Fukuda Shoji, Hagiwara Shotaro, Okochi Hitoshi, Ishiura Nobuko, Nishibe Toshiya, Yakabe Ryo, Suzuki Hiroko
Department of Cardiovascular Surgery, Tokyo Medical University, Tokyo, Japan.
Department of Hematology, Tsukuba University Hospital Mito Clinical Education and Training Center, Ibaragi, Japan.
Regen Ther. 2023 Sep 21;24:472-478. doi: 10.1016/j.reth.2023.09.011. eCollection 2023 Dec.
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.
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.
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 cells were incubated for 16 ± 2.8 days to obtain 3.26 ± 0.33 × 10 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.
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.
全球糖尿病患病率呈上升趋势，日本也不例外。糖尿病患者常出现微血管病变和大血管病变，进而导致难以治疗的足部溃疡和糖尿病坏疽。传统的细胞疗法安全性有限且具有侵入性。在本研究中，我们调查了使用从骨髓中提取并在富含血小板血浆中培养的自体间充质基质细胞作为糖尿病并发症潜在治疗方法的情况。
进行了一项前瞻性临床试验，以安全性作为主要终点，疗效作为上述疗法在五名伴有或不伴有血液透析的严重肢体缺血患者中的次要终点进行评估。
2016年至2019年间纳入了五名严重肢体缺血患者，其中三名接受了血液透析。每位患者从288±39.6mL血液中获取富含血小板血浆，得到31.6±1.67mL富含血小板血浆。骨髓穿刺每位患者获取18.4±4.77mL，将4.64±1.51×10个细胞培养16±2.8天以获得3.26±0.33×10个间充质基质细胞。尽管观察到了一些不良事件，但均未直接归因于细胞治疗。治疗后，通过Fontaine分期和Rutherford分级评估的临床严重程度均有显著改善。这种改善伴随着6分钟步行距离、背部皮肤灌注压、踝部经皮局部氧分压和踝肱压力指数的提高。
用从骨髓中提取并在富含血小板血浆中培养的间充质基质细胞进行自体血管生成治疗是安全可行的，有望成为严重肢体缺血的一种潜在治疗方法。
