Stem Cells Transl Med：骨祖细胞已成功进行软骨修复

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来源：生物谷 2015-03-05 17:31
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1 n7 x( b7 b( B9 U) p: k4 ~2015年3月5日 讯 /生物谷BIOON/ --日前，来自曼彻斯特大学等处的研究人员利用人类胚胎干细胞成功制造产生了软骨组织，其或许在未来可以帮助治疗骨关节炎患者的关节疼痛等疾病，相关研究刊登于国际杂志Stem Cells Translational Medicine上。, ]$ ^7 b+ G' f9 Y. B

) }( d' T* y. w8 [研究者Kimber表示，这项研究为利用胚胎干细胞产生新型组织来用于治疗软骨损伤迈出了重要的一步，在研究中我们分析了胚胎干细胞分化成为前体软骨细胞的能力，随后我们将其植入了膝关节软骨缺失的大鼠体内，四周后大鼠机体的软骨得到了部分修复，12周后软骨上出现了光滑的表面，就如同正常的软骨组织一样，对新生成的软骨组织的深入研究后发现从胚胎干细胞分化生成的软骨细胞或许会在软骨组织中持续存在保持活性。0 J- `! P& T, ?* t' f5 `( K7 J

7 I1 b! _0 _3 h开发并且检测上述在大鼠体内移植胚胎干细胞的步骤或许可以帮助开发治疗关节炎患者的相应疗法，而研究者希望这种移植过程不仅可以产生新型健康的软骨组织，而且更重要的是不带来任何副作用，比如生长异常、组织紊乱或肿瘤生成等。来自成体干细胞生成的软骨细胞当前正在进行实验性应用，但由于其并不能实现大量生产因此诱导分化的操作程序就相应地变得昂贵起来。3 C8 @0 H/ f6 H0 h
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由于胚胎干细胞具有特殊的增殖能力，其可以被通过诱导分化成为任何成熟的细胞，从而就有可能实现大量软骨细胞的产生，目前研究者开发的新型生产过程具有强大的潜力生产大量的软骨细胞以供临床使用。骨关节炎在英国影响着800多万人的健康，其是致残的主要原因，当个体软骨的末端不断磨损引发关节疼痛及变得僵硬时骨关节炎就发生了。% @$ t/ f; }# N1 p% F$ c
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最后研究者Stephen Simpson说道，当前治疗骨关节炎的疗法由于并不能有效释放个体的疼痛感，而且其也并不是有效减缓逆转个体软骨退化的有效疗法；关节移植可以有效适用于老年人但却并不适用于年轻人或者那些经历运动损伤的运动员。本文研究中研究者揭示，胚胎干细胞或许可以作为软骨细胞产生的来源，来帮助有效治疗患骨关节炎的患者
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+ o6 l( V6 O5 C$ Ldoi:10.5966/sctm.2014-0101
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- T! T( q* E! ^& RCartilage Repair Using Human Embryonic Stem Cell-Derived Chondroprogenitors
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Aixin Chenga, Zoher Kapaceea,*, Jiang Pengb,*, Shibi Lub, Robert J. Lucasa, Timothy E. Hardinghama,c and Susan J. Kimbera' P" g$ {1 p( O, h
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In initial work, we developed a 14-day culture protocol under potential GMP, chemically defined conditions to generate chondroprogenitors from human embryonic stem cells (hESCs). The present study was undertaken to investigate the cartilage repair capacity of these cells. The chondrogenic protocol was optimized and validated with gene expression profiling. The protocol was also applied successfully to two lines of induced pluripotent stem cells (iPSCs). Chondrogenic cells derived from hESCs were encapsulated in fibrin gel and implanted in osteochondral defects in the patella groove of nude rats, and cartilage repair was evaluated by histomorphology and immunocytochemistry. Genes associated with chondrogenesis were upregulated during the protocol, and pluripotency-related genes were downregulated. Aggregation of chondrogenic cells was accompanied by high expression of SOX9 and strong staining with Safranin O. Culture with PluriSln1 was lethal for hESCs but was tolerated by hESC chondrogenic cells, and no OCT4-positive cells were detected in hESC chondrogenic cells. iPSCs were also shown to generate chondroprogenitors in this protocol. Repaired tissue in the defect area implanted with hESC-derived chondrogenic cells was stained for collagen II with little collagen I, but negligible collagen II was observed in the fibrin-only controls. Viable human cells were detected in the repair tissue at 12 weeks. The results show that chondrogenic cells derived from hESCs, using a chemically defined culture system, when implanted in focal defects were able to promote cartilage repair. This is a first step in evaluating these cells for clinical application for the treatment of cartilage lesions.
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