clinical trial, but we're all pretty impressed so far, in terms of what we've seen."

In multiple sclerosis, the body's immune system for some unknown reason attacks the nervous system, in particular targeting the insulating sheath that covers the nerve fibers, according to the U.S. National Institutes of Health. People with the more common form, called relapsing-remitting MS, have attacks of worsening neurologic function followed by partial or complete recovery periods (remissions).

Over time, as the damage mounts, patients become physically weak, have problems with coordination and balance, and suffer from thinking and memory problems.

This new therapy seeks to reset the immune system by killing it off using high-dose chemotherapy, then restarting it using the patient's own blood stem cells. Doctors harvest and preserve the patient's stem cells before treatment, and re-implant them following chemotherapy.

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Stem Cell Therapy for MS Shows Promise

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun. Reminding broken hearts how to mend them selves. After years of tracking down the right genetic buttons a team at the Salk Institute in La Jolla has taught a mammal to do what zebra fish do naturally, repair a severely damaged heart. While all our cells have the genetic code for building whole organs those genes seem to be switched off in all higher animals, but active in some more primitive species like zebra fish and salamanders.

New cells (red) repairing injury in a zebra fish heart.

When, with CIRM funding, they inserted genetic signals to turn off those genes in the mice, they saw significant repair of the damaged heart. There are many steps between this advance and getting human hearts to repair them selvesnotably finding a way to introduce the genetic signals without using the virus used in this study. HealthCanal picked up the institutes press release.

Cloned stem cells pretty much like reprogrammed stem cells. In the early days of stem cell research there was a great deal of excitement about the possibility of creating stem cells that genetically match a patient by a process commonly called cloning. This process of taking the genetic storehouse of a cell, the nucleus, and inserting it into a donor egg had been relatively easy in mice. But it turned out quite difficult in humans and was only accomplished last year.

During the years of failed attempts at this process known as nuclear transfer in humans an alternative came into the field. The Nobel prize-winning discovery that you can reprogram any adult cell to act like an embryonic stem cell gave us a new way to create personalized stem cells that genetically match a patient. But ever since that 2008 advance, the research community has fretted over whether those new stem cells called iPS cells really match embryonic stem cells. The iPS cells came from older cells that had lived through many opportunities for mutation and the genetic factors used to reprogram them added further opportunities for mutation.

Researchers at the New York Stem Cell Foundations in house lab have now compared the two types of cells with several layers of genetic analysis. They found the same level of mutation in the iPS cells and the cells from nuclear transfer lending some reassurance to the use of iPS cells going forward. HealthCanal ran the foundations press release.

A more efficient way to make cloned stem cells. Even though a team in Oregon overcame the obstacles to creating stem cells by nuclear transfer last year, and the feat has been repeated by the New York team above and others, it remains terribly inefficient. So, several groups are working on better ways to make these potentially valuable cells.

A former colleague now at Childrens Hospital, Boston wrote a nice explanation of how researchers are going about making these cloned cells easier in the hospitals blog, Vector. Stem cells reduced seizures. The seizures endured by people with many forms of epilepsy originate from genetic defects in their nerves. So, a team at McClean Hospital outside of Boston implanted healthy nerves grown from embryonic stem cells in mice with genetically linked seizures. Half the mice no longer had seizures and the other half had their seizure frequency reduced.

The type of nerves transplanted are called interneurons, which are known to be the nerves that reduce firing of signals. In epilepsy nerve signals are hyperactive. The team is now working on methods to mature the stem cells into purer populations of just the desired interneurons. ClinicalSpace picked up the hospitals press release.

Don Gibbons

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Stem cell stories that caught our eye: heart repair ...

CORDLIFE is now the largest network of private cord blood banks in Asia Pacific with state-of-the-art cord-blood and tissue processing and cryopreservation facilities in the country.

Once considered a medical waste, the blood left in the umbilical cordthe part of the placenta that delivers nutrients to a fetusafter a baby is delivery is now known to be a rich source of blood-forming stem cells.

These cells have been found to be potentially useful in treating diseases that require stem cell transplants (also called bone marrow transplants) such as certain kinds of leukemia or lymphoma, aplastic anemia (a blood disorder in which the bodys bone marrow doesnt make enough new blood cells), severe sickle cell disease and severe combined immunodeficiency.

