{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T01:46:55Z","timestamp":1785030415937,"version":"3.55.0"},"reference-count":31,"publisher":"Georg Thieme Verlag KG","issue":"07","funder":[{"name":"Jiangxi Provincial Science Technology Foundation of China","award":["No.20151BBG70073"],"award-info":[{"award-number":["No.20151BBG70073"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Funds of China","doi-asserted-by":"crossref","award":["81760168"],"award-info":[{"award-number":["81760168"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Funds of China","doi-asserted-by":"crossref","award":["81560154"],"award-info":[{"award-number":["81560154"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Funds of China","doi-asserted-by":"crossref","award":["81460018"],"award-info":[{"award-number":["81460018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\nAim Diabetic foot has become the main cause of non-traumatic amputation. Stem cell therapy, especially mesenchymal stem cells (MSCs), holds a great promise as a therapy for diabetic foot with ischemia limb arterial disease. The aim of this pilot study is to evaluate the safety and efficacy of placenta-derived MSCs (P-MSCs) treatment for diabetic patients with critical limb ischemia (CLI).<\/jats:p><jats:p>\nMethods Four eligible diabetic patients with CLI were consecutively enrolled in this pilot study. On the base of the standard-of-care treatment, these patients accepted P-MSCs treatment by intramuscular injection for successive 3 times at an interval of 4 weeks, and the safety and efficacy of placenta-derived MSCs (P-MSCs) treatment were evaluated.<\/jats:p><jats:p>\nResults There were no serious adverse events during the period of P-MSCs injection and the 24-weeks follow-up period. The clinical ischemic features of patients were improved 24 weeks after P-MSCs treatment. The scores of resting pain and limb coldness significantly decreased, and pain-free walking distance significantly increased from baseline to 24 weeks after P-MSCs therapy. The resting ankle brachial index increased, but no statistically significant difference was found. The findings of magnetic resonance angiography showed the increase of collateral vessel formation in one patient, but there were no significant changes observed in the other patients.<\/jats:p><jats:p>\nConclusions The data in this pilot study indicated that multiple intramuscular P-MSCs injections may be a safe and effective alternative therapy for diabetic patients with CLI, and larger, placebo-controlled, perspective studies are needed to prove these results.<\/jats:p>","DOI":"10.1055\/a-0978-4972","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T22:54:30Z","timestamp":1565823270000},"page":"542-548","source":"Crossref","is-referenced-by-count":18,"title":["Safety and Efficacy of Placenta-Derived Mesenchymal Stem Cell Treatment for Diabetic Patients with Critical Limb Ischemia: A Pilot Study"],"prefix":"10.1055","volume":"129","author":[{"given":"Jiao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Xia","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Cell biology, Medical College of Nanchang University, Nanchang, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Bo","family":"Han","sequence":"additional","affiliation":[{"name":"The Stem Cell Engineering Research Center of Jiangxi Province, Shangrao, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Yan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Xiong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2019,8,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"891","DOI":"10.2337\/dc17-2210","article-title":"Limb- and person-level risk factors for lower-limb amputation in the prospective seattle diabetic foot study","volume":"41","author":"E J Boyko","year":"2018","journal-title":"Diabetes Care"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.2337\/dc12-0200","article-title":"Long-term prognosis of diabetic foot patients and their limbs: Amputation and death over the course of a decade","volume":"35","author":"S Morbach","year":"2012","journal-title":"Diabetes Care"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.jvs.2018.01.066","article-title":"A systematic review and meta-analysis of revascularization outcomes of infrainguinal chronic limb-threatening ischemia","volume":"68","author":"J Almasri","year":"2018","journal-title":"Journal of Vascular Surgery"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1002\/bjs.10292","article-title":"Comparison of angioplasty and bypass surgery for critical limb ischaemia in patients with infrapopliteal peripheral artery disease","volume":"103","author":"S D Patel","year":"2016","journal-title":"The British Journal of Surgery"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"e002938","DOI":"10.1161\/JAHA.115.002938","article-title":"Critical limb ischemia: Current trends and future directions","volume":"5","author":"M Teraa","year":"2016","journal-title":"Journal of the American Heart Association"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0140-6736(02)09670-8","article-title":"Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: A pilot study and a randomised controlled trial","volume":"360","author":"E