Assessment of human MAPCs for stem cell transplantation and cardiac regeneration after myocardial infarction in SCID mice

Objective Clinical studies suggest that transplantation of total bone marrow (BM) after myocardial infarction (MI) is feasible and potentially effective However, focusing on a defined BM derived stem cell type may enable a more specific and optimized treatment Multilineage differentiation potential makes BM derived multipotent adult progenitor cells (MAPCs) a promising stem cell pool for regenerative purposes We analyzed the cardioregenerative potential of human MAPCs in a murine model of myocardial infarction Materials and Methods Human MAPCs were selected by negative depletion of CD45(+)/glyco phorin(+) BM cells and plated on fibronectin-coated dishes In vitro, stem cells were analyzed by reverse transcription polymerase chain reaction In vivo, we transplanted human MAPCs (5 x 10(5)) by intramyocardial injection after MI in severe combined immunodeficient (SCID) beige mice Six and 30 days after the surgical procedure, pressure-volume relationships were investigated in vivo Heart tissues were analyzed immunohistochemically Results Reverse transcription polymerase chain reaction experiments on early human MAPC passages evidenced an expression of Oct-4, a stem cell marker indicating pluripotency In later passages, cardiac markers (Nkx2 5, GATA4, MLC 2v, MLC 2a, ANP, cTnT, cTnI,) and smooth muscle cell markers (SMA, SM22 alpha) were expressed Transplantation of human MAPCs into the ischemic border zone after MI resulted in an improved cardiac function at day 6 (ejection fraction, 26% vs 20%) and day 30 (ejection fraction, 30% vs 23%) Confirmation of human MAPC marker vimentin in immunohistochemistry demonstrated that human MAPC Integrated in the pen Infarct region The proliferation marker Ki67 was absent in immunohistochemistry and teratoma formation was not found, indicating no tumorous potential of transplanted human MAPCs in the tumor sensitive SCID model Conclusions Transplantation of human MAPCs after MI ameliorates myocardial function, which may be explained by trophic effects of human MAPCs Lack of evidence of tumorous potential in the tumor-sensitive SCID model indicates that human MAPCs may deliver an effective and safe stem cell pool for potential treatment of ischemic heart disease (C) 2010 ISEH Society for Hematology and Stem Cells Published by Elsevier Inc