Establishing reliable criteria for isolating myogenic cell fractions with stem cell properties and enhanced regenerative capacity
Establishing reliable criteria for isolating myogenic cell fractions with stem cell properties and enhanced regenerative capacity
复制标题
DOI：
10.1016/j.bcmd.2003.09.012
复制
发表时间：
2004-01-01
影响因子：
2.3
通讯作者：
Huard, J
中科院分区：
文献类型：
--
作者：
Jankowski, RJ;Huard, J
尽管在肌源性细胞移植领域进行了集中的努力，但在可靠地鉴定和分离能够耐受移植后初始环境并有效再生临床相关数量的肌肉的祖细胞方面进展甚微。肌源性治疗模式的未来成功需要更好地理解肌源性前体细胞池的高度异质性，这已经被许多研究人员所证实。此外，为了将实验动物的结果转化为临床应用，必须建立可靠的体外选择标准，并且必须可以跨物种翻译。虽然对表面标记的效用的研究仍在进行中，但作为替代方案，我们已经研究了在强加条件下的细胞行为特征，这些条件挑战了成肌祖细胞在不同细胞命运之间进行选择的倾向(即，增殖、静止或分化)。先前在小鼠中的观察表明，肌源性群体的体内再生能力增强，因为他们在体外保持增殖和未分化状态的能力[J.细胞科学]。115(2002)4361]。因此，从这些观察中可以推测，这种行为可能是移植后再生能力的先验指标。为了挑战这一命题，以相同的方式对大鼠细胞分离和移植模型进行了评估。与从小鼠身上获得的结果一致，再生能力和分化诱导之间存在显著的相关性。这些结果有助于越来越多的科学证据记录不同肌源性祖细胞之间存在的潜在行为差异，同时重要的是，也提供了证据表明这些差异可能显著影响这些细胞在移植后的功能能力。这一信息进一步表明，从治疗的角度来看，旨在获得高效肌源性祖细胞的分离策略应该在缺乏可靠的表面标记(S)的情况下，专注于鉴定在体外表现出良好行为(即高增殖能力和低诱导分化)的群体。将这些标准结合到细胞分离和/或纯化方案中，可能会在临床肌源性移植环境中产生显著的回报。(C)2003 Elsevier Inc.保留所有权利。
Despite a focused effort within the myogenic cell transplantation community, little progress has been made toward the reliable identification and isolation of progenitors that are capable of tolerating the initial posttransplantation environment and effectively regenerating clinically relevant quantities of muscle. The future success of myogenic-based treatment modalities requires an enhanced understanding of the highly heterogeneous nature of the myogenic progenitor cell pool, which has been previously documented by numerous researchers. Further, for translation of experimental animal results to clinical application, reliable in vitro selection criteria must be established and must be translatable across species. While research into the utility of surface markers is ongoing, as an alternative we have investigated in vitro cell behavioral characteristics under imposed conditions which challenge the propensity of myogenic progenitors to choose between various cell fates (i.e., proliferation, quiescence, or differentiation). Previous observations in the mouse suggest an enhanced in vivo regenerative capacity of myogenic populations with respect to their in vitro ability to maintain a proliferative and undifferentiated state [J. Cell Sci. 115 (2002) 4361]. From these observations it is thus proposed that such behavior may represent an a priori indicator of regenerative capacity following transplantation. To challenge this proposition, a rat cell isolation and transplantation model was evaluated in an identical manner. In agreement with the results obtained from the mouse, a significant correlation between regenerative capacity and induction of differentiation was observed. These results contribute to the growing body of scientific evidence documenting the underlying behavioral differences that exist between various myogenic progenitors while also, importantly, providing evidence that such differences may significantly impact the functional capabilities of these cells posttransplantation. This information further implies that from a therapeutic standpoint isolation strategies aimed toward obtaining efficient myogenic progenitors should, in the absence of a reliable surface marker(s), focus on identifying populations displaying desirable in vitro behavior (i.e., high proliferative capacity and low induced differentiation). Incorporating such criteria into cell isolation and/or purification schemes may yield significant returns in the clinical myogenic transplantation setting. (C) 2003 Elsevier Inc. All rights reserved.