Cell-Based Regenerative Therapies: Role of Major Histocompatibility Complex-1 Antigen
Stem cell-based therapies hold promise for the treatment of various human diseases and disorders but also face hurdles that must be overcome to ensure their therapeutic success. Key issues determining the long-term outcome of stem cell therapies include improvements in the survival, engraftment, proliferation, and regeneration of transplanted cells. Although stem cells possess extensive replicative capacity and pluripotency that can be exploited for therapeutic use (Carpenter et al., 2009), immune rejection of donor cells by the host immune system post-transplantation is one of the most serious obstacles that must be cleared (Chidgey and Boyd, 2008). The majority of donor cell death occurs in the first hours to days after transplantation due to a combination of factors, including lack of matrix support to promote cell survival, exposure of transplanted cells to hypoxia/ischemia in host environment, and immune system-mediated cell death (Robey et al., 2008). Recent data have provided valuable insights as to why a majority of donor stem cells die in vivo, a phenomena that limits the efficacy and therapeutic potential of stem cell-based therapies. The expression of the major histocompatibility complex class I (MHC-I) molecules by donor stem cells has emerged as a key factor in determining whether or not a cell is targeted for host immune-mediated destruction post-transplantation (Bix et al., 1991) (Ma et al., 2010). The expression level of MHC-I not only depends on the source of the stem cells, such as embryonic versus adult stem cell populations, but also on the degree to which the cells have been manipulated prior to transplantation into host (Chidgey and Boyd, 2008). Such variation in MHC-I expression will influence the survival and engraftment potential post-transplantiation. Determining the mechanisms regulating donor graft tolerance by the host will be crucial for advancing the clinical application of stem cell-based therapies.
KeywordsStem cell therapies Transplantation Cell culture techniques MHC-I Embryonic stem cells Interferon-γ
- Au P, Daheron LM, Duda DG, Cohen KS, Tyrrell JA, Lanning RM, Fukumura D, Scadden DT, Jain RK (2008) Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels. Blood 111:1302–1305PubMedCrossRefGoogle Scholar
- Ma M, Ding S, Lundqvist A, San H, Fang F, Konoplyannikov M, Berry C, Beltran LE, Chen G, Kovacic JC, Boehm M (2010) Major histocompatibility complex-I expression on embryonic stem cell-derived vascular progenitor cells is critical for syngeneic transplant survival. Stem Cells 28:1465–1475PubMedCrossRefGoogle Scholar
- Swijnenburg RJ, Tanaka M, Vogel H, Baker J, Kofidis T, Gunawan F, Lebl DR, Caffarelli AD, de Bruin JL, Fedoseyeva EV, Robbins RC (2005) Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium. Circulation 112:1166–1172Google Scholar
- Tolar J, O’Shaughnessy MJ, Panoskaltsis-Mortari A, McElmurry RT, Bell S, Riddle M, McIvor RS, Yant SR, Kay MA, Krause D, Verfaillie CM, Blazar BR (2006) Host factors that impact the biodistribution and persistence of multipotent adult progenitor cells. Blood 107:4182–4188PubMedCrossRefGoogle Scholar