Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates

Abstract

Ex vivo-expanded mesenchymal stem cells (MSCs) were transduced with a green fluorescent protein (GFP) retroviral construct and subsequently infused into 3 adult baboons following lethal total body irradiation and hematopoietic support or without any prior conditioning. To study the long-term fate of these MSCs, necropsies were performed between 9 and 21 months following MSC infusion, and an average of 16 distinct tissues were recovered from each recipient and evaluated for the presence of the GFP transgene in purified genomic DNA by sensitive real-time polymerase chain reaction (PCR). Two baboons received autologous and one allogeneic GFP-transduced MSCs. Both allogeneic and autologous MSCs appeared to distribute in a similar manner. Gastrointestinal tissues harbored high concentrations of transgene per microgram of DNA. Additional tissues including kidney, lung, liver, thymus, and skin were also found to contain relatively high amounts of DNA equivalents. Estimated levels of engraftment in these tissues ranged from 0.1% to 2.7%. The nonconditioned recipient appeared to have less abundant engraftment. These data suggest that MSCs initially distribute broadly following systemic infusion and later may participate in ongoing cellular turnover and replacement in a wide variety of tissues.