{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T20:10:14Z","timestamp":1785874214770,"version":"3.56.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic foot ulcers (DFUs) represent a debilitating complication of diabetes characterized by high rates of morbidity and mortality, yet conventional management often yields limited efficacy. Although cell-based therapies offer a promising therapeutic avenue, their clinical efficacy and optimal target populations remain to be definitively established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched databases including PubMed, Embase, the Cochrane Library, Web of Science, and the China National Knowledge Infrastructure from inception to November 2025 for randomized controlled trials (RCTs). Study quality was assessed using the Revised Cochrane risk-of-bias tool for randomized trials. Meta-analysis, subgroup analysis, and heterogeneity analysis were performed using R software (version 4.3.3). Sensitivity analysis was conducted via the leave-one-out method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty-two RCTs involving 2059 patients were included, assessing nine core outcomes including ulcer healing rate and amputation rate. Pooled analysis demonstrated that cell therapy significantly improved the ulcer healing rate (OR = 4.64, 95% CI: 3.11 to 6.90), reduced the amputation rate (OR = 0.29, 95% CI: 0.18 to 0.49), enhanced limb perfusion (ABI MD = 0.14, 95% CI: 0.05 to 0.22; TcPO\n                      <jats:sub>2<\/jats:sub>\n                      MD = 11.58, 95% CI: 5.36 to 17.80), alleviated pain (resting pain score MD = -1.04, 95% CI: -1.49 to -0.59), reduced ulcer area (MD = -2.15, 95% CI: -3.74 to -0.56), and shortened healing time (MD = -16.83 days, 95% CI: -27.93 to -5.74). Subgroup analyses revealed: 1) Cell Type: Autologous bone marrow-derived mesenchymal stem cells (BMMSCs) yielded the most favorable outcomes (ulcer healing OR = 8.33,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.01). 2) Administration Protocol: A medium-to-high dose range combined with intramuscular injection was identified as optimal. Specifically, high and very-high doses demonstrated the strongest efficacy in critical limb salvage outcomes (amputation and healing rates), while the medium-dose regimen exhibited the most robust statistical consistency across all secondary metrics (e.g., ulcer area reduction). 3) Target Population: Patients with shorter diabetes duration (&amp;lt;10 years), larger ulcer area (\u226510 cm\u00b2), or prolonged non-healing ulcers (&amp;gt;200 days) derived more significant benefit.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Cell therapy shows significant potential as an adjuvant treatment for DFUs. Current evidence suggests that a protocol utilizing autologous BMMSCs within a medium-to-high dose range (targeting 1\u00d710\n                      <jats:sup>7<\/jats:sup>\n                      to 1.2\u00d710\n                      <jats:sup>9<\/jats:sup>\n                      cells) via intramuscular injection may optimize therapeutic efficacy while ensuring clinical feasibility. Exploratory findings indicate that this strategy might be particularly suitable for patients with large, refractory DFUs and short diabetes duration, though these observations require further validation in large-scale trials.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/<\/jats:ext-link>\n                      , identifier CRD420251247289.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1763071","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:32:25Z","timestamp":1773120745000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Bone marrow-derived mesenchymal stem cells combined with intramuscular injection promote the healing of diabetic foot ulcers: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Xuliu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guobin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"You","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijing","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiran","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, 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