(W1254) DAMAGE TO BONE MARROW STROMA INDUCED BY GAMMA-RADIATION OF A RECIPIENT IS A PREREQUISITE FOR ENGRAFTMENT OF DONOR’S MSCS INJECTED INTRAVENOUSLY

Abstract: Transplantability of allogeneic mesenchymal stem cells (MSCs) as a stable engraftment and participation in physiological renewal of bone marrow (BM) stroma remains an open question. Successful MSCs transplantation could be beneficial to patients with leukemia, in which BM stroma is modified by leukemic cells, supports their survival and provide them drug resistance. Replacement of BM stroma with healthy one from a donor could also be a saving opportunity for those with genetic disorders of connective tissues such as osteogenesis imperfecta. We hypothesized that a necessary condition for successful MSC transplantation is the prior significant damage to the recipient’s BM stroma. To test this, BM derived from male B10 mice was injected intravenously into syngeneic female mice irradiated with 6.5 Gy and 13 Gy, and unirradiated individuals. We measured donor chimerism 30 days after irradiation in recipients’ bones by RQ-PCR and in BM CFU-Fs by ddPCR. The ratio of PCR signals from single-copy Y chromosome-linked Prssly gene and autosomal Gapdh gene was used to determine donor chimerism. None of the non-irradiated recipients had donor cells in the subpopulation under study. In the group of recipients irradiated at a dose of 6.5 Gy, donor cells were detected at 0.16% in BM of only one animal. Increasing the radiation dose resulted in a significant increase in donor chimerism among BM stromal cells: it was 11% and 14% in two survived animals of this group. Donor chimerism in the bones of unirradiated recipients was not observed in any of the 15 samples. It was detected in only 2/18 bones of recipients irradiated with 6.5 Gy (0.8% and 1%). The median donor chimerism in bones of recipients irradiated with 13 Gy was 15%. We conclude that the condition for successful engraftment of donor stromal progenitor cells including MSCs is prior damage to the recipient's BM stroma.

Funding Source: This study is supported by Russian Science Foundation (project No 22-25-00459).

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