ROAD TO THE CURE UPDATE SEPTEMBER 2014 · Parkinson's Resource Organization

ROAD TO THE CURE UPDATE SEPTEMBER 2014

Category: Road to the Cure

Human stem cells, also known as pluripotent stem cells (PSCs), are cells with unlimited potential for self-renewal and pluripotent differentiation. The stem cells come from any organ (heart, lung, liver, etc.) or from the fetus of a pregnant female. The name “Pluripotent Stem Cells”is given to these cells due to their ability to form all cells in the body. The pluripotent stem cells can be embryonic or induced pluripotent stem cells (iPSCs).

Embryonic stem cells (ESCs), derived from embryos, exist only in the earliest stages of embryonic development and go on to form all cells of the adult body. In humans, these cells no longer exist after 5–6 days of development. The so-called “adult stem cells”are the special cells found in the tissues of adults, children and fetuses. They exist in most of the body tissues such as skin, blood, brain bone marrow, and can produce any of the red or white cells of the human blood system. Stem cells in the brain can form all the neurons and support cells of the brain. Unlike embryonic stem cells, adult stem cells cannot be indefinitely grown in the lab.

Tumorigenicity of Stem Cells

Induced pluripotent stem cells (iPSs) are cells taken from any tissue (for example: skin) that have been genetically modified to behave like embryonic stem cells (ESCs). Due to their immense potential for regenerative therapies, these cells have been the subject of discussions in newspapers, TV stations and radio shows for the last many years. Hundreds of millions of dollars have been poured into research by philanthropists, pharmaceutical companies and governments all over the world. However, the unique quality of self-renewal and pluripotency that make these iPSCs so therapeutically promising are also responsible for an equally fundamental TUMORIGENIC potential. For a detailed review, please see Nature Medicine, 19 (8), 998 (2013).

The tumorigenic risk of pluripotent stem cells has 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 approved by the US FDA in 2009. In this case, mice treated with human embryonic stem cell-derived neural progenitor cells developed cysts in regenerating tissue sites of the spine [Nature Biotech, 27, 877 (2009)].

Other animal studies using ESC- and iPSC-based therapies have shown further risk for tumorigenic potential. These include:

Development of neural overgrowths and tumors from human ESC-derived dopaminergic neurons

Ocular tumors in mice that received ESC-derived retinal progenitors

Human ESC-derived dopaminergic neurons transplanted into the brains of Parkinsonian monkeys have resulted in the formation of tumors [Stem Cells, 30, 935(2012)]

Development of tumors in the brain of 12-year old boy who received fetal neural stem cell transplantation for treatment of ataxia telangiectasia [Plos Med, 6, e1000029 (2009)]

Tumor development in the kidney of a 46-year old woman who received autologous hematopoietic stem cell transplantation for the treatment of lupus nephritis [Nature, 465, 997 (2010)]

Thus, on one side there is a tremendous promise of a new era for regenerative medicine, and on the other side is the risk of tumors, an unfortunate occurrence that would certainly slow the progress in the field of stem cells. In other words, stem cell therapy may not be available for many years.

Philanthropists, pharmaceutical companies, governments and patients will be wise for keeping an open mind for alternative approaches such as the one being developed by ICB International, Inc., La Jolla, CA. The Company is focused upon developing therapies to clear the brain of misfolded proteins/toxins to create healthy environment for regeneration of neurons and for surviving neurons to perform their normal function. For stem cell therapy to work for patients afflicted by neurodegenerative disorders such as Parkinson’s disease, the brain must be clear of toxins that have either killed neurons and/or compromised their function. When researchers have solved the quality and tumorigenic problems of stem cells, the combination of ICBI therapy with stem cell therapy is likely to create the healthiest environments for function of surviving and regeneration of neurons.

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Updated: August 16, 2017