ABC Kellie van Meurs (3rd from R) died of a heart attack last month while receiving stem cell treatment in Moscow.

Rogue operators in Australia and overseas are charging thousands of dollars for ineffectual stem cell treatments, a leading stem cell research group has warned.

And Stem Cells Australia says there is a growing number of patients going overseas for stem cell treatments which are limited in Australia.

A loophole in the therapeutic goods legislation means that doctors are legally allowed to treat patients, both here and overseas, with their own stem cells even if that treatment is unsafe or has not been proven effective through clinical trials.

Stem Cells Australia believes that dozens of doctors in Australia offer the questionable treatments.

"They're selling treatment without any proof of benefit, and without any proof of safety," Associate Professor Megan Munsie, a stem cell biologist at the University of Melbourne, told 7.30.

Annie Leverington was diagnosed with multiple sclerosis in 2007.

She was once a talented flamenco dancer and worked as a court stenographer.

But in 2002 she noticed something was wrong when her fingers started to "drop" during long trials.

Then her feet started to go.

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Rogue stem cell therapy operators charging thousands for ineffective treatments, researchers say

Prof Noel Caplice, director of the Centre for Research in Vascular Biology at University College Cork, displays his stent mesh. Photograph: Michael MacSweeney/Provision

As Prof Noel Caplice describes it, a revolutionary new system that avoids putting patients through heart bypass operations was literally a back-of- the-garage effort.

A cardiologist in Cork, he came up with the treatment when working as a cardiologist at the Mayo Clinic seven years ago. During this time, Caplice and an engineer friend worked on prototype meshes and attaching these to stents.

The treatment introduces cells that encourage the body to make new blood vessels that grow past the blockage, actually reversing the disease in as little as three or four weeks.

The treatment may also offer hope for patients suffering from other cardiovascular disorders such as peripheral artery disease, a common risk in diabetes. And, because it uses the patients own cells, there is no question of rejection, says Caplice, director of University College Corks Centre for Research in Vascular Biology.

This would represent a major step forward in the treatment of coronary artery disease, he adds. Instead of open-heart surgery and stitching in arteries to bypass a blockage, it causes the body to grow its own bypass. He is leading the research, which also involves the Mayo Clinic in the US, and the team has published a paper describing the work in the current issue of the journal Biomaterials.

He came up with the idea when working as a cardiologist at the Mayo Clinic seven years ago, he says.

One area we were interested in was patients who were inoperable, patients who were too ill to face open-heart surgery and who had no options. That represents about 20 to 25 per cent of all patients with coronary artery disease.

He was a scientist physician while at the Mayo as he is now, doing research but also working with patients, and he ran his own laboratory. He originally thought of introducing stem cells to encourage blood vessel growth, but when injected they go everywhere, you cant direct them in the body.

Caplice is also a consultant cardiologist at Cork University Hospital.

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Bypassing surgery for new cardiac treatment

"By directly reprogramming cells we've managed to produce an artificial cell type that, when transplanted, can form a fully organised and functional organ. This is an important first step towards the goal of generating a clinically useful artificial thymus in the lab."

The thymus is the central hub of the immune system sending out infection fighting T-cells.

People with a defective thymus lack functioning T-cells and are highly vulnerable to infections. This is especially hazardous for bone marrow transplant patients, who need a working thymus to rebuild their immune systems after surgery.

Around one in 4,000 babies born each year in the UK have a malfunctioning or completely absent thymus, due to rare conditions such as DiGeorge syndrome.

Thymus disorders can be treated with infusions of extra immune cells or transplantation of a new organ soon after birth. However, such approaches are severely limited by a lack of donors and tissue rejection.

The new research, published in the journal Nature Cell Biology, raises the possibility of creating a whole new functioning thymus using cells manufactured in the laboratory.

While fragments of organs, including hearts, livers and even brains, have been grown from stem cells, no one before has succeeded in producing a fully intact organ from cells created outside the body.

Dr Rob Buckle, head of regenerative medicine at the MRC, said: "Growing 'replacement parts' for damaged tissue could remove the need to transplant whole organs from one person to another, which has many drawbacks not least a critical lack of donors.