Unlike with bone marrow, which is obtained through a painful medical procedure, there is only one chance to collect this seemingly precious stuff: immediately after the babys birth.

This is why a number of expectant parents in the country are being offered a chance to save stem cells from their babys umbilical cord blood via what is known as cord-blood banking.

Safeguard

Cordlife Philippines medical director Arvin Faundo said: Its a type of safeguard because the genetically unique stem cells have current and potential uses in medical treatment. No parent wishes his/her child to experience the heartbreaking effects of any illness. What we at Cordlife offer them is the chance to prepare for potential eventualitiesto secure the future well-being and happiness of their family.

Cordlife Philippines is a subsidiary of Cordlife Group Ltd., a company listed on the Singapore Exchange. Launched in February 2010 as the Philippines first and only cord-blood processing and cryopreservation facility, its facility was ISO-certified and built in accordance to global gold standards such as the American Association of Blood Banks.

The 365-day facility, located within UP-Ayala Land TechnoHub in Quezon City, is equipped with the worlds most advanced fully automated cord-blood processing system, the Swiss-made Sepax.

CordLife uses the US FDA-approved cryogenic storage pouch.

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Freezing newborns own stem cells for possible future use

Researchers have cracked the code of how hair growth is activated Key was cells usually used to fight invading pathogens in the body

By Mark Prigg for MailOnline

Published: 18:41 EST, 24 December 2014 | Updated: 19:19 EST, 24 December 2014

Researchers claim to have cracked the code of how hair growth is activated.

They say the discovery could have implications for baldness treatments in humans.

Researchers were able to pinpoint the signals from the skin cells that activate hair growth.

The discovery could have implications for baldness treatments in humans, as researchers were able to pinpoint the signals from the skin cells that activate hair growth.

Macrophages are cells from the immune system that are in charge of devouring invading pathogens, a process called phagocytosis.

The authors report that macrophages induce hair growth by surrounding and activating cells in the skin that have regenerative capacity, called stem cells.

The discovery that macrophages activate skin stem cells could influence technologies with potential applications in tissue regeneration, aging, and cancer.

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Baldness breakthrough: Researchers find skin signals that spark hair growth

Henderson, NV (PRWEB) December 23, 2014

After a successful educational outreach trip to Florida the weekend before Thanksgiving, Hylunia's Head of Research and Development Dr. Link will visit Arizona from Dec. 11-13 giving talks to students and industry professionals.

Dr. Link will be at the Southwest Institute of Natural Aesthetics in Tempe, Arizona this Thursday and Friday. On Saturday, skin care industry professionals are invited to sit in on his third lecture.

This series of lectures follows his successful talk to 60 students at the Florida College of Natural Health in Fort Lauderdale, FL.

The best way to give back to our partners is to host seminars and get them familiar with our ingredients," said Dr. Link. "Its a great way to tell them the reasons behind why were updating formulas and using the ingredients weve chosen so that our partners can tell their customers about why the ingredients are important to their skin care needs.

The lectures explore the benefits, ingredients, philosophy and technology behind Hylunia products. For example, the Dr. Link discusses the science behind cutting-edge ingredients like tomato and grape stem cells, which are major components of Hylunia's Ultimate Antioxidant Cream.

Plant stem cells currently feature in six Hylunia products, including the Ultimate Antioxidant Cream. Tomato and grape stem cells are the newest addition to its lineup, with others on the way.

Grape stem cells protect the skin from free radicals caused by the sun and other environmental stressors like pollution and food. They're also shown to prevent skin aging. Tomato stem cells contain compounds like Lypocene, which protect against the heavy metals found in pollution and other environmental stressors. Dr. Link's lectures aim to explain these benefits to the company's partners who then communicate them to the public.

Hylunia launched its own spa earlier this year, and Dr. Link decided it was the right time to go back on the road and continue his educational outreach to students and industry professionals across the country.

"These speeches give us a chance to spread our philosophy to those who arent familiar with Hylunia," said said Dr. Link.

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Hylunia Head of Research and Development Gives Traveling Lectures on Plant Stem Cells

How does CDI's technology work? A human biological sample, for example blood or skin, is obtained, and the cells within the sample are grown under appropriate cell culture conditions. In the episomal reprogramming method, vectors containing multiple reprogramming genes are introduced into the cells.

