Zhang Weixin, Zheng Cheng, Yu Tiefeng, Zhang Houjian, Huang Jiaxin, Chen Liyue, Tong Peijian, Zhen Gehua
Department of Traditional Chinese Medical Orthopedic Surgery, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Orthopedic Surgery, School of Medicine, Johns Hopkins University, Baltimore, MD, United States.
Front Cell Dev Biol. 2022 Oct 18;10:1014789. doi: 10.3389/fcell.2022.1014789. eCollection 2022.
Femoral head necrosis (FHN), one of the most popular joint diseases in the musculoskeletal system, is usually attributed to local ischemia of the femoral head. Thus, regenerating the vascularization capacity and restoring the local perfusion of the femoral head becomes an efficient therapeutic approach for FHN. We investigated the function of autologous lipoaspirate cells (LPCs) in regenerating circulation in FHN animal models and human subjects in this study. We also explored the mechanisms of why LPCs show a superior effect than that of the bone marrow-derived stem cells (BMSCs) in vascularization. Thirty-four FHN patients were recruited for the randomized clinical trial. Harris Hip Score (HHS) and digital subtraction arteriography (DSA) and interventional technique were used to compare the efficacy of LPCs treatment and vehicle therapy in improving femoral head circulation and hip joint function. Cellular mechanism that underlies the beneficial effect of LPCs in restoring blood supply and rescuing bone architecture was further explored using canine and mouse FHN animal models. We found that LPCs perfusion through the medial circumflex artery will promote the femoral head vascularization and bone structure significantly in both FHN patients and animal models. The HHS in LPCs treated patients was significantly improved relative to vehicle group. The levels of angiogenesis factor secreted by LPCs such as VEGF, FGF2, VEC, TGF-β, were significantly higher than that of BMSCs. As the result, LPCs showed a better effect in promoting the tube structure formation of human vascular endothelial cells (HUVEC) than that of BMSCs. Moreover, LPCs contains a unique CD44CD34CD31 population. The CD44CD34CD31 LPCs showed significantly higher angiogenesis potential as compared to that of BMSCs. Taken together, our results show that LPCs possess a superior vascularization capacity in both autonomous and paracrine manner, indicating that autologous LPCs perfusion the medial circumflex artery is an effective therapy for FHN.
股骨头坏死(FHN)是肌肉骨骼系统中最常见的关节疾病之一,通常归因于股骨头局部缺血。因此,恢复股骨头的血管生成能力并恢复其局部灌注成为治疗FHN的有效方法。在本研究中,我们调查了自体脂肪抽吸细胞(LPCs)在FHN动物模型和人类受试者中再生循环的功能。我们还探讨了LPCs在血管生成方面比骨髓来源的干细胞(BMSCs)表现出更优效果的机制。34名FHN患者被纳入随机临床试验。使用Harris髋关节评分(HHS)、数字减影血管造影(DSA)和介入技术来比较LPCs治疗和空白对照治疗在改善股骨头循环和髋关节功能方面的疗效。使用犬和小鼠FHN动物模型进一步探索了LPCs在恢复血液供应和挽救骨骼结构方面产生有益作用的细胞机制。我们发现,通过旋股内侧动脉灌注LPCs在FHN患者和动物模型中均能显著促进股骨头血管生成和骨结构。与空白对照组相比,接受LPCs治疗的患者的HHS显著改善。LPCs分泌的血管生成因子如VEGF、FGF2、VEC、TGF-β的水平显著高于BMSCs。结果,LPCs在促进人血管内皮细胞(HUVEC)形成管状结构方面比BMSCs表现出更好的效果。此外,LPCs包含独特的CD44CD34CD31细胞群。与BMSCs相比,CD44CD34CD31 LPCs表现出显著更高的血管生成潜力。综上所述,我们的结果表明,LPCs以自主和旁分泌方式均具有卓越的血管生成能力,表明通过旋股内侧动脉灌注自体LPCs是治疗FHN的有效方法。