"This research is an exciting early step towards that goal, and a convincing demonstration of the potential power of direct reprogramming technology, by which once cell type is converted to another. However, much more work will be needed before this process can be reproduced in the lab environment, and in a safe and tightly controlled way suitable for use in humans."

Chris Mason, Professor of Regenerative Medicine at University College London, said: "Using living cells as therapies has the big advantage in that the functionality of cells is many orders of magnitude greater than that of conventional drugs. Nowhere is this level of functionality more needed than in curing disorders of the immune system.

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British scientists create first complete working organ from cells

British scientists produced a working thymus, a vital immune system "nerve centre" located near the heart.

In future the technique, so far only tested on mice, could be used to provide replacement organs for people with weakened immune systems, scientists believe.

But it might be another 10 years before such a treatment is shown to be effective and safe enough for human patients.

The research by-passed the usual step of generating "blank slate" stem cells from which chosen cell types are derived.

Instead, connective tissue cells from a mouse embryo were converted directly into a completely different cell strain by flipping a genetic "switch" in their DNA.

The resulting thymic epithelial cells (TECs) were mixed with other thymus cell types and transplanted into mice, where they spontaneously organised themselves and grew into a whole structured organ.

Professor Clare Blackburn, from the Medical Research Council (MRC) Centre for Regenerative Medicine at the University of Edinburgh, who led the team of scientists, said: "The ability to grow replacement organs from cells in the lab is one of the 'holy grails' in regenerative medicine. But the size and complexity of lab-grown organs has so far been limited.

"By directly reprogramming cells we've managed to produce an artificial cell type that, when transplanted, can form a fully organised and functional organ. This is an important first step towards the goal of generating a clinically useful artificial thymus in the lab."

If the immune system can be compared with an army, the thymus acts as its operations base. Here, T-cells made in the bone marrow are primed to attack foreign invaders, just as soldiers are armed and briefed before going into battle.

Once deployed by the thymus, the T-cells protect the body by scanning for infectious invaders such as bacteria and viruses, or dangerous malfunctioning cells, for instance from tumours. When an "enemy" is detected, the T-cells mount a co-ordinated immune response that aims to eliminate it.

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First intact organ built from cells created in lab

An Australian-based biomedical company has been given approval from the AFL to use stem-cell therapy on players recovering from injury.

Sydney-based Regeneus has revealed it was recently given permission for its HiQCell treatment on players suffering from such issues as osteoarthritis and tendinopathy.

The treatment is banned by the World Anti-Doping Agency if it is performance-enhancing but allowed if it is solely to treat injuries.

Regeneus commercial development director Steven Barberasaid the regenerative medicine company had sought approval from the AFL for what the company says is "innovative but not experimental" treatment.

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"In 2013, Regeneus sought and received clearance from ASADA [Australian Sports Anti-Doping Authority] for its proprietary HiQCell therapy for use with athletes who participate in sporting competitions subject to the WADA Anti-Doping Code. The AFL is one of many professional sports bodies which applies the WADA Anti-Doping Code within its regulations for players," he said.

"In March this year, the AFL introduced a Prohibited Treatments List as an additional level of scrutiny over and above the WADA code for player treatments. In light of this, Regeneus made a submission to the AFL to confirm that our specific treatment is not prohibited under that list. Subsequently, the chief medical officer of the AFL has recently communicated with our primary Melbourne-based HiQCell medical practitioner that the treatment is not prohibited and can be administered on a case-by-case basis to players.

"We anticipate documented confirmation of this outcome in the near future from the AFL.

"To our knowledge, the permission is specific to HiQCell and not necessarily to cell-based therapies in general."

The AFL confirmed it had given approval on a "case-by-case" basis.

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AFL approves stem-cell treatment

LUMINESCE Stem cell Therapy Dr Nathan Newman
LUMINESCE Stem Cell Technology by JEUNESSE created from Telomere Research. Order Now: http://www.evenyounger.jeunesseglobal.com/PersonalCare.aspx?id=1.

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LUMINESCE Stem cell Therapy Dr Nathan Newman - Video

At the age of 70, many people are retired but Glenn Abbassi is still dashing round the world doing one of the most important jobs ever.

