Terminal differentiation is not a major determinant for the success of stem cell therapy - cross-talk between muscle-derived stem cells and host cells.
Terminal differentiation is not a major determinant for the success of stem cell therapy - cross-talk between muscle-derived stem cells and host cells.
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DOI：
10.1186/scrt72
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发表时间：
2011-07-08
影响因子：
7.5
通讯作者：
Huard J
中科院分区：
文献类型：
--
作者：
Gharaibeh B;Lavasani M;Cummins JH;Huard J
我们发现，当肌肉来源的干细胞（MDSCs）被植入多种组织时，只有一小部分供体细胞可以在再生组织中找到，绝大多数细胞是宿主来源的。其他研究人员使用多种不同类型的干细胞也记录了这一观察结果。据推测，移植干细胞通过动员宿主细胞并以旁分泌方式将其吸引到损伤部位，从而间接释放调节修复的因子。这个过程被粗略地称为“旁分泌机制”，但它的作用并不一定局限于损伤部位。为了支持这一推测，有报道称，增加血管生成导致心脏功能的改善，而抑制血管生成会降低受损血管化组织中干细胞的再生能力。这一观察结果支持了一项发现，即大多数参与修复过程的细胞确实被化学吸引到损伤部位，可能通过宿主新血管生成。由于最近观察到居住在血管壁内的细胞（内皮细胞和周细胞）似乎代表了出生后干细胞的起源，因此很容易假设通过新血管生成促进组织修复涉及这些血管来源的干细胞。对于非血管化组织，如关节软骨，注射干细胞的再生特性仍然促进旁分泌或旁观者效应，这涉及到在受损微环境中发现的驻留细胞，尽管不是通过促进血管生成。在本文中，我们回顾了目前对产后干细胞治疗的认识，并展示了植入干细胞对组织再生和修复过程的影响。我们认为移植干细胞的终末分化能力不是细胞再生潜能的主要决定因素，移植细胞赋予的旁分泌效应在再生过程中起着更大的作用。
We have found that when muscle-derived stem cells (MDSCs) are implanted into a variety of tissues only a small fraction of the donor cells can be found within the regenerated tissues and the vast majority of cells are host derived. This observation has also been documented by other investigators using a variety of different stem cell types. It is speculated that the transplanted stem cells release factors that modulate repair indirectly by mobilizing the host's cells and attracting them to the injury site in a paracrine manner. This process is loosely called a 'paracrine mechanism', but its effects are not necessarily restricted to the injury site. In support of this speculation, it has been reported that increasing angiogenesis leads to an improvement of cardiac function, while inhibiting angiogenesis reduces the regeneration capacity of the stem cells in the injured vascularized tissues. This observation supports the finding that most of the cells that contribute to the repair process are indeed chemo-attracted to the injury site, potentially through host neo-angiogenesis. Since it has recently been observed that cells residing within the walls of blood vessels (endothelial cells and pericytes) appear to represent an origin for post-natal stem cells, it is tempting to hypothesize that the promotion of tissue repair, via neo-angiogenesis, involves these blood vessel-derived stem cells. For non-vascularized tissues, such as articular cartilage, the regenerative property of the injected stem cells still promotes a paracrine, or bystander, effect, which involves the resident cells found within the injured microenvironment, albeit not through the promotion of angiogenesis. In this paper, we review the current knowledge of post-natal stem cell therapy and demonstrate the influence that implanted stem cells have on the tissue regeneration and repair process. We argue that the terminal differentiation capacity of implanted stem cells is not the major determinant of the cells regenerative potential and that the paracrine effect imparted by the transplanted cells plays a greater role in the regeneration process.
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影响因子：
19.6
作者：
Chen, Jun;Park, Hyeong-Cheon;Addabbo, Francesco;Ni, Jie;Pelger, Edward;Li, Houwei;Plotkin, Matthew;Goligorsky, Michael S.
通讯作者：
Goligorsky, Michael S.
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
DOI：
10.1302/0301-620x.85b2.13543
发表时间：
2003-03-01
影响因子：
--
作者：
Bentley, G;Biant, LC;Pringle, J
通讯作者：
Pringle, J
影响因子：
64.8
作者：
Conboy, IM;Conboy, MJ;Rando, TA
通讯作者：
Rando, TA
影响因子：
2.8
作者：
Day, CS;Kasemkijwattana, C;Huard, J
通讯作者：
Huard, J