Recruitment of Progenitor Cells by an Extracellular Matrix Cryptic Peptide in a Mouse Model of Digit Amputation
Recruitment of Progenitor Cells by an Extracellular Matrix Cryptic Peptide in a Mouse Model of Digit Amputation
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DOI：
10.1089/ten.tea.2011.0036
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发表时间：
2011-10-01
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;Tottey, Stephen;Badylak, Stephen F.
由细胞外基质（ECM）组成的生物支架已成功地用于临床前模型和人类损伤后功能性、部位适当组织的建设性重塑。ECM介导的建设性重塑的机制尚未完全了解，但支架降解和定向募集的分化和祖细胞被认为发挥关键作用。先前的研究表明，ECM支架的降解产物可以在体外和体内招募祖细胞群体。本研究确定了一个单一的隐蔽肽衍生自胶原蛋白III分子的a亚基，是一个良好的特征血管周围干细胞在体外趋化，并导致祖细胞在体内的定点积累。该寡肽在体外对人皮质神经干细胞、大鼠脂肪干细胞、C2 C12成肌细胞和大鼠雪旺细胞具有额外的趋化性。在成年鼠模型的手指截肢，治疗后，这种肽中第二节趾骨截肢导致更多的Sox 2+和Sca 1+，Lin-细胞在损伤部位相比，控制。由于祖细胞活化和募集是成年哺乳动物组织中表型再生的关键先决条件，因此这些细胞的内源性定点募集具有改变从瘢痕组织朝向再生的默认伤口愈合反应的潜力。
Biologic scaffolds composed of extracellular matrix (ECM) have been used successfully in preclinical models and humans for constructive remodeling of functional, site-appropriate tissue after injury. The mechanisms underlying ECM-mediated constructive remodeling are not completely understood, but scaffold degradation and site-directed recruitment of both differentiated and progenitor cells are thought to play critical roles. Previous studies have shown that degradation products of ECM scaffolds can recruit a population of progenitor cells both in vitro and in vivo. The present study identified a single cryptic peptide derived from the a subunit of the collagen III molecule that is chemotactic for a well-characterized perivascular stem cell in vitro and causes the site-directed accumulation of progenitor cells in vivo. The oligopeptide was additionally chemotactic for human cortical neural stem cells, rat adipocyte stem cells, C2C12 myoblast cells, and rat Schwann cells in vitro. In an adult murine model of digit amputation, treatment with this peptide after mid-second phalanx amputation resulted in a greater number of Sox2 + and Sca1 +, Lin- cells at the site of injury compared to controls. Since progenitor cell activation and recruitment are key prerequisites for epimorphic regeneration in adult mammalian tissues, endogenous site-directed recruitment of such cells has the potential to alter the default wound healing response from scar tissue toward regeneration.