As a volunteer courier for bone marrow register Anthony Nolan, its her mission to travel thousands of miles transporting vital stem cells for seriously ill transplant patients.

So far, during seven years in her role, she has helped to save the lives of 264 people. She has travelled to four continents and more than 30 countries. She even spent last Christmas away from her family in China.

Speaking yesterday in support of a new Anthony Nolan campaign, she said: I wouldnt change it for the world. Every trip I embark on is as important as the next one.

Glenn, a former NHS complaints manager, explained how donated cells have to be with the recipient within 72 hours.

Getting back in time is a matter of life or death, she said.

The cells are used to treat a range of conditions, including cancer and blood disorders.

Glenns role is particularly poignant as her first husband Peter Davies was diagnosed with the blood disorder aplastic anaemia in 1977. He died three years later aged just 43.

She met her current husband Eddie, 68, a retired air conditioning engineer, a few years later when he flew to Britain from his homeland in Iran to donate his bone marrow to his brother.

They fell in love when Eddie lodged with her while his brother recovered.

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Amazing pensioner helps save 264 lives in 30 countries on four continents

Aug. 24, 2014, 2:09 a.m.

An Australian-based biomedical company has been given approval from the AFL to use stem-cell therapy on players recovering from injury.

An Australian-based biomedical company has been given approval from the AFL to use stem-cell therapy on players recovering from injury.

Sydney-based Regeneus has revealed it was recently given permission for its HiQCell treatment on players suffering from such issues as osteoarthritis and tendinopathy.

The treatment is banned by the World Anti-Doping Agency if it is performance-enhancing but allowed if it is solely to treat injuries.

Regeneus commercial development director Steven Barberasaid the regenerative medicine company had sought approval from the AFL for what the company says is "innovative but not experimental" treatment.

"In 2013, Regeneus sought and received clearance from ASADA [Australian Sports Anti-Doping Authority] for its proprietary HiQCell therapy for use with athletes who participate in sporting competitions subject to the WADA Anti-Doping Code. The AFL is one of many professional sports bodies which applies the WADA Anti-Doping Code within its regulations for players," he said.

"In March this year, the AFL introduced a Prohibited Treatments List as an additional level of scrutiny over and above the WADA code for player treatments. In light of this, Regeneus made a submission to the AFL to confirm that our specific treatment is not prohibited under that list. Subsequently, the chief medical officer of the AFL has recently communicated with our primary Melbourne-based HiQCell medical practitioner that the treatment is not prohibited and can be administered on a case-by-case basis to players.

"We anticipate documented confirmation of this outcome in the near future from the AFL.

"To our knowledge, the permission is specific to HiQCell and not necessarily to cell-based therapies in general."

Read more from the original source:
AFL approves stem-cell therapy

Why not embryonic stem cell
Why not embryonic stem cell ? In conversation with Dr Alok Sharma (MS, MCh.) Professor of Neurosurgery Head of Department, LTMG Hospital LTM Medical College, Sion, Mumbai. Stem Cell Therapy...

By: Neurogen Brain and Spine Institute

Here is the original post:
Why not embryonic stem cell - Video

Last week I discussed the current state of stem cell research and the sociopolitical situation surrounding it. As with any controversial or complex subject being shared with the neophyte it is pointless without a physical, material context to put it in. Many people simply don't know something because it doesn't pertain to them. No-one wants to think about disease, let alone talk about it... why in the world would anyone want to research it? I learned very early on in my injury not to hold others accountable for what they do not fully understand. So much of suffering is purely subjective and experiential, how could they possible grasp what I'M feeling? Or vice versa for that matter? That said, ask yourself, why else would I study any kind of infirmity unless I a. had it, or b. was a doctor? This posting will be to inform those of you who do not understand how spinal cord injury happens and the results it can have. It should help you get a stronger grasp on why stem cells are such an interesting possibility.

Spinal cord injury is one of the least understood conditions on the planet. There are approximately 450,000 spinal cord injury survivors in the United States. Compare that to the millions of cancer patients or those with heart disease. It is simply rare. Every spinal cord injury is different, like a finger print. There are thousands of nerves in the spinal cord, one can be damaged or all of them, or none at all. Consider for a moment what the spinal cord is, in the words of Wikipedia...

