Epimorphic regeneration approach to tissue replacement in adult mammals
Epimorphic regeneration approach to tissue replacement in adult mammals
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DOI：
10.1073/pnas.0905851106
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发表时间：
2010-02-23
影响因子：
11.1
通讯作者：
Badylak, Stephen F.
中科院分区：
文献类型：
--
作者：
Agrawal, Vineet;Johnson, Scott A.;Badylak, Stephen F.
尾目动物和胚胎哺乳动物能够在各种组织中进行令人印象深刻的表型再生，而成年哺乳动物对损伤的典型默认反应包括炎症和疤痕组织形成。表型再生的一个组成部分是将常驻祖细胞和干细胞招募到损伤部位。细胞外基质(ECM)降解产生的生物活性分子在体外可在成年哺乳动物体内募集多种祖细胞和干细胞。在哺乳动物断指动物模型中，研究了体内应用趋化ECM降解产物将多潜能细胞募集到损伤部位的能力。成年、6-8周龄的C57/BL6小鼠接受右后脚第三指的第二节中段截肢，接受化学趋化性ECM降解产物治疗或不治疗。截肢后14天，接受ECM降解产物处理的小鼠显示出表达多能性标志的异质细胞的聚集，包括Sox2、Sca1和Rex1(Zfp42)。从截肢部位分离的细胞能够沿着神经外胚层和中胚层谱系分化，而从对照鼠分离的细胞只能沿着中胚层谱系分化。目前的发现表明，内源性干细胞被招募到损伤部位，和/或在那里产生/增殖，以响应细胞外基质降解产物。
Urodeles and fetal mammals are capable of impressive epimorphic regeneration in a variety of tissues, whereas the typical default response to injury in adult mammals consists of inflammation and scar tissue formation. One component of epimorphic regeneration is the recruitment of resident progenitor and stem cells to a site of injury. Bioactive molecules resulting from degradation of extracellular matrix (ECM) have been shown to recruit a variety of progenitor and stem cells in vitro in adult mammals. The ability to recruit multipotential cells to the site of injury by in vivo administration of chemotactic ECM degradation products in a mammalian model of digit amputation was investigated in the present study. Adult, 6- to 8-week-old C57/BL6 mice were subjected to midsecond phalanx amputation of the third digit of the right hind foot and either treated with chemotactic ECM degradation products or left untreated. At 14 days after amputation, mice treated with ECM degradation products showed an accumulation of heterogeneous cells that expressed markers of multipotency, including Sox2, Sca1, and Rex1 (Zfp42). Cells isolated from the site of amputation were capable of differentiation along neuroectodermal and mesodermal lineages, whereas cells isolated from control mice were capable of differentiation along only mesodermal lineages. The present findings demonstrate the recruitment of endogenous stem cells to a site of injury, and/or their generation/proliferation therein, in response to ECM degradation products.