未培养的微创处理脂肪来源干细胞可改善辐射性骨折愈合。
Noncultured Minimally Processed Adipose-Derived Stem Cells Improve Radiated Fracture Healing.
机构信息
From the Craniofacial Research Laboratory.
Orthopedic Research Laboratory, University of Michigan, Ann Arbor, MI.
出版信息
Ann Plast Surg. 2020 Jul;85(1):83-88. doi: 10.1097/SAP.0000000000002354.
Adipose-derived stem cells mitigate deleterious effects of radiation on bone and enhance radiated fracture healing by replacing damaged cells and stimulating angiogenesis. However, adipose-derived stem cell harvest and delivery techniques must be refined to comply with the US Food and Drug Administration restrictions on implantation of cultured cells into human subjects prior to clinical translation. The purpose of this study is to demonstrate the preservation of efficacy of adipose-derived stem cells to remediate the injurious effects of radiation on fracture healing utilizing a novel harvest and delivery technique that avoids the need for cell culture. Forty-four Lewis rats were divided into 4 groups: fracture control (Fx), radiated fracture control (XFx), radiated fracture treated with cultured adipose-derived stem cells (ASC), and radiated fracture treated with noncultured minimally processed adipose-derived stem cells (MP-ASC). Excluding the Fx group, all rats received a fractionated human-equivalent dose of radiation. All groups underwent mandibular osteotomy with external fixation. Following sacrifice on postoperative day 40, union rate, mineralization, and biomechanical strength were compared between groups at P < 0.05 significance. Compared with Fx controls, the XFx group demonstrated decreased union rate (100% vs 20%), bone volume fraction (P = 0.003), and ultimate load (P < 0.001). Compared with XFx controls, the MP-ASC group tripled the union rate (20% vs 60%) and demonstrated statistically significant increases in both bone volume fraction (P = 0.005) and ultimate load (P = 0.025). Compared with the MP-ASC group, the ASC group showed increased union rate (60% vs 100%) and no significant difference in bone volume fraction (P = 0.936) and ultimate load (P = 0.202). Noncultured minimally processed adipose-derived stem cells demonstrate the capacity to improve irradiated fracture healing without the need for cell proliferation in culture. Further refinement of the cell harvest and delivery techniques demonstrated in this report will enhance the ability of noncultured minimally processed adipose-derived stem cells to improve union rate and bone quality, thereby optimizing clinical translation.
脂肪来源干细胞通过替代受损细胞和刺激血管生成来减轻辐射对骨骼的有害影响并增强辐射性骨折愈合。但是，脂肪来源干细胞的采集和输送技术必须加以改进，以符合美国食品和药物管理局的规定，即在将培养的细胞植入人体进行临床转化之前，禁止植入。本研究的目的是利用一种新的采集和输送技术来证明脂肪来源干细胞的功效，该技术可避免细胞培养，从而减轻辐射对骨折愈合的损害。将 44 只 Lewis 大鼠分为 4 组：骨折对照组（Fx）、放射骨折对照组（XFx）、用培养的脂肪来源干细胞（ASC）治疗的放射骨折组和用非培养的最小处理的脂肪来源干细胞（MP-ASC）治疗的放射骨折组。除 Fx 组外，所有大鼠均接受了分次的人等效剂量的辐射。所有组均接受下颌骨切开术和外固定。术后第 40 天处死大鼠，比较各组之间的愈合率、矿化和生物力学强度（P < 0.05）。与 Fx 对照组相比，XFx 组的愈合率（100% vs 20%）、骨体积分数（P = 0.003）和极限载荷（P < 0.001）均降低。与 XFx 对照组相比，MP-ASC 组的愈合率提高了两倍（20% vs 60%），并且骨体积分数（P = 0.005）和极限载荷（P = 0.025）均有统计学显著增加。与 MP-ASC 组相比，ASC 组的愈合率更高（60% vs 100%），但骨体积分数（P = 0.936）和极限载荷（P = 0.202）无显著差异。未培养的最小处理的脂肪来源干细胞在无需细胞在培养中增殖的情况下，显示出改善辐射性骨折愈合的能力。本报告中展示的细胞采集和输送技术的进一步改进将增强未培养的最小处理的脂肪来源干细胞改善愈合率和骨质量的能力，从而优化临床转化。
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