It gets even more complicated still. There are levels of spinal cord injury. The vertebrae of the spine which becomes injured determines the type or "level" of injury. The cervical spine down to the upper thoracic is classified as Quadriplegia or Tetraplegia the lower you go. Once the injury drops below the third or fourth thoracic vertebrae it becomes Paraplegia.

Clearly we can now see how treating spinal cord injury generally must be done on a case by case basis. When you factor in age, weight, age of injury, lifestyle and amount of therapy it becomes even more complex. Up until now the real treatment has been in progressive physical therapy. The best centers are those who focus solely on rehabilitating injuries to the central nervous system. We can narrow that category down further to those who are committed to continuous movement towards a cure and taking your treatment into your own hands. These facilities are spread throughout the country on such a minimal level many patients devote their entire lives to the cycle of raising money and traveling just for a few days a month, or even a year, to get the level of care they need. Keep in mind the insurance companies will rarely cover even the cost of therapy, let alone travel.

Things are changing however. There is a grassroots movement in medicine that holds exciting promise. I am going to wrap up this portion of the discussion, but next week I'll continue with more on this movement on the horizon, what living with SCI is like and why there is hope in stem cells. Tune in...

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The Stem Cell: Understanding Spinal Cord Injury: Part 1

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Researchers from Rochester, N.Y., and Colorado have revealed that manipulating stem cells prior to transplantation may lead to improved spinal cord repair methods. When nerve fibers are injured in the spinal cord, the severed ends of the nerve fibers fail to regenerate and reconnect with the nervous system circuitry beyond the site of the injury. During early development, the astrocytes cells of the brain and spine are highly supportive of nerve fiber growth, and scientists believe that if properly directed, these cells could play a key role in regenerating damaged nerves in the spinal cord. Rather than transplanting naive stem cells, the team has adopted an approach of pre-differentiating stem cells into better-defined populations of these brain cells. These stem cells are then selected for their ability to promote recovery.

Researchers from Rochester, N.Y., and Colorado have revealed that manipulating stem cells prior to transplantation may lead to improved spinal cord repair methods. When nerve fibers are injured in the spinal cord, the severed ends of the nerve fibers fail to regenerate and reconnect with the nervous system circuitry beyond the site of the injury. During early development, the astrocytes cells of the brain and spine are highly supportive of nerve fiber growth, and scientists believe that if properly directed, these cells could play a key role in regenerating damaged nerves in the spinal cord. Rather than transplanting naive stem cells, the team has adopted an approach of pre-differentiating stem cells into better-defined populations of these brain cells. These stem cells are then selected for their ability to promote recovery.

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Stem Cell Breakthrough in Spinal Cord Injury Repair

Stem Cells and Spinal Cord Injury:

Spinal cord injuries are described at various levels of "incomplete", which can vary from having no effect on the patient to a "complete" injury which means a total loss of function.

Treatment of spinal cord injuries starts with restraining the spine and controlling inflammation to prevent further damage. The actual treatment can vary widely depending on the location and extent of the injury. In many cases, spinal cord injuries require substantial physical therapy and rehabilitation, especially if the patient's injury interferes with activities of daily life.

After a spinal cord injury, many of the nerve fibers at the injury site lose their insulating layer of myelin. As a result, the fibers are no longer able to properly transmit signals between the brain and the spinal cord contributing to paralysis. Unfortunately, the spinal cord lacks the ability to restore these lost myelin-forming cells after trauma.

Tissue engineering in the spinal cord involves the implantation of scaffold material to guide cell placement and foster cell development. These scaffolds can also be used to deliver stem cells at the site of injury and maximize their regenerative potential.

When the spinal cord is damagedeither accidentally (car accidents, falls) or as the result of a disease (multiple sclerosis, infections, tumors, severe forms of spinal bifida, etc.)it can result in the loss of sensation and mobility and even in complete paralysis.

Spinal Cord Injury and Stem Cell Treatment

Adult stem cell transplants for spinal cord injury repair: current state in preclinical research.

Hernndeza J, Torres-Espna A, Navarro X.

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Spinal Cord Injury Stem Cell Treatment - ASCI - Stem Cell ...

Could this experimental treatment reverse damage caused by a heart attack?