Tateishi-Yuyama","year":"2002","journal-title":"Lancet (London, England)"},{"key":"ref7","first-page":"7528464","article-title":"Autologous stem cell therapy in critical limb ischemia: A meta-analysis of randomized controlled trials","volume":"2018","author":"B Xie","year":"2018","journal-title":"Stem Cells International"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3727\/096368916X692726","article-title":"Transplantation of human placenta-derived mesenchymal stem cells alleviates critical limb ischemia in diabetic nude rats","volume":"26","author":"L Liang","year":"2017","journal-title":"Cell Transplant"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"e9212","DOI":"10.1097\/MD.0000000000009212","article-title":"Three-week topical treatment with placenta-derived mesenchymal stem cells hydrogel in a patient with diabetic foot ulcer: A case report","volume":"96","author":"X Zeng","year":"2017","journal-title":"Medicine"},{"key":"ref10","first-page":"94","article-title":"Transplantation of placenta-derived mesenchymal stem cells in type 2","volume":"5","author":"R Jiang","year":"2011","journal-title":"diabetes: A pilot study. Frontiers of Medicine"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1111\/j.1365-2141.2008.07492.x","article-title":"Manufacturing of human placenta-derived mesenchymal stem cells for clinical trials","volume":"144","author":"G Brooke","year":"2009","journal-title":"British Journal of Haematology"},{"key":"ref12","first-page":"497","article-title":"Clinical evaluation of human umbilical cord mesenchymal stem cell transplantation after angioplasty for diabetic foot. 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angiogenesis in patients with severe limb ischemia by transplantation of a combination stem cell product","volume":"144","author":"G P Lasala","year":"2012","journal-title":"The Journal of Thoracic and Cardiovascular Surgery"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s00268-012-1892-6","article-title":"Intra-arterial allogeneic mesenchymal stem cells for critical limb ischemia are safe and efficacious: Report of a phase I study","volume":"37","author":"A K Das","year":"2013","journal-title":"World J Surg"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1253\/circj.CJ-11-1135","article-title":"Safety and effect of adipose tissue-derived stem cell implantation in patients with critical limb ischemia: A pilot study","volume":"76","author":"H C Lee","year":"2012","journal-title":"Circulation Journal: Official Journal of the Japanese Circulation Society"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s13287-017-0660-9","article-title":"Exosomes of human placenta-derived mesenchymal stem cells stimulate angiogenesis","volume":"8","author":"M Komaki","year":"2017","journal-title":"Stem Cell Res Ther"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/jcmm.12489","article-title":"Transplantation of placenta-derived mesenchymal stem cells enhances angiogenesis after ischemic limb injury in mice","volume":"20","author":"N Xie","year":"2016","journal-title":"Journal of Cellular and Molecular Medicine"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s10529-016-2067-6","article-title":"Hypoxia enhances the protective effects of placenta-derived mesenchymal stem cells against scar formation through hypoxia-inducible factor-1alpha","volume":"38","author":"L Du","year":"2016","journal-title":"Biotechnology Letters"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/scrt436","article-title":"Placental mesenchymal stem cells of fetal and maternal origins demonstrate different therapeutic potentials","volume":"5","author":"Y Zhu","year":"2014","journal-title":"Stem Cell Res Ther"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13287-016-0297-0","article-title":"VCAM-1+placenta chorionic villi-derived mesenchymal stem cells display potent pro-angiogenic activity","volume":"7","author":"W Du","year":"2016","journal-title":"Stem Cell Res Ther"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.bbrc.2013.07.088","article-title":"Placenta mesenchymal stem cell accelerates wound healing by enhancing angiogenesis in diabetic Goto-Kakizaki (GK) rats","volume":"438","author":"P Kong","year":"2013","journal-title":"Biochemical and Biophysical Research 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Immunology"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/sc.2013.132","article-title":"Expression of cytokines, growth factors and apoptosis-related signal molecules in chronic pressure ulcer wounds healing","volume":"52","author":"L Jiang","year":"2014","journal-title":"Spinal Cord"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13098-018-0343-4","article-title":"Adipose tissue-derived cytokines and their correlations with clinical characteristics in Vietnamese patients with type 2 diabetes mellitus","volume":"10","author":"N L Toan","year":"2018","journal-title":"Diabetology & Metabolic Syndrome"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/jdi.12579","article-title":"Adiponectin and pro-inflammatory cytokines are modulated in Vietnamese patients with type 2 diabetes mellitus","volume":"8","author":"H V Tong","year":"2017","journal-title":"Journal of Diabetes 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