While the vectors turn genes in the cell on and off, reprogramming them to a stem cell state, they do not integrate into the genome itself. This method alleviates concerns arising over the potential risks associated with the insertion of foreign DNA to induce reprogramming, which other prior iPS methods use (bottom row in illustration above).

iPS cells are somatic cells (e.g., skin or blood) that have been genetically reprogrammed to a pluripotent stem cell state through forced expression of pluripotency genes.By definition, iPS cells replicate indefinitely and have the potential to differentiate into any cell type in the human body.

Reprogramming factors are the genes introduced into somatic cells that induce a pluripotent stem cell state. Initial reports describing the creation of human iPS cells utilized four reprogramming factors: OCT4, SOX2, KLF4 and MYC (OSKM) (Takahashi, et al. 2007) or OCT4, SOX2, NANOG and LIN28 (OSNL) (Yu, et al. 2007). Subsequent studies revealed that reprogramming using a specific combination of all 6 of these factors combined with SV40LT and a cocktail of small molecules yields iPS cells at much higher efficiency (Yu, et al. 2009; Yu, et al. 2011).

iPS cells are genetically reprogrammed through forced expression of pluripotency genes into somatic cells.The expression of these genes can be accomplished using a variety of different methods.The episomal reprogramming method introduces pluripotency genes into a target cell using circular DNA plasmid vectors (i.e. episomes) that replicate autonomously within the cell cytoplasm and do not integrate into the host cell genome.

Initial methods of iPS cell reprogramming utilized retroviral and lentiviral vectors to introduce pluripotency genes into somatic cells. While these methods generally work well, the viral DNA integrates into the genome of the target cell, and the resulting iPS cells (and cells differentiated from them) will contain foreign DNA, which may result in defects and errors. By contrast, episomal vectors replicate autonomously within the cell cytoplasm and do not integrate into the host genome. In addition, the episomal vectors are released from the target cell at a rate of ~5% per cell cycle resulting in transgene-free or footprint-free iPS cells.These features, combined with recent advancements in episomal reprogramming efficiency, have led to a strong preference for this method to alleviate concerns about genome integrity for drug discovery and cell therapy applications.

Episomal reprogramming has been reported successful from a variety of somatic cells, including fibroblasts, lymphoblastoid cells, and peripheral blood mononuclear cells. Importantly, CDI has optimized its episomal reprogramming method to achieve high efficiency iPS cell generation from small amounts of human peripheral blood. Not only does this enable more streamlined and less invasive collection of donor samples, but ensures increased sterility and lower cost production of iPS cells. In addition, efficient iPS cell production from peripheral blood enables access to large banks of normal and disease-associated clinical samples for disease research and drug screening.

CDIs suite of MyCell Products includes episomal reprogramming of customer-provided donor samples and subsequent genetic engineering and/or differentiation of the iPS cells. In addition, for researchers who would like to generate their own iPS cells, CDIs episomal reprogramming technology is available as a kit from Life Technologies, including Episomal iPSC Reprogramming Vectors, Vitronectin, and Essential 8 Medium. Customer-generated iPS cells using this kit may then be transferred to CDI for genetic engineering and/or differentiation through MyCell Products.

Integration-free iPS cells have been generated using a variety of methods including adenovirus, Sendai virus, piggyBac, minicircle vectors, and direct introduction of protein or synthesized mRNA. The efficiency and success rate of these methods varies depending on the source of somatic cells and experimental conditions, but in general these approaches are limited by impractically low reprogramming efficiency, requirement for higher biosafety containment, and/or labor- and cost-intensive protocols that require repeated transfection/infection.Compared to these methods, episomal reprogramming is virus-free, safe to use, stable, and inexpensive.

A variety of small molecules have been identified that can functionally substitute for one or more reprogramming factors and/or improve the efficiency of iPS cell reprogramming. However, no combination of small molecules has been shown to functionally substitute for all four reprogramming factors. The use of small molecules in iPS cell reprogramming offers some practical advantages including the ability to optimize the chemical structure, fine-tune dose and concentration, and simplify handling and application protocols. However, the use of small molecules presents a number of scientific challenges. Most notably, small molecules may have more than one target, which may or may not be known. In addition, unexpected toxicity and other side effects in vivo may interfere with the clinical application of small molecules.

