Imaging Human ES-Derived Cells: Defining Parameters for Safety in Regenerative Medicine.

Funding Type: 
Comprehensive Grant
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 
As outlined in Proposition 71, very many people in California and beyond suffer from devastating diseases and injuries that are currently incurable, including cancer, diabetes, heart disease, Alzheimer’s, Parkinson’s, spinal cord injuries, blindness and so on. It is has been shown that normal, healthy tissues are renewed and regenerated constantly from special cells, called tissue-specific stem cells, that reside in all tissues. Many of the diseases and conditions listed above are caused or are accompanied by the failure of normal tissue regeneration. It is believed that these conditions could be vastly improved, if not cured, if medical science could figure out a way to restore normal tissue regeneration. A very promising approach is to generate tissue-specific stem cells in the laboratory and transplant them into patients to replace failing tissue. Currently the best source for tissue-specific stem cells (in the following called “progenitors”) is to derive such cells by culturing human embryonic stem cells (hESC) in the laboratory under conditions that resemble those in the tissue of interest. Transplantation of hESC-derived progenitors has shown good responses in animal models of human disease such as diabetes and Parkinson’s. However, before such cells can be used in patients, many issues still have to be addressed. One fundamental issue is the safety of such therapies, particularly the very important concern that transplanted progenitors in the long-term could cause cancer in the recipient. This concern is based on studies of hESC and some progenitors that have been shown to cause cancer in animals. However there are also studies in which progenitors have survived and functioned in animals without causing cancer. It is not known why some progenitors lead to cancer whereas others do not. We have designed a study using state-of-the-art technology to identify for the first time in a systematic fashion what factors might cause progenitors to form cancer. We will study the fate of many different, well-characterized progenitors in mice that allow the growth of human cells. We will follow the fate of the injected cells over the life time of the mouse, approximately 1 year. Once we establish which of the different progenitors cause cancer and which do not, we will analyze the genes and other properties of these cells to determine which factors individually, or as a group, correlate with the development of cancers. The results of this study will be of fundamental importance for all physicians and scientists currently working to cure various diseases and conditions with stem cell therapies and for all patients and their loved ones who hope to benefit one day from such therapies.
Statement of Benefit to California: 
California, like much of the United States, is facing a staggering challenge to provide treatments for a population that is living longer than ever before. Increasingly physicians are treating chronic, debilitating, and therefore expensive diseases associated with aging. This is made all the worse by the demographic wave caused by the entry of the Baby Boomers into retirement. As a result, the percentage of the elderly in California is expected to grow from 14 percent in 1990 to 22 percent in 2030. (Source: California Department of Finance, Population Projections 1993). Many of the chronic devastating diseases of an aging population are the degenerative diseases. Generally speaking, degenerative diseases are those diseases caused by the loss or dysfunction of cells. Examples include osteoarthritis (loss of cartilage cells that protect the ends of the bones), Parkinson’s disease (the loss of dopaminergic neurons), osteoporosis (dysfunction of osteoblasts), macular degeneration (dysfunction of retinal pigment cells) and so on. More significantly, the loss or dysfunction of cells in the heart (or the vessels that supply the heart with blood) results in heart disease, the leading cause of death in California. In 2001 (the most recent year data is available) heart disease caused 68,234 deaths (29% of all the deaths in the state). Stroke is also a vascular disease and the third leading cause of death in California. Regenerative medicine represents the effort of cell biologists to provide a new approach to the problem of degenerative disease. Human embryonic stem cells (hESC) have the potential to become all of the cells in the human body, and their unique properties give researchers the hope that these primitive cells can result in new therapies. However, before hESC-derived cells can be used in the clinic, safety concerns must be addressed. The major concern regarding the transplantation of hESC-derived cell types is their potential to cause cancer. This study will illuminate the factors that contribute to the tumorigenicity of hESC-derived cells and will define parameters for their safe application in the clinic. Thus this study addresses a fundamental issue of all stem cell therapies rather than focuses on a disease specific application and therefore provides a universal resource for progress in regenerative medicine.

© 2013 California Institute for Regenerative Medicine