The heart muscle relies on a steady flow of oxygen-rich blood to nourish it and keep it pumping. During a heart attack, that blood flow is interrupted by a blockage in an artery. Without blood, the area of heart fed by the affected artery begins to die and scar tissue forms in the area. Over time, this damage can lead to heart failure, especially when one heart attack comes after another.

Though the heart is a tough organ, the damaged portions become unable to pump blood as efficiently as they once could. People who have had a heart attack therefore may face a lifetime of maintenance therapymedications and other treatments aimed at preventing another heart attack and helping the heart work more efficiently.

A new treatment using stem cellswhich have the potential to grow into a variety of heart cell typescould potentially repair and regenerate damaged heart tissue. In a study published last February in The Lancet, researchers treated 17 heart attack patients with an infusion of stem cells taken from their own hearts. A year after the procedure, the amount of scar tissue had shrunk by about 50%.

These results sound dramatic, but are they an indication that we're getting close to perfecting this therapy? "This is a field where, depending on which investigator you ask, you can get incredibly different answers," says Dr. Richard Lee, professor of medicine at Harvard Medical School and a leading expert on stem cell therapy.

"The field is young. Some studies show only modest or no improvement in heart function, but others have shown dramatically improved function," he says. "We're waiting to see if other doctors can also achieve really good results in other patients."

Studies are producing such varied outcomes in part because researchers are taking different approaches to harvesting and using stem cells. Some stem cells are taken from the bone marrow of donors, others from the patient's own heart. It's not clear which approach is the most promising.

Several different types of approaches are being used to repair damaged heart muscle with stem cells. The stem cells, which are often taken from bone marrow, may be inserted into the heart using a catheter. Once in place, stem cells help regenerate damaged heart tissue.

Like any other therapy, injecting stem cells into the heart can fail or cause side effects. If the stem cells are taken from an unrelated donor, the body's immune system may reject them. And if the injected cells can't communicate with the heart's finely tuned electrical system, they may produce dangerous heart rhythms (arrhythmias). So far, side effects haven't been a major issue, though, and that has encouraged investigators to push onward.

Read more:
Repairing the heart with stem cells - Harvard Health ...

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HOWARD, Wis. -- A northeastern Wisconsin girl, who would have died without a bone marrow transplant, has finally met the man whose donation saved her life.

About three years ago, Mira Erdmann was diagnosed with an auto-immune disease that affects about one in a million people. Doctors said a bone marrow transplant was the Howard girl's only chance of survival.

Christian Werth of Germany found out he was Mira's match just three months after he became a donor, WBAY-TV reported.

"That brought me tears. I sat at home. I called my wife. She was at work, and I told her, I said 'It was for a little girl,' " Werth said.

His stem cells were harvested and sent to Mira's doctors in the U.S. Mira received the transplant and pulled through despite several complications and a tentative outcome.

"My part was the smallest one, but it's cool to see that she's now so happy and healthy after all that," Werth said.

The Werths and the Erdmanns initially communicated through letters because registry rules require anonymity for two years.

"When we received letters, there was something blacked out or it was something made to where we couldn't read it," Werth said. "We took a flashlight behind to find some information!"

Werth and his wife flew to Wisconsin to meet with the Erdmanns this week.

"It was almost surreal, because we had been chatting with him on Skype since December, so to see him in person, I thought I would never let him go," Mira's mother, Tania Erdmann, said. "We cried and we hugged, and it was just really emotional."

Original post:
Wisconsin girl meets marrow donor who saved her life

18 hours ago

Anyone who has suffered an injury can probably remember the after-effects, including pain, swelling or redness. These are signs that the body is fighting back against the injury. When tissue in the body is damaged, biological programs are activated to aid in tissue regeneration. An inflammatory response acts as a protective mechanism to enable repair and regeneration, helping the body to heal after injuries such as wounds and burns. However, the same mechanism may interfere with healing in situations in which foreign material is introduced, for example when synthetics are grafted to skin for dermal repair. In such cases, the inflammation may lead to tissue fibrosis, which creates an obstacle to proper physiological function.