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CDI | iPS Cells - Cellular Dynamics International

Two men in landmark heart stem cell study tell their stories.

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Jim Dearing of Louisville, Ky., one of the first men in the world to receive heart stem cells, might have helped start a medical revolution that could lead to a cure for heart failure.

Three years after getting the experimental stem cell procedure, following two heart attacks and heart failure, Dearings heart is working normally.

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The difference is clear and dramatic -- and it's lasting, according to findings now being made public for the first time.

Dearing first showed "completely normal heart function" on an echocardiogram done in 2011, says Roberto Bolli, MD, who is leading the stem cell trial at the University of Louisville. Those results have not been published before.

That was still true in July 2012, when Dearing again showed normal heart function on another echocardiogram.

Based on those tests, Bolli says, "Anyone who looks at his heart now would not imagine that this patient was in heart failure, that he had a heart attack, that he was in the hospital, that he had surgery, and everything else."

It's not just Dearing who has benefited. His friend, Mike Jones, who had even more severe heart damage, also got the stem cell procedure in 2009. Since then, scarred regions of his heart have shrunk. His heart now appears leaner and stronger than it was before.

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Stem Cell Research: Heart Stem Cells May Help Heal Hearts ...

Consider the relationship between an air traffic controller and a pilot. The pilot gets the passengers to their destination, but the air traffic controller decides when the plane can take off and when it must wait. The same relationship plays out at the cellular level in animals, including humans. A region of an animal's genome -- the controller -- directs when a particular gene -- the pilot -- can perform its prescribed function.

A new study by cell and systems biologists at the University of Toronto (U of T) investigating stem cells in mice shows, for the first time, an instance of such a relationship between the Sox2 gene which is critical for early development, and a region elsewhere on the genome that effectively regulates its activity. The discovery could mean a significant advance in the emerging field of human regenerative medicine, as the Sox2 gene is essential for maintaining embryonic stem cells that can develop into any cell type of a mature animal.

"We studied how the Sox2 gene is turned on in mice, and found the region of the genome that is needed to turn the gene on in embryonic stem cells," said Professor Jennifer Mitchell of U of T's Department of Cell and Systems Biology, lead invesigator of a study published in the December 15 issue of Genes & Development.

"Like the gene itself, this region of the genome enables these stem cells to maintain their ability to become any type of cell, a property known as pluripotency. We named the region of the genome that we discovered the Sox2 control region, or SCR," said Mitchell.

Since the sequencing of the human genome was completed in 2003, researchers have been trying to figure out which parts of the genome made some people more likely to develop certain diseases. They have found that the answers are more often in the regions of the human genome that turn genes on and off.

"If we want to understand how genes are turned on and off, we need to know where the sequences that perform this function are located in the genome," said Mitchell. "The parts of the human genome linked to complex diseases such as heart disease, cancer and neurological disorders can often be far away from the genes they regulate, so it can be dificult to figure out which gene is being affected and ultimately causing the disease."

It was previously thought that regions much closer to the Sox2 gene were the ones that turned it on in embryonic stem cells. Mitchell and her colleagues eliminated this possibility when they deleted these nearby regions in the genome of mice and found there was no impact on the gene's ability to be turned on in embryonic stem cells.

"We then focused on the region we've since named the SCR as my work had shown that it can contact the Sox2 gene from its location 100,000 base pairs away," said study lead author Harry Zhou, a former graduate student in Mitchell's lab, now a student at U of T's Faculty of Medicine. "To contact the gene, the DNA makes a loop that brings the SCR close to the gene itself only in embryonic stem cells. Once we had a good idea that this region could be acting on the Sox2 gene, we removed the region from the genome and monitored the effect on Sox2."

The researchers discovered that this region is required to both turn Sox2 on, and for the embryonic stem cells to maintain their characteristic appearance and ability to differentiate into all the cell types of the adult organism.

"Just as deletion of the Sox2 gene causes the very early embryo to die, it is likely that an abnormality in the regulatory region would also cause early embryonic death before any of the organs have even formed," said Mitchell. "It is possible that the formation of the loop needed to make contact with the Sox2 gene is an important final step in the process by which researchers practicing regenerative medicine can generate pluripotent cells from adult cells."

