Immunogenicity of HLA-homozygous human parthenogenetic stem cells
A major problem facing stem cell therapy is immune rejection. Immune rejection occurs when the immune system of one person recognizes cells from another person as being “foreign” and rejects them. Foreign cells are recognized because they have a different "HLA-type". Stem cells being studied today are derived from individual persons. These cells are limited in their ability to be used to heal many people other than the individual stem cell donor because of immune rejection. Immune rejection could thus limit the future effectiveness and practicality of stem cell therapy. Immune rejection can be overcome by using drugs, but these drugs are powerful and can lead to bad side-effects.
If HLA-types are similar between two people, then immune rejection is reduced. This fact is the reason why doctors try to match the HLA-types between organ donors and recipients. However, an individual's HLA-type is very unique and complicated because it is composed of a mixture of HLA-types from their mother and their father. This complexity is why it is difficult for doctors to find matching donors with similar HLA-types for their patients in need of an organ or tissue transplant.
Human “parthenogenetic stem cells” (hpSC) have qualities that may allow them to be used in stem cell therapy by large segments of the population with little or no immune rejection. Parthenogenetic stem cells are derived from unfertilized human eggs and thus have no HLA-type contribution from a man. This fact makes the HLA-type of a hpSC much less complicated and easier to match to many people. HLA-matched parthenogenetic stem cells could allow the creation of a bank of HLA-matched hpSC that could be used to treat disease in hundreds of millions of persons with a reduced chance of immune rejection and a reduced need to use immune-suppressing drugs.
Our previous work has resulted in the creation of ten hpSC lines, one line has the most common HLA-haplotype found in the US and can be immune-matched to millions of persons across the world. The hpSC have been shown to have very similar qualities to embryonic stem cells. We have also shown that as with embryonic stem cells, hpSC can change, or “differentiate” into cells that may have therapeutic value.
This research proposal will develop data to prove or disprove the idea that hpSC may avoid immune rejection if they are used for cell therapy in a HLA-matched patient. The research will study the expression of HLA-types in hpSC and will study how immune cells donated by people with matching HLA-types react to these cells in laboratory tests.
This project will benefit California by providing research data to evaluate a unique type of human pluripotent stem cell that may solve the immune rejection problem, one of the most serious barriers to regenerative medicine. These unique stem cells, called human parthenogenetic stem cells, are created from unfertilized human eggs and have a quality that allows immune-matching to millions of persons of differing sexes and racial backgrounds.
Immune matching (or "HLA matching") is used in organ and bone marrow transplants today to reduce immune rejection. If this research shows that immune-matched parthenogenetic stem cells can also reduce or eliminate immune rejection, it would open the door for the establishment of an “immune-matched” stem cell bank. Such a bank of parthenogenetic stem cells with common immune types (called HLA-types) could increase the utility and availability of therapeutic cells and decrease their cost by allowing clinicians to match cells to their patients for many different diseases where stem cell therapy may prove to be beneficial.
A California-based immune-matched parthenogenetic stem cell bank could be a resource used in research and therapeutic applications worldwide in cases where stem cells or their derivatives are studied or needed to cure disease. Intellectual property could be created for California through this resource, resulting in increased valuation for California research organizations and an associated increase in investment, employment and tax revenues.
California scientists are now working intensively with human stem cells because of their great potential to cure many intractable diseases including diabetes, liver disease, retinal disease, Alzheimer’s disease, muscular dystrophy and Parkinson’s disease, to name but a few. Existing parthenogenetic stem cell lines have been shown to produce cell types that may have application in treating several of these diseases. One of these existing lines expresses the most common immune-type found within the U.S. population and thus may have therapeutic utility for millions of Californians. The goal of this research is not only to study the ability of these existing cells to avoid immune rejection, but to create additional parthenogenetic stem cell lines in California under "clinical standards", thus providing a larger database of knowledge as to their potential therapeutic utility and increasing the number of these cells that may eventually be available for clinical use.