The research group of Arun Sharma, PhD has been working on innovative approaches to tissue regeneration in order to improve the lives of patients with urinary bladder dysfunction. Among their breakthroughs was a medical model for regenerating bladders using stem cells harvested from a donor's own bone marrow, reported in the Proceedings of the National Academy of Sciences in 2013.

More recently, the team has developed a system that may protect against the inflammatory reaction that can negatively impact tissue growth, development and function. Self-assembling peptide amphiphiles (PAs) are biocompatible and biodegradable nanomaterials that have demonstrated utility in a wide range of settings and applications. Using an established urinary bladder augmentation model, the Sharma Group treated a highly pro-inflammatory biologic scaffold used in a wide array of settings with anti-inflammatory peptide amphiphiles (AIF-PAs). When compared with control PAs, the treated scaffold showed regenerative capacity while modulating the innate inflammatory response, resulting in superior bladder function.

This work is published in the journal Biomaterials. Says Sharma, "Our findings are very relevant not just for bladder regeneration but for other types of tissue regeneration where foreign materials are utilized for structural support. I also envision the potential utility of these nanomolecules for the treatment of a wide range of dysfunctional inflammatory based conditions."

Explore further: Taking tissue regeneration beyond state-of-the-art

More information: Bury MI, Fuller NJ, Meisner JW, Hofer MD, Webber MJ, Chow LW, Prasad S, Thaker H, Yue X, Menon VS, Diaz EC, Stupp SI, Cheng EY, Sharma AK. The promotion of functional urinary bladder regeneration using anti-inflammatory nanofibers. Biomaterials. Available online 18 August 2014. http://www.sciencedirect.com/science/ ii/S0142961214008667

Journal reference: Proceedings of the National Academy of Sciences Biomaterials

Provided by Children's Memorial Hospital

A new approach to bladder regeneration is capitalizing on the potential of two distinct cell populations harvested from a patient's healthy bone marrow, a new study reports.

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Tissue regeneration using anti-inflammatory nanomolecules

5-4-3-2-1 Product Countdown

Stem Cell Skin Care Reviews presents expert & user reviews and analysis of the best (& worst) products in leading edge anti-aging skin care science. Here are the 5 top ranked products as rated by expert reviewers, who are dermatologists, biologists, estheticians, physicians, and product formulators. Click on a stem cell skin care product name or image to view detailed information, or visitthe all reviewssection to examine a larger selection of stem cell skin care products and to search by name, category, or key word.

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The editors and reviewers here are all science nerds and our passionate pursuit of the best stem cell skin creams on the planet separates us fromneurotypicals andputs us somewhere on the spectrum. That being said, we think this whole subject is critically important to survival of the home sapiens species. Especially to skin care aficionados (many of whom also qualify for nerddom). So our desire here is to find a way to communicate all this arcane knowledge into human-usable information. We might not get it right the first time around, so feel free to ask questions or just say say what??? whenever we obfuscate. We have gathered together a knowledge base which we hope will be helpful.

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Best Stem Cell Skin Care Beauty Creams and Serums

Whats the difference between adult stem cell taken from body fat and from bone marrow
Whats the difference between adult stem cell taken from body fat and from bone marrow? In conversation with Dr Alok Sharma (MS, MCh.) Professor of Neurosurgery Head of Department, LTMG Hospital...

By: Neurogen Brain and Spine Institute

Link:
Whats the difference between adult stem cell taken from body fat and from bone marrow - Video

Abstract

Stem cells represent natural units of embryonic development and tissue regeneration. Embryonic stem (ES) cells, in particular, possess a nearly unlimited self-renewal capacity and developmental potential to differentiate into virtually any cell type of an organism. Mouse ES cells, which are established as permanent cell lines from early embryos, can be regarded as a versatile biological system that has led to major advances in cell and developmental biology. Human ES cell lines, which have recently been derived, may additionally serve as an unlimited source of cells for regenerative medicine. Before therapeutic applications can be realized, important problems must be resolved. Ethical issues surround the derivation of human ES cells from in vitro fertilized blastocysts. Current techniques for directed differentiation into somatic cell populations remain inefficient and yield heterogeneous cell populations. Transplanted ES cell progeny may not function normally in organs, might retain tumorigenic potential, and could be rejected immunologically. The number of human ES cell lines available for research may also be insufficient to adequately determine their therapeutic potential. Recent molecular and cellular advances with mouse ES cells, however, portend the successful use of these cells in therapeutics. This review therefore focuses both on mouse and human ES cells with respect to in vitro propagation and differentiation as well as their use in basic cell and developmental biology and toxicology and presents prospects for human ES cells in tissue regeneration and transplantation.