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Cell biologists discover on-off switch for key stem cell gene

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Newswise An innovative targeted payload immunotherapy that is being readied for a Phase 3 clinical trial (due to begin in the first half of 2015), received a favorable endorsement from Actinium Pharmaceuticals Scientific Advisory Board (SAB). The nod occurred after the members conducted its year-end meeting to review the progress of Iomab-B, a radiolabeled antibody being developed as a part of bone marrow transplant regimen initially in relapsed and refractory AML patients ages 55 and older.

The group met prior to the 56th American Society of Hematology (ASH) Annual Meeting and Exposition in San Francisco and was Chaired by John Pagel, MD PhD of the Fred Hutchinson Cancer Research Center and Swedish Cancer Institute in Seattle and included senior members from Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center and other leading institutions. The SABs goal is to further the development of Iomab-B as a myeloablative agent for older relapsed and refractory AML patients. If approved, Iomab-B should increase the number of patients eligible for curative bone marrow transplant (BMT, also known as HSCT) and improve clinical outcomes.

Richard Champlin MD, Chair of Stem Cell Transplantation and Cellular Therapy at MD Anderson Cancer Center, stated, We are impressed with progress in Iomab-B development and are looking forward to starting the trial. Iomab-B treatment would be an important new addition to our unfortunately very limited armamentarium for the most difficult-to-treat AML patients, and could potentially change the way refractory AML in older patients is treated.

As an international leader in the field of hematopoietic stem cell transplantation (HSCT), Dr. Champlin pioneered the use of donor transplants and lower doses of chemotherapy, reducing mortality rates along the way. Under his leadership, the MD Anderson HSCT program grew to become the largest in the world.

The Company updated the SAB on progress made in 2014, including refining and completing the Phase 3 protocol, progress in manufacturing centralization and scale-up, CRO engagement and the completion of other administrative items. Plans for 2015 were also reviewed, including assembly of the IND (Investigational New Drug) Application for submission to FDA early next year, clinical trial sites selection, preparation of ancillary materials and other items related to the upcoming pivotal trial. This study is planned as the final clinical trial prior to potential FDA clearance and approval.

Dr. Dragan Cicic, Chief Medical Officer of Actinium stated: "Actinium is committed to the ongoing development of Iomab-B with a multi-center Phase 3 pivotal trial due to begin in 2015. With the continued support and input from our world renowned scientific advisors, we are moving quickly to advance Iomab-B development. The SAB meeting further supported our belief that, if approved by FDA, Iomab-B could significantly change the treatment paradigm for elderly relapsed and refractory AML patients by providing a potentially curative pathway for majority of patients who today have a life expectancy of 5 or fewer months."

About AML Acute myeloid leukemia (AML) is an aggressive cancer of the blood and bone marrow. It is characterized by an uncontrolled proliferation of immature blast cells in the bone marrow. The American Cancer Society estimates there will be approximately 18,860 new cases of AML and approximately 10,460 deaths from AML in the U.S. in 2014, most of them in adults. Patients over age 60 comprise the majority of those diagnosed with AML, with a median age of a patient diagnosed with AML being 67 years. Treatment approaches in this population are limited because a majority of these individuals are judged too frail and unable to tolerate standard induction chemotherapy or having forms of disease generally unresponsive to currently available drugs. Elderly, high risk patients ordinarily have a life expectancy of 5 or fewer months if treated with standard chemotherapy, and only about a third of them receive this treatment because of toxicity of and limited responses to the available therapy. The other two-thirds receive best supportive care, with 2 months survival, according to Oran and Weisdorf (Haematologica 2012; 1916-24).

About Iomab-B Iomab-B will be used in preparing patients for hematopoietic stem cell transplantation (HSCT), the fastest growing hospital procedure in the U.S. The Company established an agreement with the FDA that the path to a Biologics License Application (BLA) submission could include a single, pivotal Phase 3 clinical study if it is successful. The trial population in this two arm, randomized, controlled, multicenter trial will be refractory and relapsed Acute Myeloid Leukemia (AML) patients over the age of 55. The trial size was set at 150 patients with 75 patients per arm. The primary endpoint in the pivotal Phase 3 trial is durable complete remission, defined as a complete remission lasting at least 6 months and the secondary endpoint will be overall survival at one year. There are currently no effective treatments approved by the FDA for AML in this patient population and there is no defined standard of care. Iomab-B has completed several physician sponsored clinical trials examining its potential as a conditioning regimen prior to HSCT in various blood cancers including the Phase 1/2 study in relapsed and/or refractory AML patients. The results of these studies in over 300 patients have demonstrated the potential of Iomab-B to create a new treatment paradigm for bone marrow transplants by: expanding the pool to ineligible patients who do not have any viable treatment options currently; enabling a shorter and safer preparatory interval for HSCT; reducing post-transplant complications; and showing a clear survival benefit including curative potential.

