What Lies Behind The Hype And The Hope Of Stem Cell Research And Therapy

The words “stem cell research and therapy” evoke a number of responses. In emotionally vulnerable patients, a sense of hope. In scientists, a great deal of excitement about future prospects. In the case of legal experts and ethicists, a need to ensure that patient safety and a spirit of distributive justice are maintained. And in the minds of entrepreneurs, an opportunity to develop a profitable business.

Stem cells are the building blocks of our bodies. They are able to differentiate into the more that 200 cell types that make up our bodies. From a fertilised egg to a fully-fledged human being which contains billions of cells, the purpose of stem cells during development in the womb is to ensure normal structure and function.

In postnatal life, stem cells replace those cells that have been damaged by wear and tear or by disease.

Gaining Momentum

In research, stem cells are at the cutting edge of science, with regular breakthroughs being announced in the field. By 2012, it was estimated that there were close to 100,000 active stem cell researchers across the globe. Massive funding is being directed globally into research which continues to provide hope to millions of patients.

Stem cell therapy translates the research findings into potential cures for many diseases. For instance, for more than 50 years, bone marrow transplants – also known as hematopoietic stem cell transplants – have been used to treat patients with blood cancers such as leukemia and blood disorders such as sickle cell disease and thalassemia.

When a person with cancer undergoes conditioning chemotherapy to destroy the cancerous cells in the body, in the process this treatment also destroys the patient’s own stem cells. Bone marrow transplants are used to replace these stem cells. This form of treatment is universally employed, and accepted.

More recently, skin grown from stem cells has been used to treat extensive burns and stem cells from fat (adipose tissue) have been used as tissue fillers.

The reality of stem cells versus future promise

Stem cell treatment has saved many lives. But there are also elements of stem cells that have been mired in controversy.

As a result of stem cells becoming a buzzword, there has been a proliferation of websites offering dubious treatments, luring people with incurable diseases who are emotionally vulnerable. There is rarely any form of control over what these clinics place on their websites, let alone the treatments they offer.

Aside from bone marrow transplants and stem cells used for burns, almost all other conditions for which stem cells are advertised to provide a cure are still in an experimental stage. Globally, there are hundreds of legitimate clinical trials underway to assess the effect of stem cells in a variety of conditions including heart disease, spinal cord injury, blindness and Parkinson’s disease, to name a few.

But, in these cases, the road which finally joins the healing properties of stem cells to the approved use of these cells on a routine basis is long and arduous.

Clinical trials need to be undertaken before a treatment can become part of routine medical practice. They must be registered with the relevant national body in the country where they are taking place. Clinical trials also need to be peer reviewed via a registered ethics committee or an institutional review board.

And although rarely mentioned explicitly in legislation or guidelines, patients who receive experimental treatments should not have to pay for these treatments.

Breaching The Law On Multiple Fronts

For most stem cell treatments which have not undergone clinical trials, patients are subjected to therapy which defies the basic ethical and legal principles of the medical profession. Some treatments are blatantly unsafe, such as the infusion of embryonic and animal-derived stem cells into humans.

But practitioners who provide these unproven treatments argue that:

patients are desperate and it is a last resort after trying everything else;

If one uses the patient’s own cells the rules do not apply; and

patients should have the right to decide how they wish to use their cells.

Countries without adequate legislation cannot curb unethical practices and financial exploitation of patients using unproven stem cell treatments. In these countries, unscrupulous medical practitioners providing these therapies often identify the gaps in the law and then head straight for them, using legal tactics and devious interpretations to justify their activities.

Regulating Stem Cell Treatment

To ensure the safety of stem cell treatments and to limit exploitation of vulnerable patients, several measures can be undertaken. These include establishing appropriate legislation, ensuring that this legislation is enforced, and educating the public.

Ethical advertising standards also need to be enforced to limit the dissemination of false information. And patients should feel they have the freedom to approach their medical practitioners for advice on how to proceed.

Without an adequate legislative environment or the enforcement of existing legislation, the medical industry is at risk of facing legal challenges from unsatisfied or damaged patients. This is likely to slow down advances in the field, although it will also provide much needed case law which, due to the relative youth of the field, is still lacking in many countries, including South Africa.

But the outcome could also include a knee-jerk reaction that results in excessively prescriptive legislation that limits research on valuable ethically and scientifically approved projects as well as the translation of research findings into useful products and services.

