{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T20:00:29Z","timestamp":1780344029564,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T00:00:00Z","timestamp":1747440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute radiation syndrome (ARS) results from high-dose ionizing radiation (IR) exposure, with bone marrow (BM) being highly susceptible due to its proliferative activity. BM injury causes pancytopenia, leading to infections, anemia, and bleeding. Mesenchymal stem cells (MSCs) hold promise for ARS treatment because of their immunomodulatory, anti-inflammatory, and regenerative properties. However, challenges such as replicative senescence, poor survival, and engraftment in irradiated microenvironments limit their efficacy. This study evaluated rapamycin-preconditioned placenta-derived MSCs (rPD-MSCs) in a mouse ARS model. Rapamycin was selected for preconditioning due to its ability to induce autophagy and modulate cytokine secretion. We assessed rapamycin-dependent modulation of autophagy-related genes and proteins, as well as hematopoietic cytokines secretion in PD-MSCs, and evaluated morphological changes in blood and BM at 7 and 21 days post-irradiation in ICR\/CD1 mice. Preconditioning with rapamycin alters the secretion of granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), and Fms-related tyrosine kinase 3 ligand (Flt3LG) in PD-MSCs without affecting cell viability. rPD-MSCs better enhance hematopoietic recovery, restore bone marrow cellularity, and increase peripheral blood cell counts by elevating the secretion of hematopoietic cytokines compared to non-preconditioned cells. These results highlight rapamycin preconditioning as a promising strategy to enhance MSCs therapeutic potential for ARS, supporting further preclinical and clinical exploration.<\/jats:p>","DOI":"10.3390\/ijms26104804","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T07:34:03Z","timestamp":1747640043000},"page":"4804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Preconditioning with Rapamycin Improves Therapeutic Potential of Placenta-Derived Mesenchymal Stem Cells in Mouse Model of Hematopoietic Acute Radiation Syndrome"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3967-0442","authenticated-orcid":false,"given":"Vasilii","family":"Slautin","sequence":"first","affiliation":[{"name":"Laboratory of Enteric Viral Infections, Federal Scientific Research Institute of Viral Infections \u00abVirome\u00bb, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Yekaterinburg 620030, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7475-9517","authenticated-orcid":false,"given":"Vladislav","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Ural State Medical University, Yekaterinburg 620014, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandr","family":"Bugakov","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Ural State Medical University, Yekaterinburg 620014, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6137-5437","authenticated-orcid":false,"given":"Anna","family":"Chernysheva","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Viral Infections, Federal Scientific Research Institute of Viral Infections \u00abVirome\u00bb, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Yekaterinburg 620030, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Gavrilov","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Ural State Medical University, Yekaterinburg 620014, Russia"},{"name":"Laboratory of Anti-Aging Technologies, Institute of Medical Cell Technologies, Yekaterinburg 620026, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6895-7947","authenticated-orcid":false,"given":"Irina","family":"Maklakova","sequence":"additional","affiliation":[{"name":"Laboratory of Anti-Aging Technologies, Institute of Medical Cell Technologies, Yekaterinburg 620026, Russia"},{"name":"Department of Physiology, Ural State Medical University, Yekaterinburg 620014, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Bazarnyi","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Clinical Laboratory Diagnostics, Ural State Medical University, Yekaterinburg 620014, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Grebnev","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Ural State Medical University, Yekaterinburg 620014, Russia"},{"name":"Laboratory of Anti-Aging Technologies, Institute of Medical Cell Technologies, Yekaterinburg 620026, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Kovtun","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Ural State Medical University, Yekaterinburg 620014, Russia"},{"name":"Department of Physiology, Ural State Medical University, Yekaterinburg 620014, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s40778-020-00176-0","article-title":"Use of MSCs and MSC-Educated Macrophages to Mitigate Hematopoietic Acute Radiation Syndrome","volume":"6","author":"Chinnadurai","year":"2020","journal-title":"Curr. 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