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Experts in Leukemia and Bone Marrow Transplant Prepare for Upcoming Pivotal Trial of Innovative Targeted Payload ...

Seattle After tackling the brain, the Ebola epidemic, and a host of other issues, billionaire Paul Allen has a new target for scientific philanthropy: unraveling the inner workings of human cells.

On Monday, the Microsoft co-founder announced a $100 million, five-year grant to establish the Allen Institute for Cell Science in Seattle.

The goal is to better understand the teeming world inside cells, where thousands of organelles and millions of molecules interact in a dynamic ballet that researchers are just beginning to fathom.

We really dont have a good idea of how normal cells work, and what goes wrong in disease, said Rick Horwitz, the former University of Virginia professor who jumped at the chance to lead the new institute. People spend careers trying to understand little parts of the cell, but nobody has stitched it together because its too complicated for any individual to study.

The institute will take on the challenge by combining new technologies, like microscopes that can visualize living cells in three dimensions, with enough computational firepower to make sense of the flood of data that will result, Horwitz said.

Eventually, he and his team hope to develop computer models that mimic living cells. If they succeed, those models could also shed light on what goes haywire in cancer and other diseases and help develop cures, he said.

At a time when federal research budgets are shrinking, the announcement is one of the most exciting things to happen in Seattle science in a long time, said Dr. Chuck Murry, co-director of the Institute for Stem Cell and Regenerative Medicine at the University of Washington. When the Allen folks get into something, they do it at a scale thats just mind-blowing.

The grant is one of Allens largest, on par with the $100 million he committed earlier this year to fight Ebola in West Africa, and a $100 million grant in 2003 to establish the Seattle-based Allen Institute for Brain Science. He has since plowed an additional $300 million into the brain institute.

Allen, who joined his old partner Bill Gates in pledging to donate the bulk of his wealth, has stepped up his philanthropic efforts in recent years. Its a good bet he will continue investing in the cell institute as long as it measures up, said Allan Jones, who leads the Allen Institute for Brain Science and helped organize its new sister institute.

We need to knuckle down and show that we can deliver something very powerful, Jones said.

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Microsoft Co-Founder Establishes Cell Institute with $100 Million Grant

Irvine, California (PRWEB) December 08, 2014

The Ageless Derma skin care company has added a moisturizing product to their line that provides continuous hydration to skin throughout the day. The Swiss Apple Stem Cell Oil-Free Continuous Moisturizer uses rare Swiss apple stem cells in combination with other natural substances to aid in skins retention of moisture for a lessening of fine lines and a silky, more comfortable feeling.

The Swiss Apple Stem Cell Oil-Free Continuous Moisturizer contains stem cells from the exotic Malus Domestica, a rare apple from Switzerland known for its long shelf life and its ability to stay fresh without shriveling. This apple species had a flavor that consumers found too acidic, making farmers reluctant to grow it. The Malus Domestica, however, was discovered to have interesting scientific advantages due to its ability to live a long, healthy life without the usual shriveling that accompanies fruit as it ages. The same idea has been transferred to Ageless Dermas latest moisturizer with its incorporation of these stem cell extracts for a renewed and rejuvenated facial complexion. The stem cells help with not only apple longevity, but also with repairing human skin cells. This results in the ultimate reduction of fine lines and wrinkles with regular use.

Other ingredients are added to the Swiss Apple Stem Cell Oil-Free Continuous Moisturizer to make this moisturizer a workhorse of anti-aging and hydrating skin renewal. Ceramides and essential fatty acids account for maximum skin hydration and strengthening of the skin barrier function. Capric Triglycerides silken skin, glycerin keeps moisturization and hydration in balance, and Ceramides 3, 611, and 1 (all lipids) stop moisture from escaping and hold the skin barrier intact. Swiss Apple Stem Cell Oil-Free Continuous Moisturizer also has sodium hyaluronate to attract and keep moisture in. The hyaluronate also aids in blood microcirculation and the smoothing of wrinkles.