Source : http://goo.gl/rv7vbI

Newly Discovered Cells Regenerate Liver Tissue Without Forming Tumors

The mechanisms that allow the liver to repair and regenerate itself have long been a matter of debate. Now researchers at University of California, San Diego School of Medicine have discovered a population of liver cells that are better at regenerating liver tissue than ordinary liver cells, or hepatocytes. The study, published August 13 in Cell, is the first to identify these so-called “hybrid hepatocytes,” and show that they are able to regenerate liver tissue without giving rise to cancer. While most of the work described in the study was done in mouse models, the researchers also found similar cells in human livers.

Of all major organs, the liver has the highest capacity to regenerate — that’s why many liver diseases, including cirrhosis and hepatitis, can often be cured by transplanting a piece of liver from a healthy donor. The liver’s regenerative properties were previously credited to a population of adult stem cells known as oval cells. But recent studies concluded that oval cells don’t give rise to hepatocytes; instead, they develop into bile duct cells. These findings prompted researchers to begin looking elsewhere for the source of new hepatocytes in liver regeneration.

In this latest study, led by Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology, researchers traced the cells responsible for replenishing hepatocytes following chronic liver injury induced by exposure to carbon tetrachloride, a common environmental toxin. That’s when they found a unique population of hepatocytes located in one specific area of the liver, called the portal triad. These special hepatocytes, the researchers found, undergo extensive proliferation and replenish liver mass after chronic liver injuries. Since the cells are similar to normal hepatocytes, but express low levels of bile duct cell-specific genes, the researchers called them “hybrid hepatocytes.”

Meanwhile, many other research labs around the world are working on ways to use induced pluripotent stem cells (iPSCs) to repopulate diseased livers and prevent liver failure.

“Although hybrid hepatocytes are not stem cells, thus far they seem to be the most effective in rescuing a diseased liver from complete failure,” said Joan Font-Burgada, PhD, postdoctoral researcher in Karin’s lab and first author of the study.

While iPSCs hold a lot of promise for regenerative medicine, it can be difficult to ensure that they stop proliferating when their therapeutic job is done. As a result, iPSCs carry a high risk of giving rise to tumors. To test the safety of hybrid hepatocytes, Karin’s team examined three different mouse models of liver cancer. They found no signs of hybrid hepatocytes in any of the tumors, leading the researchers to conclude that these cells don’t contribute to liver cancer caused by obesity-induced hepatitis or chemical carcinogens.

“Hybrid hepatocytes represent not only the most effective way to repair a diseased liver, but also the safest way to prevent fatal liver failure by cell transplantation,” Karin said.

Co-authors of this study also include Shabnam Shalapour, Atsushi Umemura, Koji Taniguchi, Mark A. Valasek, Maike Sander, and Hannah Carter, UC San Diego; Suvasini Ramaswamy, and Inder M. Verma, Salk Institute for Biological Studies; Brian Hsueh, Karl Deisseroth, and Li Ye, Howard Hughes Medical Institute and Stanford University; David Rossell, University of Warwick; Hayato Nakagawa, UC San Diego and University of Tokyo; and Janel L. Kopp, UC San Diego and University of British Columbia.

This research was funded by the National Institutes of Health, including the Superfund Research Program at the National Institute of Environmental Health Sciences (grants CA118165, CA155120, P30 CA014195-38, F32CA136124, ES010337, HL053670, AI048034, DK078803 and DK068471), California Institute for Regenerative Medicine, Rotary Foundation, Uehara Memorial Foundation, German Research Foundation, Japan Society for the Promotion of Science, Japanese Society of Gastroenterology, Tokyo Society of Medical Sciences, Kanae Foundation for the Promotion of Medical Science, Frances C. Berger Foundation, Leona M. and Harry B. Helmsley Charitable Trust and JDRF.

Pediatric Neurosurgeon Studies Cord Blood's Role In Repairing Nerve Cells

Dr. James Baumgartner, a pediatric neurosurgeon at Florida Hospital, is trying to see if the stem cells in cord blood can help babies who have a stroke around the time of birth. 

This type of stroke -- called perinatal stroke -- occurs in 1 in 1,000 to 1 in 3,000 babies, according to estimates. These babies usually develop cerebral palsy, have trouble with cognition, walking, bladder function, and many have epilepsy that's difficult to treat.

"What I'm curious about is can the nervous system be repaired or repair itself with cellular therapy," said Baumgartner, surgical director of Comprehensive Epilepsy Center at Florida Hospital for Children. 

The small study is still at very early stages and it's challenging, because not all strokes are the same. The Florida Hospital for Children team is working with Cord Blood Registry to identify willing families whose children have had perinatal stroke. 

