Do mesenchymal stem cells function across species barriers? Relevance for xenotransplantation.
Do mesenchymal stem cells function across species barriers? Relevance for xenotransplantation.
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DOI：
10.1111/xen.12000
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发表时间：
2012-09
影响因子：
3.9
通讯作者：
Cooper DK
中科院分区：
文献类型：
--
作者：
Li J;Ezzelarab MB;Cooper DK
同种异体间充质干（基质）细胞（MSC）是一种有前途的治疗各种病理条件。已证明转基因猪MSC在体外下调人T细胞对猪抗原的应答。然而，在转基因猪MSC可以用于临床之前，需要提供证据来表明它们是否能在人类（异种）宿主中存活。截至2011年底的文献检索确定了94份在各种实验模型中体内跨物种施用MSC的报告。大多数（n=89）涉及在各种其他物种中使用人MSC，偶尔使用猪，大鼠或豚鼠MSC进行研究。当使用人MSC时，它们主要来源于骨髓、脂肪组织或脐带血。给药途径多种多样，但几乎一半的研究采用静脉途径。在88个实验中（93.6%），有证据表明MSC植入并跨越物种屏障发挥作用，只有6例（6.4%）有证据表明功能失败。重要的是，MSC功能在几种不同的跨物种模型中得到证实。例如，人类MSC在不少于7种不同的受体物种中发挥作用。该文献检索提供的数据加强了猪MSC在不同物种中的功能令人满意的假设，例如，人类这些数据还表明，我们自己在体外观察到的猪MSC下调人T细胞对猪抗原的反应强度的功效，可能会在临床前大型动物模型和临床试验中重现。
Allogeneic mesenchymal stem (stromal) cells (MSC) are a promising therapy for various pathological conditions. Genetically-modified pig MSC have been demonstrated to downregulate the human T cell response to pig antigens in vitro. Before genetically-modified pig MSC can be used clinically, however, evidence needs to be provided to indicate whether they will survive in a human (xenogeneic) host. A literature search through the end of 2011 identified 94 reports of the in vivo cross-species administration of MSC in a variety of experimental models. The majority (n=89) involved the use of human MSC in various other species, with an occasional study using pig, rat, or guinea pig MSC. When human MSC were used, they were largely derived from the bone marrow, adipose tissue, or umbilical cord blood. The routes of administration were varied, though almost half of the studies utilized the intravenous route. In 88 experiments (93.6%) there was evidence that the MSC engrafted and functioned across the species barrier, and in only 6 cases (6.4%) was there evidence of failure to function. Importantly, MSC function was confirmed in several different cross-species models. For example, human MSC functioned in no fewer than 7 different recipient species. The data provided by this literature search strengthen the hypothesis that pig MSC will function satisfactorily in a different species, e.g., humans. The data also suggest that our own in vitro observations on the efficacy of pig MSC in downregulating the strength of the human T cell response to pig antigens will likely be reproduced in vivo in preclinical large animal models and in clinical trials.
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