Transplantation of Enteric Cells Expressing p75 in the Rodent Stomach

Transplantation of Enteric Cells Expressing p75 in the Rodent Stomach
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DOI:
10.1016/j.jss.2010.12.016
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发表时间:
2012-05-15
影响因子:
2.2
通讯作者:
Dunn, James C. Y.
Dunn, James C. Y.
中科院分区:
医学3区
文献类型:
--
作者:
Geisbauer, Carrie L.;Chapin, June C.;Dunn, James C. Y.

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背景资料。神经脊干细胞可能有潜力作为一种细胞疗法来重新填充肠道神经系统。低亲和力神经生长因子受体p75的表达可能会丰富从新生啮齿动物肠道分离的肠道细胞,以获得神经脊干细胞。虽然这些细胞在体外显示出巨大的前景,但它们在体内移植后是否会存活和分化仍有待确定。材料和方法。从新生啮齿动物肠肌分离出的细胞根据p75的表达程度进行分类。将亲本、p75高表达和p75低表达群体分别活体注入啮齿动物胃内7d。表达高水平p75的细胞也表达高水平的巢蛋白。对亲本、高p75和低p75细胞群体的评估显示,培养11d后,分别增长了420倍、130倍和20倍。将这些细胞群移植到同基因啮齿类动物的胃中,7d后细胞在注射部位存活。当亲代和p75高表达群体移植时,注射部位及其周围存在表达神经元标记外周蛋白或神经胶质标记S100的细胞。肠道细胞移植到啮齿类动物的胃中存活下来,并诱导注射部位及其周围的分化标志物的表达。基于这些结果,肠道细胞可能在各种胃肠道疾病中具有细胞治疗的潜力。(C)2012 Elsevier Inc.保留所有权利。
Background. Neural crest stem cells may hold potential as a cellular therapeutic to repopulate the enteric nervous system. The expression of the low-affinity nerve growth factor receptor, p75, may enrich enteric cells isolated from the neonatal rodent intestinal tract for neural crest stem cells. While these cells have shown tremendous promise in vitro, it remains to be determined whether they will survive and differentiate after in vivo transplantation.Materials and Methods. Cells isolated from the neonatal rodent intestinal muscularis were sorted according to their degree of p75 expression. The parent, p75-high, and p75-low expressing populations were injected into the rodent stomach for 7 d in vivo.Results. Cells that expressed high levels of p75 also expressed high levels of nestin. Evaluation of the parent, p75-high, and p75-low populations of cells showed 420-, 130-, and 20-fold growth, respectively, after 11 d of culture. Transplantation of these populations of cells into syngeneic rodent stomachs showed cell survival in the injection site after 7 d. Cells expressing either the neuronal marker, peripherin, or the glial marker, S100, were present in and around the injection site when the parent and the p75-high populations were transplanted.Conclusions. Enteric cells survive transplantation into the rodent stomach and induce the expression of differentiation markers in and around the injection site. Based on these results, enteric cells may hold potential as a cellular therapeutic in a variety of gastrointestinal disorders. (C) 2012 Elsevier Inc. All rights reserved.