Preliminary high-dose irradiation of the recipient and associated damage of bone marrow stromal compartment enables bone marrow stroma transplantation
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. We hypothesized that a necessary condition for successful MSCs transplantation is the prior significant damag...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-07709-9 |
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| author | Aleksei Bigildeev Evgeny Bigildeev Eugenia Bulygina Svetlana Tsygankova Mariia Gusakova Olga Illarionova |
| author_facet | Aleksei Bigildeev Evgeny Bigildeev Eugenia Bulygina Svetlana Tsygankova Mariia Gusakova Olga Illarionova |
| author_sort | Aleksei Bigildeev |
| collection | DOAJ |
| description | 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. 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. |
| format | Article |
| id | doaj-art-58c048a42a3f44f5bd9e983e011c2c1c |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-58c048a42a3f44f5bd9e983e011c2c1c2025-08-20T04:01:26ZengNature PortfolioScientific Reports2045-23222025-07-0115111010.1038/s41598-025-07709-9Preliminary high-dose irradiation of the recipient and associated damage of bone marrow stromal compartment enables bone marrow stroma transplantationAleksei Bigildeev0Evgeny Bigildeev1Eugenia Bulygina2Svetlana Tsygankova3Mariia Gusakova4Olga Illarionova5Laboratory of epigenetic regulation of hematopoiesis, National Medical Research Center for Hematology, Russian Federation (Russia)Consulting Company “ARB-Consulting”Eukaryotic Genomics Laboratory, National Research Center “Kurchatov Institute”Eukaryotic Genomics Laboratory, National Research Center “Kurchatov Institute”Eukaryotic Genomics Laboratory, National Research Center “Kurchatov Institute”Laboratory of Cellular and Molecular Basis of Histogenesis, Koltzov Institute of Developmental Biology of the Russian Academy of SciencesAbstract 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.https://doi.org/10.1038/s41598-025-07709-9MSCsMSC transplantationCFU-FBone marrow stroma transplantationIrradiationDonor’s chimerism |
| spellingShingle | Aleksei Bigildeev Evgeny Bigildeev Eugenia Bulygina Svetlana Tsygankova Mariia Gusakova Olga Illarionova Preliminary high-dose irradiation of the recipient and associated damage of bone marrow stromal compartment enables bone marrow stroma transplantation Scientific Reports MSCs MSC transplantation CFU-F Bone marrow stroma transplantation Irradiation Donor’s chimerism |
| title | Preliminary high-dose irradiation of the recipient and associated damage of bone marrow stromal compartment enables bone marrow stroma transplantation |
| title_full | Preliminary high-dose irradiation of the recipient and associated damage of bone marrow stromal compartment enables bone marrow stroma transplantation |
| title_fullStr | Preliminary high-dose irradiation of the recipient and associated damage of bone marrow stromal compartment enables bone marrow stroma transplantation |
| title_full_unstemmed | Preliminary high-dose irradiation of the recipient and associated damage of bone marrow stromal compartment enables bone marrow stroma transplantation |
| title_short | Preliminary high-dose irradiation of the recipient and associated damage of bone marrow stromal compartment enables bone marrow stroma transplantation |
| title_sort | preliminary high dose irradiation of the recipient and associated damage of bone marrow stromal compartment enables bone marrow stroma transplantation |
| topic | MSCs MSC transplantation CFU-F Bone marrow stroma transplantation Irradiation Donor’s chimerism |
| url | https://doi.org/10.1038/s41598-025-07709-9 |
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