Adult Stem Cell Therapies Are Filling the Pipeline

By all measures, we are quickly entering a new era in the treatment of disease and injury: the era of stem cell therapies. Progress in this field was initially slowed because embryonic stem cells raised serious ethical issues and often gave rise to cancer and other side-effects.

But since the discovery of adult stem cells, research has moved forward at an accelerated pace.

By the simplest definition, stem cells are undifferentiated cells that can turn into any number of cell types. There are two sources of adult stem cells:

1. Scientists have developed methods for reprogramming body cells into stem cells that can differentiate, a characteristic known as pluripotency. There are technical hurdles to this approach, but great strides are being made. 2. The discovery of a second source of adult stem cells has generated much excitement for the future of stem cell therapy. These cells can be found naturally among differentiated cells in a tissue or organ, where they are used to repair and maintain that part of the body. Experiments have shown that certain types of these adult stem cells can be coaxed to turn into different cell types. So they could potentially be used to heal tissues that are different than their tissue of origin.

Even a brief review of the many advances in stem cell therapy reveals the tremendous potential this field holds for the future. One study that has gotten a lot of attention recently highlighted a method that may even enable individuals to slow or halt the aging process itself.

The study was done at the University of Pittsburgh School of Medicine by Dr. Johnny Huard, director of the school’s stem cell research center, and Dr. Laura Niedernhofer, a molecular geneticist.1

The researchers were able to regenerate failing organs and dramatically slow the aging process in prematurely aging mice by injecting them with stem cell-like progenitor cells that were taken from the muscles of young, healthy mice.

Life spans of test subjects were doubled and in some cases tripled, while the overall health of the mice was increased. This work is based on three original and major conclusions about aging and potential

interventions to alter the aging process:

? First, adult stem cells deteriorate as a part of aging. The DNA loses much of its ability to repair itself, and the mature cell is less capable of performing its function. This stem cell failure is a signature for aging itself, and the diseases that define and accompany aging, including dementia, osteoporosis, and diabetes. ? Second, using stem cells from younger mice is a way to counter aging. When prematurely aged mice were injected in the abdomen with immature muscle cells from younger healthy mice, they renewed their vigor, they became healthier, and they lived two to three times as long. ? Third, this “fountain of youth” may be found in a secretion from these stem cells. The muscle stem cells released a substance the researchers called “Factor X,” which works its rejuvenating magic all over the mouse’s body.

Today, the research is just beginning. But, within 10 years, Huard hopes to see treatments developed for humans that are based on this research. As he puts it, once “we understand what is being secreted, then maybe we can provide this Factor X . . . in a pill to delay the signs of aging.”

In studies with mice, researchers have successfully reprogrammed adult cells and used them to replace stem cells in the body. If this can be applied to humans, genetic diseases like sickle cell anemia can be cured.

Meanwhile, researchers at UCLA are working on a new way to use stem cells to treat cancer.2 They revealed it is possible to engineer blood stem cells to become cancer-killing T-cells that target human melanoma.

This represents the first time it’s been proven that blood stem cells can be turned into an army of melanoma-fighting T-cells by being genetically altered while still in a living organism.

Dimitrios Vatakis, the study’s lead author, explains the significance of the findings. “These cells can exist in the periphery of the blood, and if they detect the melanoma antigen, they can replicate to fight the cancer.”

In a twist on stem cell therapy, new research from Memorial Sloan-Kettering Cancer Center in New York focuses on combating the stem cells that are thought to cause the recurrence and metastasis of cancer after therapy.3 Their investigation centers on naturally occurring oncolytic viruses that quickly infect and kill cancer stem cells.

It’s believed these viruses can be genetically engineered for use in treating tumors that are particularly resistant to conventional chemotherapy and radiation, such as pancreatic cancer.

Diabetes is another disease being targeted as treatable with stem cell therapy. In Type 1 diabetes, a body’s insulin-producing cells are destroyed by its immune system, rendering the body unable to control blood glucose levels.

In search of a possible therapy, a team at Yale School of Medicine turned to the uterine lining, known as the endometrium, because it is a rich source of adult stem cells.4 The team discovered that bathing these stem cells in cultures containing special nutrients and growth factors created insulin-producing islet cells, like those found in the pancreas.

The objective is to develop islet cells for transplantation that can be used to treat people with Type I diabetes.

Stem cell therapies are also being investigated for their potential to treat injuries.

Experiments carried out at Japan’s Hokkaido University Graduate School of Medicine show promising results for the treatment of brain injuries.5 Stem cells that were injected into the carotid artery traveled directly to the brain in brain-injured rats. Rats that were given the treatment showed significant recovery of motor function. Untreated rats saw no recovery.

When the brains of the treated rats were examined, it was clear the stem cells had transformed into brain cells that contributed to the healing of the injured brain area. This approach shows the promise of treating traumatic brain injury and stroke with stem cell transplantation.

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Bone fractures are another category of injury that may soon be treated through stem cell therapy. For approximately 600,000 people a year, bone fractures do not heal normally.

