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最近,美国德克萨斯大学(UT)西南医疗中心儿童研究所(CRI)已经确定了一种生物标志物,使研究人员能够准确地描述体内骨髓间充质干细胞(MSCs)的特性和功能。 $ n& \# H! A9 V) L7 \. E
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MSCs是美国国立卫生研究院注册的近200个临床试验的重点,这些试验涉及骨折,软骨损伤,椎间盘退行性疾病,骨关节炎等疾病。
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l6 ?* z+ W3 z间充质干细胞(mesenchymal stem cells,MSC),是一种具有自我复制能力和多向分化潜能的成体干细胞,这种干细胞能够发育成硬骨、软骨、脂肪和其他类型的细胞。间充质干细胞属于非终末分化细胞,它既有间质细胞,又有内皮细胞及上皮细胞的特征。不论是自体还是同种异源的间充质干细胞,一般都不会引起宿主的免疫反应。
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% |- D, ]- f* b# b由于间充质干细胞具备的这种免疫学特性,使其在自身免疫性疾病以及各种替代治疗等方面具有广阔的临床应用前景。通过自体移植可以重建组织器官的结构和功能,并且可避免免疫排斥反应。但一直以来,对MCSs的鉴定和生理功能研究,都由于缺乏生物标志物而受到阻碍。9 q* n1 b# F: `
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这一发现发表在Cell Stem Cell杂志上,显著推进MSC生物学研究,如果CRI确定在小鼠中确定的生物标志物在人类中也存在,将能够更好地识别和表征相关细胞,对于使用MSCs临床试验的前景。 l6 d1 G! G9 Y% z8 k8 r
. P' B( d9 [& {5 ^/ d, k% L- I* D4 C! V% i% |我们一直在MCSs临床关注的越来越多,但进展一直缓慢,因为研究人员迄今已无法辨认MSCs,研究其在身体内的正常生理功能。我们发现,被称为瘦蛋白受体的蛋白可以作为一种生物标记,准确地识别成人骨髓内MSCs,而且这些MSCs是新骨形成和骨修复损伤后的主要来源。9 {; K) f, K) ^) F) i. _
5 D1 }. x4 `! s0 N j在他们的研究过程中,研究人员发现瘦素受体阳性细胞也是促进骨髓中造血干细胞维持的因素的主要来源。不幸的是,许多临床试验正在测试使用MSCs疗法的潜力,已经被阻碍,利用的培养细胞缺乏特征和不纯。如果这一发现被复制在人类MSCs,可以增加利用MSCs精心设计临床试验的成功概率。+ d' F2 @- ?/ ]
# ^- s* D- X! l6 ~doi:10.1016/j.stem.2014.06.008/ x$ |. v5 Z6 i/ r* w
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- C5 X! F! w0 O8 ALeptin-Receptor-Expressing Mesenchymal Stromal Cells Represent the Main Source of Bone Formed by Adult Bone Marrow% s+ c( W0 Y* T. ~5 w& `
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9 o1 S' m9 L) ^8 JBo O. Zhou, Rui Yue, Malea M. Murphy, James G. Peyer, Sean J. Morrison
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Summary: Studies of the identity and physiological function of mesenchymal stromal cells (MSCs) have been hampered by a lack of markers that permit both prospective identification and fate mapping in vivo. We found that Leptin Receptor (LepR) is a marker that highly enriches bone marrow MSCs. Approximately 0.3% of bone marrow cells were LepR+, 10% of which were CFU-Fs, accounting for 94% of bone marrow CFU-Fs. LepR+ cells formed bone, cartilage, and adipocytes in culture and upon transplantation in vivo. LepR+ cells were Scf-GFP+, Cxcl12-DsRedhigh, and Nestin-GFPlow, markers which also highly enriched CFU-Fs, but negative for Nestin-CreER and NG2-CreER, markers which were unlikely to be found in CFU-Fs. Fate-mapping showed that LepR+ cells arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture. LepR+ cells were quiescent, but they proliferated after injury. Therefore, LepR+ cells are the major source of bone and adipocytes in adult bone marrow.
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