Partial Characterization of the Sox2+Cell Population in an Adult Murine Model of Digit Amputation
Partial Characterization of the Sox2+Cell Population in an Adult Murine Model of Digit Amputation
复制标题
DOI：
10.1089/ten.tea.2011.0550
复制
发表时间：
2012-07-01
影响因子：
4.1
通讯作者：
Badylak, Stephen F.
中科院分区：
文献类型：
--
作者：
Agrawal, Vineet;Siu, Bernard F.;Badylak, Stephen F.
成年哺乳动物响应损伤的组织再生通常仅限于选定的组织。蝾螈和蝾螈等非哺乳动物物种通过招募和积累经过预先编程以重现缺失组织的局部和循环多能祖细胞来实现四肢和手指等复杂组织的再生。在成年哺乳动物损伤部位定向募集和激活祖细胞可能会改变从疤痕组织到再生的默认伤口愈合反应。细胞外基质 (ECM) 蛋白的蛋白水解降解产生的生物活性分子已被证明可以在体外和体内将多种祖细胞募集到损伤部位。本研究进一步描述了在成熟的小鼠手指截肢模型中用 ECM 降解产物治疗后在损伤部位积累的细胞群的特征。对 6-8 周大的成年小鼠进行第二节指骨中指截肢后，用 ECM 降解产物进行治疗导致异质细胞群的积累，其中一部分表达转录因子 Sox2，这是多能和成年祖细胞的标志物。 Sox2+ 细胞位于截肢 P2 骨的侧面，共表达祖细胞标记物 CD90 和 Sca1。转基因Sox2 eGFP/+和骨髓嵌合小鼠表明，骨髓和血液循环对Sox2+细胞群没有贡献。目前的研究表明，除了循环祖细胞外，在用 ECM 降解产物治疗后，常驻组织衍生细胞也会在损伤部位增殖。尽管未来的工作有必要确定 Sox2+ 细胞对损伤部位功能组织的贡献，但局部组织衍生细胞的募集和/或激活可能是成年哺乳动物中更复杂组织的组织工程的可行方法。
Tissue regeneration in response to injury in adult mammals is generally limited to select tissues. Nonmammalian species such as newts and axolotls undergo regeneration of complex tissues such as limbs and digits via recruitment and accumulation of local and circulating multipotent progenitors preprogrammed to recapitulate the missing tissue. Directed recruitment and activation of progenitor cells at a site of injury in adult mammals may alter the default wound-healing response from scar tissue toward regeneration. Bioactive molecules derived from proteolytic degradation of extracellular matrix (ECM) proteins have been shown to recruit a variety of progenitor cells in vitro and in vivo to the site of injury. The present study further characterized the population of cells accumulating at the site of injury after treatment with ECM degradation products in a well-established model of murine digit amputation. After a mid-second phalanx digit amputation in 6-8-week-old adult mice, treatment with ECM degradation products resulted in the accumulation of a heterogeneous population of cells, a subset of which expressed the transcription factor Sox2, a marker of pluripotent and adult progenitor cells. Sox2+ cells were localized lateral to the amputated P2 bone and coexpressed progenitor cell markers CD90 and Sca1. Transgenic Sox2 eGFP/+ and bone marrow chimeric mice showed that the bone marrow and blood circulation did not contribute to the Sox2+ cell population. The present study showed that, in addition to circulating progenitor cells, resident tissue-derived cells also populate at the site of injury after treatment with ECM degradation products. Although future work is necessary to determine the contribution of Sox2+ cells to functional tissue at the site of injury, recruitment and/or activation of local tissue-derived cells may be a viable approach to tissue engineering of more complex tissues in adult mammals.