Cardiotrophic Growth Factor-Driven Induction of Human Muse Cells Into Cardiomyocyte-Like Phenotype.
Cardiotrophic Growth Factor-Driven Induction of Human Muse Cells Into Cardiomyocyte-Like Phenotype.
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DOI：
10.1177/0963689717721514
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发表时间：
2018-03
影响因子：
3.3
通讯作者：
Dezawa M
中科院分区：
文献类型：
--
作者：
Amin M;Kushida Y;Wakao S;Kitada M;Tatsumi K;Dezawa M
多系分化应激耐受(MUSE)细胞是一种内源性非肿瘤干细胞，可作为阶段特异性胚胎抗原3(SSEA-3)+从包括骨髓在内的各种器官中收集，并具有多能样特性。评估了人骨髓来源的MUSE细胞转化为心脏系细胞的潜力。我们发现：(1)在悬浮培养中，5‘-氮胞苷成功地加速了心脏标志物NKX2.5启动子的去甲基化；(2)将细胞转移到贴壁培养上，并用早期心脏分化因子包括无翼肌钙蛋白(WNT)-3a、骨形态发生蛋白-2/4和转化生长因子β-1处理；(3)进一步用包括心肌营养素-1在内的晚期心脏分化细胞因子将MUSE细胞转化为表达α-肌动蛋白和肌钙蛋白-I的心肌细胞样细胞。最后一步的MLC2a表达提示细胞分化为心房亚型。当Dickkopf相关蛋白1(DKK-1)和Noggin(Wnt3a和BMP-4的抑制剂)分别在步骤(2)和(3)处理细胞时，MLC2v表达成熟的心室亚型的标志。所有步骤都不包括外源基因导入，使诱导细胞在未来的临床应用中是可行的。
Multilineage-differentiating stress-enduring (Muse) cells are endogenous nontumorigenic stem cells collectable as stage-specific embryonic antigen 3 (SSEA-3) + from various organs including the bone marrow and are pluripotent-like. The potential of human bone marrow-derived Muse cells to commit to cardiac lineage cells was evaluated. We found that (1) initial treatment of Muse cells with 5′-azacytidine in suspension culture successfully accelerated demethylation of cardiac marker Nkx2.5 promoter; (2) then transferring the cells onto adherent culture and treatment with early cardiac differentiation factors including wingless-int (Wnt)-3a, bone morphogenetic proteins (BMP)-2/4, and transforming growth factor (TGF) β1; and (3) further treatment with late cardiac differentiation cytokines including cardiotrophin-1 converted Muse cells into cardiomyocyte-like cells that expressed α-actinin and troponin-I with a striation-like pattern. MLC2a expression in the final step suggested differentiation of the cells into an atrial subtype. MLC2v, a marker for a mature ventricular subtype, was expressed when cells were treated with Dickkopf-related protein 1 (DKK-1) and Noggin, inhibitors of Wnt3a and BMP-4, respectively, between steps (2) and (3). None of the steps included exogenous gene transfection, making induced cells feasible for future clinical application.
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影响因子：
24
作者：
Bartunek, Jozef;Behfar, Atta;Terzic, Andre
通讯作者：
Terzic, Andre
DOI：
10.1073/pnas.0911647107
发表时间：
2010-05-11
影响因子：
11.1
作者：
Kuroda, Yasumasa;Kitada, Masaaki;Dezawa, Mari
通讯作者：
Dezawa, Mari
DOI：
10.1073/pnas.1121236109
发表时间：
2012-07-03
影响因子：
11.1
作者：
Klaus, Alexandra;Mueller, Marion;Birchmeier, Walter
通讯作者：
Birchmeier, Walter
影响因子：
--
作者：
Capasso S;Alessio N;Squillaro T;Di Bernardo G;Melone MA;Cipollaro M;Peluso G;Galderisi U
通讯作者：
Galderisi U
化学和物理刺激诱导心肌细胞从干细胞分化
DOI：
10.1016/j.bbrc.2009.01.173
发表时间：
2009-04-10
影响因子：
3.1
作者：
Ge, Dongxia;Liu, Xiaojing;Chen, Huaiqing
通讯作者：
Chen, Huaiqing