Several seminal discoveries during the past 25 years can be regarded not only as major breakthroughs for cell and developmental biology, but also as pivotal events that have substantially influenced our view of life: 1) the establishment of embryonic stem (ES) cell lines derived from mouse (108, 221) and human (362) embryos, 2) the creation of genetic mouse models of disease through homologous recombination in ES cells (360), 3) the reprogramming of somatic cells after nuclear transfer into enucleated eggs (392), and 4) the demonstration of germ-line development of ES cells in vitro (136, 164, 365). Because of these breakthroughs, cell therapies based on an unlimited, renewable source of cells have become an attractive concept of regenerative medicine.

Many of these advances are based on developmental studies of mouse embryogenesis. The first entity of life, the fertilized egg, has the ability to generate an entire organism. This capacity, defined as totipotency, is retained by early progeny of the zygote up to the eight-cell stage of the morula. Subsequently, cell differentiation results in the formation of a blastocyst composed of outer trophoblast cells and undifferentiated inner cells, commonly referred to as the inner cell mass (ICM). Cells of the ICM are no longer totipotent but retain the ability to develop into all cell types of the embryo proper (pluripotency; Fig. 1). The embryonic origin of mouse and human ES cells is the major reason that research in this field is a topic of great scientific interest and vigorous public debate, influenced by both ethical and legal positions.

Stem cell hierarchy. Zygote and early cell division stages (blastomeres) to the morula stage are defined as totipotent, because they can generate a complex organism. At the blastocyst stage, only the cells of the inner cell mass (ICM) retain the capacity to build up all three primary germ layers, the endoderm, mesoderm, and ectoderm as well as the primordial germ cells (PGC), the founder cells of male and female gametes. In adult tissues, multipotent stem and progenitor cells exist in tissues and organs to replace lost or injured cells. At present, it is not known to what extent adult stem cells may also develop (transdifferentiate) into cells of other lineages or what factors could enhance their differentiation capability (dashed lines). Embryonic stem (ES) cells, derived from the ICM, have the developmental capacity to differentiate in vitro into cells of all somatic cell lineages as well as into male and female germ cells.

ES cell research dates back to the early 1970s, when embryonic carcinoma (EC) cells, the stem cells of germ line tumors called teratocarcinomas (344), were established as cell lines (135, 173, 180; see Fig. 2). After transplantation to extrauterine sites of appropriate mouse strains, these funny little tumors produced benign teratomas or malignant teratocarcinomas (107, 345). Clonally isolated EC cells retained the capacity for differentiation and could produce derivatives of all three primary germ layers: ectoderm, mesoderm, and endoderm. More importantly, EC cells demonstrated an ability to participate in embryonic development, when introduced into the ICM of early embryos to generate chimeric mice (232). EC cells, however, showed chromosomal aberrations (261), lost their ability to differentiate (29), or differentiated in vitro only under specialized conditions (248) and with chemical inducers (224). Maintenance of the undifferentiated state relied on cultivation with feeder cells (222), and after transfer into early blastocysts, EC cells only sporadically colonized the germ line (232). These data suggested that the EC cells did not retain the pluripotent capacities of early embryonic cells and had undergone cellular changes during the transient tumorigenic state in vivo (for review, see Ref. 7).

Developmental origin of pluripotent embryonic stem cell lines of the mouse. The scheme demonstrates the derivation of embryonic stem cells (ESC), embryonic carcinoma cells (ECC), and embryonic germ cells (EGC) from different embryonic stages of the mouse. ECC are derived from malignant teratocarcinomas that originate from embryos (blastocysts or egg cylinder stages) transplanted to extrauterine sites. EGC are cultured from primordial germ cells (PGC) isolated from the genital ridges between embryonic day 9 to 12.5. Bar = 100 m. [From Boheler et al. (40).]

