骨髓间充质干细胞复合多肽凝胶及成软骨生成因子修复兔关节软骨缺损

背景：多肽水凝胶因为其具有良好的可塑型性，能够与损伤部位很好的无缝隙结合，所以采用该材料作为支架是骨、软骨组织工程中一种可行的探索。 目的：骨髓间充质干细胞联合新型可注射多肽凝胶及成软骨生成因子修复兔关节软骨缺损，观察其修复效果。 方法：首先分离培养兔骨髓间充质干细胞，兔左侧膝关节处制备直径5 mm，深3 mm的全层骨-软骨缺损模型；右侧造模后空置作为对照。实验分为3组，单纯自组装多肽凝胶移植组，自组装多肽凝胶+成软骨因子组和自组装多肽凝胶+成软骨因子+骨髓间充质干细胞组。采用的成软骨因子包括转化生长因子β1，地塞米松和胰岛素样生长因子1，三者混合后加入到自组装多肽凝胶或骨髓间充质干细胞中。于处理后12周时处死动物行大体及组织学观察、X射线摄片、免疫组织化学法进行组织学评分评估修复情况。 结果与结论：单纯自组装多肽凝胶移植在12周后显示出非常好的修复效果，可见番红O染色，Ⅱ型胶原蛋白免疫组织化学染色强度以及组织学评分明显高于其他组(P < 0.05)。自组装多肽凝胶+成软骨因子组修复效果较好，与自组装多肽凝胶组相似，但其修复区域蛋白聚糖表达比对照组明显升高(P < 0.01)。自组装多肽凝胶+成软骨因子+骨髓间充质干细胞组修复效果不佳，12周未能完全修复缺损区域，与单纯自组装多肽凝胶组比较骨赘的形成有所增加。结果表明，单纯自组装多肽凝胶能够在原位修复骨软骨缺损并促进软骨修复，提示以自组装多肽凝胶支架移植有望提高目前修复软骨缺损的效果。中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程全文链接：

Bone marrow mesenchymal stem cells combined with peptide hydrogel and chondrogenic factors for repair of articular cartilage defects in rabbits

BACKGROUND:Peptide hydrogel has good plasticity, and it can fill the injured site very well; therefore, to use this material as a scaffold is a feasible exploration in bone and cartilage tissue engineering. OBJECTIVE:To test the effect of bone marrow mesenchymal stem cells combined with injectable peptide hydrogel and chondrogenic factors for repair of articular cartilage defects in rabbits. METHODS:Bone marrow mesenchymal stem cells from rabbits were isolated and cultured. A full-thickness bone-cartilage defect model, 5 mm in diameter and 3 mm in depth, was made on the left knee joint of rabbits, and the right knee joint of rabbits with no treatment was used as control after modeling. There were three experimental groups: self-assembling peptide hydrogel group, peptide hydrogel+chondrogenic factors group, and peptide hydrogel+chondrogenic factors+bone marrow mesenchymal stem cells group. Transforming growth factor β1, dexamethasone and insulin-like growth factor 1 were mixed as chondrogenic factors and added into self-assembling peptide hydrogel or bone marrow mesenchymal stem cells. Twelve weeks after treatment, animals were sacrificed for gross and histological observation, X-ray radiography, and histological evaluation using immunohistochemistry method. RESULTS AND CONCLUSION:At 12 weeks after treatment, the self-assembling peptide hydrogel group showed excellent results in the cartilage repair, and better achievements in safranin-O staining, collagen II immunostaining, and histological scores than the other groups (P < 0.05); the peptide hydrogel+chondrogenic factors group had better repair effects similar to the self-assembling peptide hydrogel group, but the expression of proteoglycans was higher than that in the control group (P < 0.01); there were poorer repair effects and more osteophytes in the peptide hydrogel+chondrogenic factors+bone marrow mesenchymal stem cells group than the the peptide hydrogel+ chondrogenic factors group. Experimental findings indicate that the self-assembling peptide hydrogel can repair cartilage defects in situ and improve cartilage repair, which is expected to improve current repairing effects on cartilage defects.