Assessment of human MAPCs for stem cell transplantation and cardiac regeneration after myocardial infarction in SCID mice
Assessment of human MAPCs for stem cell transplantation and cardiac regeneration after myocardial infarction in SCID mice
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DOI：
10.1016/j.exphem.2010.06.013
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发表时间：
2010-11-01
影响因子：
2.6
通讯作者：
Franz, Wolfgang M.
中科院分区：
文献类型：
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作者：
Dimomeletis, Ilias;Deindl, Elisabeth;Franz, Wolfgang M.
目的临床研究表明，心肌梗死（MI）后全骨髓（BM）移植是可行的，聚焦于确定的BM来源的干细胞类型可以实现更特异性和优化的治疗多谱系分化潜能使得BM来源的多能成体祖细胞（MAPCs）一个有希望的用于再生目的的干细胞库我们分析了人MAPCs在心肌梗死小鼠模型中的心脏再生潜力材料和方法通过CD 45（在体外，通过逆转录聚合酶链反应分析干细胞。在体内，我们移植人MAPCs，在严重联合免疫缺陷（SCID）米色小鼠MI后心肌内注射（5 × 10（5））。手术后6天和30天，在体内研究了压力-容积关系，对心脏组织进行了化学分析。结果对早期人MAPC传代的逆转录聚合酶链反应实验证明了Oct-4的表达，Oct-4是一种指示多能性的干细胞标记物。在以后的传代中，心脏标志物（Nkx 2 5、GATA 4、MLC 2 v、MLC 2a、ANP、cTnT、cTnI）和平滑肌细胞标志物（SMA、SM 22 α）表达将人MAPC移植到MI后的缺血边缘区导致第6天心脏功能改善（射血分数，26% vs 20%）和第30天（射血分数，30%对23%）在免疫组织化学中证实人MAPC标记波形蛋白，证明人MAPC整合在pen区。免疫组化和畸胎瘤形成均未发现，表明移植的人MAPCs在肿瘤敏感的SCID模型中没有成瘤潜力。结论MI后移植人MAPCs改善了心肌功能，这可以通过人MAPCs的营养作用来解释。敏感的SCID模型表明，人MAPCs可以提供有效和安全的干细胞库，用于缺血性心脏病的潜在治疗（C）。2010年ISEH血液学和干细胞学会由Elsevier Inc出版
Objective Clinical studies suggest that transplantation of total bone marrow (BM) after myocardial infarction (MI) is feasible and potentially effective However, focusing on a defined BM derived stem cell type may enable a more specific and optimized treatment Multilineage differentiation potential makes BM derived multipotent adult progenitor cells (MAPCs) a promising stem cell pool for regenerative purposes We analyzed the cardioregenerative potential of human MAPCs in a murine model of myocardial infarctionMaterials and Methods Human MAPCs were selected by negative depletion of CD45(+)/glyco phorin(+) BM cells and plated on fibronectin-coated dishes In vitro, stem cells were analyzed by reverse transcription polymerase chain reaction In vivo, we transplanted human MAPCs (5 x 10(5)) by intramyocardial injection after MI in severe combined immunodeficient (SCID) beige mice Six and 30 days after the surgical procedure, pressure-volume relationships were investigated in vivo Heart tissues were analyzed immunohistochemicallyResults Reverse transcription polymerase chain reaction experiments on early human MAPC passages evidenced an expression of Oct-4, a stem cell marker indicating pluripotency In later passages, cardiac markers (Nkx2 5, GATA4, MLC 2v, MLC 2a, ANP, cTnT, cTnI,) and smooth muscle cell markers (SMA, SM22 alpha) were expressed Transplantation of human MAPCs into the ischemic border zone after MI resulted in an improved cardiac function at day 6 (ejection fraction, 26% vs 20%) and day 30 (ejection fraction, 30% vs 23%) Confirmation of human MAPC marker vimentin in immunohistochemistry demonstrated that human MAPC Integrated in the pen Infarct region The proliferation marker Ki67 was absent in immunohistochemistry and teratoma formation was not found, indicating no tumorous potential of transplanted human MAPCs in the tumor sensitive SCID modelConclusions Transplantation of human MAPCs after MI ameliorates myocardial function, which may be explained by trophic effects of human MAPCs Lack of evidence of tumorous potential in the tumor-sensitive SCID model indicates that human MAPCs may deliver an effective and safe stem cell pool for potential treatment of ischemic heart disease (C) 2010 ISEH Society for Hematology and Stem Cells Published by Elsevier Inc