Expression of cardiomyocytic markers on adipose tissue-derived cells in a murine model of acute myocardial injury
Expression of cardiomyocytic markers on adipose tissue-derived cells in a murine model of acute myocardial injury
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DOI：
10.1080/14653240510027226
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发表时间：
2005-07-01
期刊：
影响因子：
4.5
通讯作者：
Fraser, JK
中科院分区：
文献类型：
--
作者：
Strem, BM;Zhu, M;Fraser, JK
背景：动物和早期临床研究表明，冠状动脉内注射自体骨髓来源的细胞可改善心肌梗死后的预后。对培养的骨髓基质细胞(MSC)的动物研究也提供了类似的数据。在脂肪组织中已经发现了具有类似于MSC特性的细胞。在这些观察的基础上，本研究的目的是确定脂肪组织衍生细胞在体内是否也会在心肌损伤的情况下经历类似的分化。方法从rosa26小鼠的皮下脂肪组织(几乎在所有组织中都表达β-半乳糖苷酶基因)分离ADC，并在诱导心肌冷冻损伤后立即注射到B6129S受体小鼠的脑室内。分别于术后24小时、7天和14天处死受者，观察供体来源的细胞在心脏内的存在情况。结果在ADC处理的动物的梗死灶中发现了β-半乳糖阳性细胞。未损伤的心肌和对照动物的梗死灶均未见染色。免疫组织化学分析显示，β-半乳糖苷酶与肌球蛋白重链、NKX2.5和肌钙蛋白I共表达，而与连接蛋白43、CD31、von Willebrand因子、MyoD或CD45未检测到共表达。结论脂肪组织中含有能够植入受损心肌的细胞群，这种植入与供体来源细胞表达心肌细胞标志物有关。
Background Animal and early clinical studies have provided evidence suggesting that intracoronary administration of autologous bone marrow-derived cells results in improved outcome following myocardial infarction. Animal studies with cultured marrow stromal cells (MSC) have provided similar data. Cells with properties that are similar to MSC have been identified in adipose tissue. Other groups have demonstrated in vivo differentiation of adipose tissue-derived cells (ADC) into cells exhibiting biochemical and functional markers of cardiac myocytes, including spontaneous beating.Hypothesis Based on these observations, the objective of the present study was to determine whether ADC might undergo similar differentiation in vivo in the context of myocardial injury.Methods ADC were isolated from subcutaneous adipose tissue of Rosa26 mice (which express the beta-galactosidase transgene in almost every tissue) and injected into the intraventricular chamber of B6129S recipient mice immediately following induction of myocardial cryoinjury. Groups of recipients were euthanized at 24 hours, 7 and 14 days post surgery and examined for the presence of donor-derived cells within the heart.Results Beta-gal positive cells were identified in the infarcts of ADC-treated animals. No staining was observed in uninjured myocardium or in infarcts of control animals. Immunohistochemical analysis revealed co-expression of beta-gal with Myosin Heavy Chain, Nkx2.5 and with Troponin I. Co-expression of beta-galactosidase with Connexin 43, CD31, von Willebrand factor, MyoD or CD45 was not detected.Conclusion Thus, these data indicate that adipose tissue contains a population of cells that has the ability to engraft injured myocardium and that this engraftment is associated with expression of cardiomyocytic markers by donor-derived cells.