The developers at Ageless Derma Skin Care know they are making something extraordinary happen. Their line of physician-grade skin care products incorporates an important philosophy: supporting overall skin health by delivering the most cutting-edge biotechnology and pure, natural ingredients to all of the skin's layers. This attitude continues to resonate to this day with the companys founder, Dr. Farid Mostamand, who nearly ten years ago began his journey to deliver the best skin care alternatives for people who want to have healthy and beautiful looking skin at any age. About this latest Ageless Derma product, Dr. Mostamand says, The Swiss Apple Stem Cell Oil-Free Continuous Moisturizer is a multi-beneficial product that protects skin and works to smooth lines and wrinkles as it keeps moisture in, working throughout the entire day. Without the correct distribution of moisture, skin becomes dry and susceptible to wrinkling. This product is oil-free and can be used for any skin type.

Ageless Derma products are formulated in FDA-approved Labs. All ingredients are inspired by nature and enhanced by science. Ageless Derma products do not contain parabens or any other harsh additives, and they are never tested on animals. The company has developed five unique lines of products to address any skin type or condition.

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Ageless Derma Launches Its Latest Moisturizing Product Featuring Exotic Apple Stem Cells

A team of scientists that included researchers from UCLA has discovered a novel mechanism of RNA regulation in embryonic stem cells. The findings are strong evidence that a specific chemical modification, or "tag," on RNA plays a key role in determining the ability of embryonic stem cells to adopt different cellular identities.

The team also included scientists from Harvard Medical School, Massachusetts General Hospital and Stanford University.

Published in the journal Cell Stem Cell, the research reveals that depleting or knocking out a key component of the machinery that places this chemical tag -- known both as m6A and N6-methyladenosine -- on RNA significantly blocks embryonic stem cells from differentiating into more specialized types of cells.

A key property of embryonic stem cells is their ability to differentiate into many specialized types of cells. However, instead of marching toward a specific fate when prompted by signals to differentiate, embryonic stem cells that have reduced ability to place m6A become stuck in a sort of suspended animation, even though they appear healthy.

Yi Xing, a UCLA associate professor of microbiology, immunology and molecular genetics, led the informatics analyses and was a co-corresponding author of the paper. Other corresponding authors were Dr. Cosmas Giallourakis, an assistant professor of medicine at Harvard Medical School and Massachusetts General Hospital, and Dr. Howard Chang, a professor of Stanford University's School of Medicine and a Howard Hughes Medical Institute investigator.

The study of naturally occurring chemical modifications on RNAs is part of an emerging field known as epitranscriptomics. The m6A tag is the most commonly occurring modification known to scientists; it is found on RNAs of thousands of protein-coding genes and hundreds of non-coding genes in a typical cell type. The tags may help regulate RNA metabolism by marking them for destruction.

Little was known about the dynamics, conservation and function of m6A in human or mouse embryonic stem cells when the authors began the project. The authors analyzed which RNAs were tagged with m6A and the location of the m6A modifications along RNAs in mouse and human embryonic stem cells.

"Our analysis revealed a high level of conservation of m6A patterns between mice and humans, suggesting that m6A has conserved functions in human and mouse embryonic stem cells," Xing said. "Moreover, RNAs with m6A tags were degraded more rapidly and lived a shorter life in the cell than those without."

The investigators then found a strikingly conserved requirement for the presence of normal levels of m6A for differentiating embryonic stem cells into multiple cell types. Depletion of METTL3, a gene encoding the enzyme that places the m6A tag on RNAs, severely blocked human embryonic stem cells from differentiating into the gut or neural precursors. Deletion of the mouse METTL3 gene also led to a severe block in the ability of embryonic stem cells to differentiate into neural and cardiac lineages.

The study suggests that m6A modifications on RNA make the transition between cell states possible by instructing the cells to physically degrade those RNAs marked by m6A in embryonic stem cells, to allow the cells to become another cell type. However, if the cells can no longer tag RNA for destruction, the cells lose the ability to change. This discovery sheds new light on gene regulation in stem cells.

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Loss of a chemical tag on RNA keeps embryonic stem cells in suspended animation