ROAD TO THE CURE UPDATE FEBRUARY 2017

By:Ram S. Bhatt, PhD, CEO & CSO PROS AND CONS OF STEM CELL THERAPY PROS AND CONS OF STEM CELL THERAPY Back in 2007 (10 years ago) Jim Fossett, of AMBI/Rockefeller Institute, Federalism and Bioethics Initiative, compiled data on the amount of money being spent on Stem Cell research: Allocations, via NIH, have been roughly flat at $640 million annually for the last couple of years; California, on its own, has already obligated more than $200 million; The California Institute of Regenerative Medicine (CIRM), the state agency which manages the stem cell program, is spending more than five times what NIH is spending (or roughly $3.2 Billion); States could be spending over $500 million annually on stem cell research over the next 8 to10 years; and, Foundations and private philanthropists are spending a ton of money on HESC (Human Embryonic Stem Cell).

While we don’t have it all by a long shot, we have counted some $1.7 billion in private donations. The question might be: What is there to show after spending billions on stem cell research? Stem cells have not been shown to halt the progression of Parkinson’s or Alzheimer’s disease. There have been some reports of symptomatic relief in a handful of patients. What Are Stem Cells? Stem cells are mother cells with the potential to become any type of cell in the body. One of the main properties of stem cells is their ability to self-renew or multiply while maintaining the potential to develop into other types of cells. Stem cells can become cells of the heart, muscles, bones, skin, brain, blood, etc. There are different sources of stem cells but all types of stem cells have the same capacity to self-renew (make copies of themselves). Types of Stem Cells. There are several types of stem cells: i.  Embryonic Stem Cells (ESCs) ii. Tissue-Specific Stem Cells iii. Mesenchymal Stem Cells iv. Induced Pluripotent Stem Cells (IPSCs) In this article we will mainly focus on ESCs and IPSCs. i. Embryonic Stem Cells Embryonic stem cells (ESCs) are pluripotent, meaning they can give rise to every cell type in the fully formed body, except the placenta and umbilical cord. Our bodies have an estimated 37 trillion cells, all of which originate from ESCs.

These cells are incredibly valuable because they provide a renewable resource for studying normal development and disease, and for testing drugs and other therapies. Human embryonic stem cells have been derived primarily from blastocysts created by in vitro fertilization (IVF) for assisted reproduction that were no longer needed. While ESCs are the most versatile mother cells for every cell in the body, host immune rejection is a complication that often occurs with stem cell transplantation. iv. Induced Pluripotent Stem Cells (aka Adult Stem Cells) Induced pluripotent stem cells (IPSCs) are the most widely publicized stem cells in today’s media. IPSCs have been engineered in the lab by converting tissue-specific cells, such as skin cells into cells that behave like embryonic stem cells. IPSCs have become critical tools to help scientists learn more about normal development and disease onset and progression, and they are also useful for developing and testing new drugs and therapies. While IPSCs share many of the same characteristics of embryonic stem cells, including the ability to give rise to all the cell types in the body, they aren’t exactly the same. Scientists are exploring what these differences are and what they mean. For one thing, the first IPSCs were produced by using viruses to insert extra copies of genes into tissue-specific cells.

Researchers are experimenting with many alternative ways to create IPSCs so that they can ultimately be used as a source of cells or tissues for medical treatments. IPSCs are derived from patient’s own skin or muscle cells. Thus, these types of cells avoid immune rejection challenges of embryonic stem cells. PROS AND CONS OF STEM CELL THERAPY PROS Because of their ability to self-renew, stem cells have an enormous potential to treat spinal cord injury, brain disorders, cardiac failure, cancer, diabetes and many other diseases. There is a lot of potential to replace the damaged and diseased tissues in the body. The stem cell research can allow the scientists to test a number of potential medicines and drugs without carrying out any test on animals and humans. The drug can be tested on a population of cells directly. The stem cell therapy also allows researchers to study the developmental stages that cannot be known directly through the human embryo and can be used in the treatment of a number of birth defects, infertility problems and also pregnancy loss. A higher understanding will allow the treatment of the abnormal development in the human body. CONS Stem cells have not yet been shown to slow the underlying disease nor do they improve motor symptoms of Parkinson’s patients. They can replace the need for levodopa drugs (Madolyn Bowman Rogers, Alzforum Networking for a Cure, June 17, 2014). Tumorigenicity as a Clinical Hurdle for Pluripotent Stem Cell Therapies [Nature Medicine, 19 (8), 998 (2013); J. Clin. Med., 4, 159 (2015)] Pluripotent stem cells (PSCs), including embryonic (ESCs) and induced pluripotent stem cells (iPSCs), offer immense potential as a source for regenerative therapies, as was recently recognized by the 2012 Nobel Committee in Medicine. However, the intrinsic qualities of self-renewal and pluripotency that make these cells so therapeutically promising are also responsible for an equally fundamental tumorigenic potential. In this regard, PSC tumorigenicity (producing or tending to produce tumors; also, carcinogenic) can ultimately be divided into two separate categories: malignant transformation of differentiated PSCs and benign teratoma (a tumor composed of tissues not normally present at the site) formation from residual undifferentiated PSCs, of which either can produce tumors consisting of one or all three germ layers, respectively. The risks of Pluripotent stem cells tumorigenicity have been highlighted over the past several years in a number of small and large animal studies, including preclinical dose-escalation tests for the first-in-human PSC clinical trial to be approved by the FDA in 2009.

In this case, mice that received the Geron human ESC-derived neural progenitor cell (NPC) product GRNOPC1 developed cysts in regenerating tissue sites of the spine, prompting a one-year moratorium on the trial even before the first patient received treatment. Other animal studies utilizing ESC- and iPSC-based therapies have shown further risk for PSC tumorigenic potential in humans. These include development of neural overgrowths and tumors from human ESC-derived dopaminergic neurons and NPCs transplanted into small animals, as well as ocular tumors in mice receiving ESC-derived retinal progenitors. Moving one step further into primate models, human ESC-derived dopaminergic neurons transplanted into the brains of Parkinsonian monkeys have also resulted in tumors. While PSC-derived tumors have yet to be reported in humans, several case studies have documented the formation of tumors in patients receiving fetal and adult stem cell treatments. These developments include the brain of a 12-year old boy who received fetal neural stem cell transplantation for treatment of ataxia telangiectasia, and the kidney of a 46-year old woman who received autologous hematopoietic stem cell transplantation for treatment of lupus nephritis”.

Stem Cell Contamination Stem cell lines used for research are not always ‘pure’ because their exposure to other animal cells to maintain viability results in contamination. Many animal cells contain microscopic microbes and diseases that are undetectable and contaminate human embryonic stem cells used for research. Older stem cell lines that are approved for use are also not as ‘fresh’ and may therefore develop genetic dysfunctions due to their age. As they proliferate, these genetic abnormalities then put the cells at risk for developing into a tumor. Used in a stem cell transplant, the ramifications could potentially be very dangerous. Invasive  Stem cell transplantation in the brain is an invasive procedure with risk of infections. Intravenously Injected Stem Cells Do not Reach the Central Nervous System (CNS) Intravenously administered stem cells do not cross the blood-brain barrier to reach the CNS. Patients would be wise not to waste money, as much as $30,000 per treatment, to have stem cells injected in them intravenously. ICBII has developed the world’s first and only technology to cross the blood-brain-barrier (BBB) for diagnosing and altering debilitating diseases like Parkinson’s and Alzheimer’s. IMAGINE a world with no Parkinson’s or Alzheimer’s disease. JUST IMAGINE...