A team at the University of North Carolina at Chapel Hill, working with mice, found that stem cells that had been enriched with a bone-regenerating hormone helped mend bones that otherwise were not healing within a normal timeframe.6 Their work is the first instance of stem cell therapy that addresses a deficiency in fracture repair, and it may lead to stem cell bone therapies for humans.

Adding to the ongoing effort to find better ways to re-program adult human cells, such as skin cells, to act as stem cells, researchers from the Wellcome Trust Sanger Institute have announced a new technique that increases the efficiency of reprogramming by over 100-fold.

The typical process for reprogramming adult human cells uses four specific regulatory proteins. The Sanger Institute researchers added two additional regulatory factors that dramatically improved efficiency of reprogramming.7 The resulting stem cells were also of a higher quality. For years, mice provided the gold standard in stem cells.

Pentao Liu, from the Sanger Institute, suggests that now, “The reprogrammed cells developed by our team have proved to have the same capabilities as mouse stem cells. Our approach will enable researchers to easily engineer and reprogram human stem cells to generate cell types for cell replacement therapies in humans.”8

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Considering this trend, we offer the following forecasts:

First, as the result of adult stem cell therapies, the cost of treating many ailments will drop substantially over the next 10 to 15 years.

Stem cell therapies will be part of a medical revolution that will provide targeted treatments for diseases. Because stem cell therapies and drugs will increasingly replace expensive surgical solutions, these simplified, yet effective treatments will ultimately be administered by medical technicians rather than more highly-paid physicians, contributing to great cost savings. This pin-point approach will also greatly reduce the cost of dealing with side effects, prolonged hospital stays, and lengthy recovery times.

Second, efficient, specialized facilities will spring up to focus on stem cell therapy.

Today, general hospitals do everything. For that reason, these facilities consist largely of under-utilized capital equipment and highly-paid specialists performing routine procedures that could be performed by nurses or technicians. In the near future, single-purpose medical facilities dedicated to stem cell therapy will maximize the use of their assets, much the way industrial engineering techniques transformed manufacturing and agriculture decades ago.

Third, even as adult stem cell therapies reach commercialization, controversial embryonic stem cell efforts will fall by the wayside.

Geron, formerly the world’s private-sector leader in embryonic stem cell research, recently announced that it was shutting down those efforts.9 Geron’s exit means that Advanced Cell Technology is now the only company that is conducting a clinical trial involving human embryonic stem cells. Meanwhile, numerous clinical trials are underway for a wide range of therapies based on adult stem cell technology.

References List :1. Nature Communications, January 3, 2012, "Muscle-Derived Stem/Progenitor Cell Dysfunction Limits Healthspan and Lifespan in a Murine Progeria Model," by Johnny Huard, Laura J. Niedernhofer, et al. ⓒ Copyright 2012 by Nature Publishing Group, a division of Macmillan Publishers Limited. All rights reserved. http://www.nature.com 2. Proceedings of the National Academy of Sciences, December 20, 2011, Vol. 108, No. 51, "Antitumor Activity from Antigen-Specific CD8 T Cells Generated in Vivo from Genetically Engineered Human Hematopoietic Stem Cells," by Jerome A. Zack, Dimitrios N. Vatakis, et al. ⓒ Copyright 2011 by the National Academy of Sciences. All rights reserved. http://www.pnas.org 3. For more information about using a virus to kill cancer stem cells, visit the Digestive Disease Week website at: http://www.ddw.org 4. Molecular Therapy, November 2011, "Derivation of Insulin Producing Cells from Human Endometrial Stromal Stem Cells and Use in the Treatment of Murine Diabetes," by Hugh S. Taylor, et al. ⓒ Copyright 2011 by the American Society of Gene & Cell Therapy. All rights reserved. http://www.nature.com 5. Neurosurgery, February 2012, "Therapeutic Effects of Intra-Arterial Delivery of Bone Marrow Stromal Cells in Traumatic Brain Injury of Rats ? in Vivo Cell Tracking Study by Near-Infrared Fluorescence Imaging," by Toshiya Osanai, et al. ⓒ Copyright 2012 by the Congress of Neurological Surgeons. All rights reserved. http://journals.lww.com 6. Endeavors, Winter 2009, "Boning Up on Stem Cells," by Susan Hardy. ⓒ Copyright 2009 by the University of North Carolina at Chapel Hill. All rights reserved. http://endeavors.unc.edu 7. For more information about increasing efficiency in reprogramming adult human cells, visit the Wellcome Trust Sanger Institute website at: http://www.sanger.ac.uk 8. Proceedings of the National Academy of Sciences, November 5, 2011, Vol. 108, No. 45, "Rapid and Efficient Reprogramming of Somatic Cells to Induced Pluripotent Stem Cells by Retinoic Acid Receptor Gamma and Liver Receptor Homolog," by Pentao Liu, Wei Wang, et al. ⓒ Copyright 2011 by the National Academy of Sciences. All rights reserved. http://www.pnas.org 9. The New York Times, November 14, 2011, "Geron Is Shutting Down Its Stem Cell Clinical Trial," by Andrew Pollack. ⓒ Copyright 2011 by The New York Times Company. All rights reserved. http://www.nytimes.com