Lancet:首次成功利用兔子自身干细胞再生关节

2010-08-03 文章来源:骨科在线 点击量:1712   我要说

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7月29日,著名学术杂志《柳叶刀》(The Lancet)在线发布了一美籍华裔科学家首次成功利用干细胞培植出骨骼和软骨组织,填补残缺的腿关节。据香港《文汇报》报道称,再生关节完全在动物体内培植,是该实验的另一大突破,为日后病人在自己体内利用自身干细胞培植髋关节和膝关节奠下基础。
美国哥伦比亚大学医学中心的华裔科学家Jeremy J.Mao领导的研究小组在此次研究中,先移除了10只兔子的大腿关节,再在相关部位植入一种已注入生长激素的人造支架。生长激素会刺激干细胞生长,并引导干细胞移向失去关节的部位,分两层再生骨骼和软骨。在4周内,兔子就可如常活动。之前,即年内5月25日,Jeremy J.Mao领导的研究小组宣布牙齿再生技术获得新突破,研究人员成功在动物口腔内进行了牙齿再生实验,这意味着未来人们就可将该技术应用于临床实验领域。新的技术只需在患者口腔内植入一个托架,并将患者体内的干细胞引导至需要牙齿再生的地方,就可以实现真正意义上的“牙齿再生”。

相关内容:J.Dental Research:人体干细胞成功造出人工牙齿

目前要把这科技应用在人类身上尚困难重重。由于人类用双腿来负重,髋关节的再生过程会更漫长;若本身患有某些疾病或正接受药物疗程,或会对骨骼再生带来不良影响;长者或糖尿病患者亦缺乏正常的再生能力。有专家预计,距技术发展成熟还需20至30年。
杰里米·毛对新发现最终可造福人类,再生膝、肩、髋和手指关节和骨骼充满信心。再生关节可发挥原本关节的运动、负重等作用,而且比现有的人造组织更耐用,从而解决病人换上金属代用关节后,还需在15至20年内再进行更换手术的烦恼。

原文出处:
The Lancet, doi:10.1016/S0140-6736(10)60668-X
Regeneration of the articular surface of the rabbit synovial joint by cell
homing: a proof of concept study
Chang H Lee PhD a, James L Cook DVM b, Avital Mendelson MS a, Eduardo K Moioli
PhD a, Hai Yao PhD c, Prof Jeremy J Mao PhD a
Background
A common approach for tissue regeneration is cell delivery, for example by direct transplantation of stem or progenitor cells. An alternative, by recruitment of endogenous cells, needs experimental evidence. We tested the hypothesis that the articular surface of the synovial joint can regenerate with a biological cue spatially embedded in an anatomically correct bioscaffold.
Methods
In this proof of concept study, the surface morphology of a rabbit proximal humeral joint was captured with laser scanning and reconstructed by computer-aided design. We fabricated an anatomically correct bioscaffold using a composite of poly-?-caprolactone and hydroxyapatite. The entire articular surface of unilateral proximal humeral condyles of skeletally mature rabbits was surgically excised and replaced with bioscaffolds spatially infused with transforming growth factor β3 (TGFβ3)-adsorbed or TGFβ3-free collagen hydrogel. Locomotion and weightbearing were assessed 1—2, 3—4, and 5—8 weeks after surgery. At 4 months, regenerated cartilage samples were retrieved from in vivo and assessed for surface fissure, thickness, density, chondrocyte numbers, collagen type II and aggrecan, and mechanical properties.
Findings
Ten rabbits received TGFβ3-infused bioscaffolds, ten received TGFβ3-free bioscaffolds, and three rabbits underwent humeral-head excision without bioscaffold replacement. All animals in the TGFβ3-delivery group fully resumed weightbearing and locomotion 3—4 weeks after surgery, more consistently than those in the TGFβ3-free group. Defect-only rabbits limped at all times. 4 months after surgery, TGFβ3-infused bioscaffolds were fully covered with hyaline cartilage in the articular surface. TGFβ3-free bioscaffolds had only isolated cartilage formation, and no cartilage formation occurred in defect-only rabbits.
TGFβ3 delivery yielded uniformly distributed chondrocytes in a matrix with collagen type II and aggrecan and had significantly greater thickness (p=0·044) and density (p<0·0001) than did cartilage formed without TGFβ3. Compressive and shear properties of TGFβ3-mediated articular cartilage did not differ from those of native articular cartilage, and were significantly greater than those o

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