To avoid potential alterations connected with the growth of teratocarcinomas, a logical step was the direct in vitro culture of embryonic cells of the mouse. In 1981, two groups succeeded in cultivating pluripotent cell lines from mouse blastocysts. Evans and Kaufman employed a feeder layer of mouse embryonic fibroblasts (108), while Martin used EC cell-conditioned medium (221). These cell lines, termed ES cells, originate from the ICM or epiblast and could be maintained in vitro (Fig. 2) without any apparent loss of differentiation potential. The pluripotency of these cells was demonstrated in vivo by the introduction of ES cells into blastocysts. The resulting mouse chimeras demonstrated that ES cells could contribute to all cell lineages including the germ line (46). In vitro, mouse ES cells showed the capacity to reproduce the various somatic cell types (98, 108, 396) and, only recently, were found to develop into cells of the germ line (136, 164, 365). The establishment of human ES cell lines from in vitro fertilized embryos (362) (Fig. 3) and the demonstration of their developmental potential in vitro (322, 362) have evoked widespread discussions concerning future applications of human ES cells in regenerative medicine.

Human pluripotent embryonic stem (ES) and embryonic germ (EG) cells have been derived from in vitro cultured ICM cells of blastocysts (after in vitro fertilization) and from primordial germ cells (PGC) isolated from aborted fetuses, respectively.

Primordial germ (PG) cells, which form normally within the developing genital ridges, represent a third embryonic cell type with pluripotent capabilities. Isolation and cultivation of mouse PG cells on feeder cells led to the establishment of mouse embryonic germ (EG) cell lines (198, 291, 347; Fig. 2). In most respects, these cells are indistinguishable from blastocyst-derived ES cells and are characterized by high proliferative and differentiation capacities in vitro (310), and the presence of stem cell markers typical of other embryonic stem cell lines (see sect. ii). Once transferred into blastocysts, EG cells can contribute to somatic and germ cell lineages in chimeric animals (197, 223, 347); however, EG cells, unlike ES cells, retain the capacity to erase gene imprints. The in vitro culture of PG cells from 5- to 7-wk-old human fetuses led to the establishment of human EG cell lines (326) (Fig. 3). These cell lines showed multilineage development in vitro but have a limited proliferation capacity, and currently can only be propagated as embryoid body (EB) derivatives (325). Following transplantation into an animal model for neurorepair, human EG cell derivatives, however, show some regenerative capacity, suggesting that these cells could be useful therapeutically (190). Although pluripotent EG and EC cells represent important in vitro models for cell and developmental biology, this review focuses mainly on fundamental properties and potential applications of mouse and human ES cells for stem cell research.

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Embryonic Stem Cells: Prospects for Developmental Biology ...

An Australian-based biomedical company has been given approval from the AFL to use stem-cell therapy on players recovering from injury.

Sydney-based Regeneus has revealed it was recently given permission for its HiQCell treatment on players suffering from such issues as osteoarthritis and tendinopathy.

The treatment is banned by the World Anti-Doping Agency if it is performance-enhancing but allowed if it is solely to treat injuries.

Regeneus commercial development director Steven Barberasaid the regenerative medicine company had sought approval from the AFL for what the company says is "innovative but not experimental" treatment.

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"In 2013, Regeneus sought and received clearance from ASADA [Australian Sports Anti-Doping Authority] for its proprietary HiQCell therapy for use with athletes who participate in sporting competitions subject to the WADA Anti-Doping Code. The AFL is one of many professional sports bodies which applies the WADA Anti-Doping Code within its regulations for players," he said.

"In March this year, the AFL introduced a Prohibited Treatments List as an additional level of scrutiny over and above the WADA code for player treatments. In light of this, Regeneus made a submission to the AFL to confirm that our specific treatment is not prohibited under that list. Subsequently, the chief medical officer of the AFL has recently communicated with our primary Melbourne-based HiQCell medical practitioner that the treatment is not prohibited and can be administered on a case-by-case basis to players.

"We anticipate documented confirmation of this outcome in the near future from the AFL.

"To our knowledge, the permission is specific to HiQCell and not necessarily to cell-based therapies in general."

The AFL confirmed it had given approval on a "case-by-case" basis.

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AFL approves stem-cell therapy treatment