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As a systemic inflammatory disorder, GVHD arises when donor T cells recognize the recipient\u2019s alloantigens and initiate an immune attack. Currently, effective second-line treatment options remain scarce for patients with antibiotic-resistant or steroid-refractory GVHD. Mesenchymal stem cells (MSCs) are non-hematopoietic cells widely distributed in fetal and adult tissues and organs, endowed with multipotent differentiation potential and prominent immunomodulatory properties. Emerging evidence suggests that impaired function or apoptosis of MSCs exacerbates HSCT-associated complications and significantly compromises hematopoietic stem cell engraftment. Over the past two decades, leveraging their potent anti-inflammatory and immunomodulatory capacities, MSCs have been rapidly integrated into HSCT research and clinical practice, where they play a pivotal role in promoting hematopoietic engraftment and preventing or treating GVHD. This review elaborates on the molecular basis of MSCs\u2019 anti-inflammatory effects and the inflammatory pathological characteristics of HSCT-related complications. We conducted a systematic literature search in PubMed, Web of Science, and Embase databases up to December 2025. The search strategy combined the following terms: (\u201cmesenchymal stem cells\u201d OR \u201cMSCs\u201d) AND (\u201chematopoietic stem cell transplantation\u201d OR \u201cHSCT\u201d) AND (\u201cgraft-versus-host disease\u201d OR \u201cGVHD\u201d) AND (\u201cinflammation\u201d OR \u201cimmune regulation\u201d). It systematically analyzes the molecular mechanisms underlying MSCs\u2019 anti-inflammatory actions and their application progress in HSCT, aiming to provide a theoretical foundation and translational insights for the rational clinical application of MSCs in HSCT.<\/jats:p>","DOI":"10.1177\/09636897261440416","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:32:41Z","timestamp":1775802761000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["The anti-inflammatory effects of mesenchymal stem cells and their research progress in hematopoietic stem cell transplantation: A comprehensive review"],"prefix":"10.1177","volume":"35","author":[{"given":"Changling","family":"Zhu","sequence":"first","affiliation":[{"name":"Graduate School of Bengbu Medical University, Bengbu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Ma","sequence":"additional","affiliation":[{"name":"Graduate School of Bengbu Medical University, Bengbu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wangfu","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Medicine, Anhui University of Science and Technology, Huainan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4223-5532","authenticated-orcid":false,"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of hematology, Anhui No. 2 Provincial People\u2019s Hospital (Affiliated Hospital of Anhui Second Medical college), Hefei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of hematology, Anhui No. 2 Provincial People\u2019s Hospital (Affiliated Hospital of Anhui Second Medical college), Hefei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-024-04126-z"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024013442"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2023.5757"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.5125\/jkaoms.2023.49.6.311"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajco.13332"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2018.036"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/mrcr\/rxac086"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/08850666231200193"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03587-y"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052425"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.637725"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2020.100948"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13759"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2024.102709"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02313-9"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nsa.2024.104061"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2022.05.012"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-024-03980-1"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01034-9"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.01.009"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01201-6"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02124-y"},{"issue":"12","key":"e_1_3_3_24_2","first-page":"1899","article-title":"Inflammation and tumor microenvironment","volume":"48","author":"Niu T","year":"2023","unstructured":"Niu T, Zhou F. 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