If they qualify, the families come to the hospital for an overnight treatment and for several follow-up visits. 

Researchers' goal at this time is to see if cord blood infusion (cellular therapy) is safe, and it helps with the kids' hand movement, improve their bladder function, and reduce the number of their seizures. 

"Also, we're going to use pretty sophisticated neuroimaging to see if we have altered the the trajectory of brain damage, with a simple thought that if you preserve more brain, the patient ought to do better," Baumgartner said. 

Studies suggest that after an injury like stroke, the body's immune system is activated and it may be suppreseeing the nervous system's repair machinery. 

Meanwhile, early research suggests that infusion of cord blood stem cells via a simple IV dials down that immune response, potentially allowing the nerve cells that aren't completely injured to get repaired. 

"I was taught you're born with every nerve cell you'll ever have, and repair is impossible. It's clearly not true. So that's what we're playing around with: the brain repair/regeneration and the interaction of immune system and the nervous system," he said. 

Baumgartner's area of research, which focuses on therapy with human cells instead of using drugs, is a growing area of research. 

In another small study, Baumgartner and colleagues showed that bone marrow stem cells can reduce the intensity of severe trauamatic brain injury in children. 

He's also conducting another study to see if cord blood stem cells can help repair certain kinds of hearing loss in children. That study has not been published yet but "everyone thinks we're moving in a good direction," Baumgartner said. 

source : http://goo.gl/XsR4NK

Source of Liver Stem Cells Identified

Howard Hughes Medical Institute (HHMI) scientists have identified stem cells in the liver that give rise to functional liver cells. The work solves a longstanding mystery about the origin of new cells in the liver, which must constantly be replenished as cells die off, even in a healthy organ.

“We've solved a very old problem,” says Roel Nusse, an HHMI investigator at Stanford University who led the research. “We've shown that like other tissues that need to replace lost cells, the liver has stem cells that both proliferate and give rise to mature cells, even in the absence of injury or disease.” Nusse and his colleagues reported their findings August 5, 2015, in the journal Nature.

The liver is made up mostly of hepatocytes, highly specialized cells that carry out the organ's many tasks, including storing vitamins and minerals, removing toxins, and helping regulate fats and sugars in the bloodstream. As these cells die off, they are replaced by healthy new hepatocytes. The source of those new cells had never been identified, Nusse says.

Stem cells, which replenish their own populations and maintain the ability to develop into more specialized cells, provide new cells in the skin, blood, and other tissues where cells are naturally lost over time. But no stem cells had been found in the liver. Some scientists speculated that mature hepatocytes might maintain their populations by dividing. But Nusse says the mature cells have become so specialized to carry out the work of the liver, they have likely lost the ability to divide.

“Differentiated hepatocytes have amplified their chromosomes,” he explains. That is, the cells have more than the usual two copies of every chromosome. “This enables the cells to make more proteins, but it really compromises their ability to divide.”

Nusse’s lab at Stanford focuses on a family of proteins of called Wnts, which are key regulators of stem cell fate. To find and follow stem cells in a variety of tissues, they have developed mice in which cells that respond to the Wnt signal are labeled with a fluorescent protein. Several years ago, they decided to use the mice to search for stem cells in the liver.

Bruce Wang, a gastroenterologist at the Liver Center at the University of California, San Francisco, led the experiments as a visiting scholar in Nusse’s lab. Wang began by searching for fluorescently labeled, Wnt-responsive cells in the livers of the engineered mice, and he ultimately found them clustered around the liver's central vein.

Once they knew which cells to focus on, the scientists tracked the fluorescently labeled cells’ behavior. Over time, they noticed that the cells they were tracking divided rapidly, steadily replenishing their own population. This was possible because unlike mature hepatocytes, the labeled cells had only two copies of each chromosome. By following the descendents of the stem cells for up to a year, the scientists discovered that these had changed, taking on the specialized features and amplified genomes of mature hepatocytes. “This fits the definition of stem cells,” Nusse says.

As expected, the liver stem cells required Wnt signals to maintain their stem cell identity. Nusse’s team discovered that endothelial cells lining the central vein, the blood vessel around which the stem cells were clustered, released Wnt molecules into the tissue. Stem cells that migrated out of reach of that signal quickly lost their ability to divide into new stem cells and began to develop into mature hepatocytes. Nusse says this is consistent with how stem cells are known to behave in other tissues.

The lab is now investigating how the newly identified stem cells might contribute to regeneration of liver tissue after injury. It will also be important to explore whether liver cancers tend to originate in these replicating cells, as opposed to more mature hepatocytes, Nusse says.