Bigildeev Aleksei, Bigildeev Evgeny, Bulygina Eugenia, Tsygankova Svetlana, Gusakova Mariia, Illarionova Olga
Laboratory of epigenetic regulation of hematopoiesis, National Medical Research Center for Hematology, Russian Federation (Russia), Novii Zikovskii proezd, 4, Moscow, Russia, 125167.
Department of Medical and Biological Physics, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), ul. Trubetskaya, 8, Stroenie 2, Moscow, Russia, 119991.
Sci Rep. 2025 Jul 1;15(1):22295. doi: 10.1038/s41598-025-07709-9.
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. We hypothesized that a necessary condition for successful MSCs 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 BM 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 is prior damage to the recipient's BM stroma. Development of protocols of MSCs and HSCs co-transplantation, when full donor chimerism of hematopoietic and stromal tissue will be observed in recipient BM, is feasible. It will allow to increase the efficiency of therapy of malignant and other diseases of blood system, for which allogeneic BM transplantation is indicated, as well as patients with impaired stroma function such as osteogenesis imperfecta and congenital generalized lipodystrophy.
同种异体间充质干细胞（MSCs）的可移植性，即其稳定植入并参与骨髓（BM）基质的生理更新，仍然是一个悬而未决的问题。我们假设，MSCs移植成功的一个必要条件是受体的BM基质事先受到显著损伤。为了验证这一点，将来自雄性B10小鼠的骨髓静脉注射到接受6.5 Gy和13 Gy照射的同基因雌性小鼠以及未照射的个体中。我们通过RQ-PCR在受体骨骼照射30天后测量供体嵌合率，并通过ddPCR在BM CFU-Fs中测量。来自单拷贝Y染色体连锁的Prssly基因和常染色体Gapdh基因的PCR信号比值用于确定供体嵌合率。在研究的BM亚群中，未照射的受体均未发现供体细胞。在接受6.5 Gy照射的受体组中，仅在一只动物的BM中检测到0.16%的供体细胞。增加辐射剂量导致BM基质细胞中供体嵌合率显著增加：在该组两只存活的动物中分别为11%和14%。在15个样本中，未照射受体的骨骼中均未观察到供体嵌合率。在接受6.5 Gy照射的受体的18块骨骼中，仅在2块骨骼中检测到供体嵌合率（0.8%和1%）。接受13 Gy照射的受体骨骼中的供体嵌合率中位数为15%。我们得出结论，供体基质祖细胞成功植入的条件是受体的BM基质事先受到损伤。当在受体BM中观察到造血和基质组织的完全供体嵌合时，开发MSCs和HSCs共移植方案是可行的。这将提高恶性和其他血液系统疾病（对于这些疾病，同种异体BM移植是适用的）以及基质功能受损的患者（如成骨不全症和先天性全身性脂肪营养不良患者）的治疗效率。
