Safety and Efficacy of Placenta-Derived Mesenchymal Stem Cell Treatment for Diabetic Patients with Critical Limb Ischemia: A Pilot Study

Abstract

Aim 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). Methods 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. Results 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. Conclusions 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.

Report of a phase 1 clinical trial for safety assessment of human placental mesenchymal stem cells therapy in patients with Critical limb ischemia (CLI)

“…Numerous clinical trials have demonstrated that cell-based therapies can help individuals with CLI. Only three phase I clinical studies that examined the tolerability and viability of P-MSCs for CLI have published the nal results from these trials (20,(39)(40)(41). However, no clinical research has documented the safety and effectiveness of utilizing P-MSCs to treat patients suffering from non-atherosclerotic PAD.…”

Topical and intravenous administration of human umbilical cord mesenchymal stem cells in patients with diabetic foot ulcer and peripheral arterial disease: a phase I pilot study with a 3-year follow-up

“…New collateral vessels were detected by CTA 1 month after hUC-MSC injection intramuscularly in a case series study [ 54 ], which indicated that angiostenosis was alleviated. Similarly, the symptoms of limb ischaemia were relieved after intramuscular injection of MSC, although no significant improvements in ABPI or revascularization were detected [ 59 ]. However, few improvements were observed in the ankle-brachial pressure index (ABPI) and ankle pressure after intramuscular injection of MSCs in a controlled study [ 20 ].…”

Phase 1 clinical trial for intravenous administration of mesenchymal stem cells derived from umbilical cord and placenta in patients with moderate COVID-19 virus pneumonia: Results of Stage 1 of the study

“…(22)(23)(24)(25)(26)(27)(28) Various clinical studies have demonstrated the safety and e cacy of umbilical cord and placental MSCs individually. (29)(30)(31)(32)(33)(34) For this study, a mixture of umbilical cord and placenta derived MSCs was used since, a mixture results in an enhanced outcome combining the bene ts of both types of cells. Invitro studies have shown that this mixture of cells secretes increased concentration of paracrine molecules such as IGF-1, KGF, VEGF, SDF-1α as compared to individual cell types which are responsible for stimulating lung repair, angiogenesis, stem cell recruitment, etc.…”