“Matchmaker, Matchmaker, make me at match…”
The ability to transplant cells, tissues or organs is limited by Major Histocompatibility Complex (MHC) compatibility between donor and recipient. If there is a perfect match between all MHC antigens, the transplant is accepted. If all the MHC antigens are mismatched, the transplant is rejected. In humans the MHC is called human leucocyte antigen (HLA). The more HLA antigens shared, the better the chance for a successful transplantation outcome.
Sometimes called transplantation antigens, HLA antigens are proteins found on the surface of most cells and tissues in the body. These antigens play critical roles in the immune system’s defense against microbial invaders as well as being the component of the immune system that recognizes a donor’s HLA antigens as foreign, thus causing rejection.
Finding an HLA-match donor can be extremely difficult. This is because there are different classes of HLA and many different antigens within these classes. To further complicate the issue, a person inherits one of each antigen from each parent. Another layer of complication is the vast number of possible combinations of these antigens, which numbers in the billions.
Morphogenesis Allograft Tissue with Compatible HLA (MATCH) is another innovative technology being developed at Morphogenesis. MATCH is designed to obviate the need to sort through billions of donors or at the other extreme, a lifelong dependence on immunosuppressive drugs required to subdue the constant battle by the recipient’s immune system to reject the ‘invading’ donor cells. The purpose of MATCH is to generate banks of multi-potential stem cells with limited and predetermined expression of specific antigens that cause graft rejection. Stem cells, whether mesenchymal stem cells, placental cord blood stem cells, hematopoietic stem cells or embryonic stem cells, are genetically reprogrammed within the HLA region. MATCH alters the tissue compatibility of a stem cell by deleting the HLA genes and then replacing the genetic locus with predetermined variations (haplotypes).
Cells, tissues and organs generated by MATCH will have the advantage of being able to overcome immune rejection without jeopardizing their ability to present antigens to combat pathogenic organisms. This genetic approach to cell therapy and tissue transplantation could ultimately resolve the donor shortage and transplant rejection issues in a scientifically feasible, socially acceptable, and economically viable manner by creating a “supermarket” of cell genotypes, which will be compatible with virtually any person needing cells or tissue to replace diseased or damaged organs.
Growth factors are proteins that bind to receptors on the cell surface with the primary result of activating cellular proliferation and/or differentiation. Many growth factors are quite versatile; some stimulate cellular division in numerous different cell types while others are specific to a particular cell-type. These protein factors or cytokines are produced with increasing yields and purity in their recombinant form for use as therapeutic drugs. Stem Cell Proliferation Factor, SCPF, is a growth factor that stimulates stem cells to proliferate. That SCPF has been shown to expand hematopoietic, mesodermal and mesenchymal stem cells to proliferate without differentiating, while maintaining their multi-potentiality, makes SCPF a powerful adjunct to Morphogenesis MATCH technology.
One of the characteristics of stem cells, whether embryonic, hematopoietic, pancreatic, etc. is their rarity. Stem cells are currently grown using a combination of cytokines, however, these cytokine cocktails do not keep cells in their primitive state and reproduction of results is difficult. The ability to expand the number of stem cells obtained from a stem cell harvest using SCPF will increase the therapeutically beneficial number of these cells; allow them to be maintained in culture for extended periods of time and allow genetic manipulation to treat diseases such as Sickle Cell Disease and many others.
The ability to utilize stem cells in the development of cellular therapies is predicated upon the ability to identify and isolate the cells of interest from complex tissues and mixtures of cells. Morphogenesis is developing its PACS device which is not only capable of capturing circulating tumor cells to be used in the development of personalized ImmuneFx cancer vaccines, PACS will also provide stem cells from mobilized peripheral blood for expansion using SCPF and genetic manipulation using MATCH to produce ‘matching’ cells for transplantation.