Abstract
INTRODUCTION: The prevalence of diabetes mellitus is increasing globally, including in Japan. Patients with diabetes often experience microangiopathy and macroangiopathy, which lead to difficult-to-treat foot ulcers and diabetic gangrene. Conventional cellular therapies have limited safety and are invasive. In this study, we investigated the use of cultured autologous mesenchymal stromal cells derived from the bone marrow and grown in platelet-rich plasma as a potential treatment for diabetic complications. METHODS: A prospective clinical trial was conducted to assess safety as the primary endpoint and efficacy as the secondary endpoint of the aforementioned therapy in five patients with critical limb ischemia, with or without hemodialysis. RESULTS: Five patients with critical limb ischemia were enrolled between 2016 and 2019, three of whom underwent hemodialysis. Platelet-rich plasma was obtained from 288 ± 39.6 mL of blood/patient, yielding 31.6 ± 1.67 mL of platelet-rich plasma. Bone marrow aspiration yielded 18.4 ± 4.77 mL/patient, and 4.64 ± 1.51 × 10(7) cells were incubated for 16 ± 2.8 days to obtain 3.26 ± 0.33 × 10(7) mesenchymal stromal cells. Although several adverse events were observed, none were directly attributed to cell therapy. Clinical severity, as assessed by both the Fontaine stage and Rutherford category, improved significantly following therapy. This improvement was accompanied by enhancements in the 6-min walking distance, dorsal skin perfusion pressure, ankle transcutaneous partial oxygen pressure, and ankle brachial pressure index. CONCLUSION: Autologous angiogenic therapy with cultured mesenchymal stromal cells derived from the bone marrow and grown in platelet-rich plasma is a safe and feasible, and was expected as a potential treatment for critical limb ischemia.