Human cardiospheres are a source of stem cells with cardiomyogenic potential.
Human cardiospheres are a source of stem cells with cardiomyogenic potential.
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DOI：
10.1002/stem.413
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发表时间：
2010-05
期刊：
影响因子：
5.2
通讯作者：
Marban, Eduardo
中科院分区：
文献类型：
--
作者：
Davis, Darryl R.;Smith, Rachel Ruckdeschel;Marban, Eduardo
几个实验室已经表明，成年心脏干细胞的收集可以直接从心肌组织中生长[1-7]。扩增的细胞具有多能性和克隆性[3-5]。从心脏活组织检查中生长的细胞的球形聚集体，称为心脏球，在悬浮培养中自组装，并富含干细胞[1，6，7]。Andersen等人，在对新生鼠心脏组织的研究中，使用新的培养方法作为质疑心球培养干细胞的心源性潜力的基础[8]。我们认为，他们的全面结论不适用于使用既定方法的研究[1，2，6，7]。为了证实人心源性细胞（CDCs）在体内的心源性，我们评估了CDCs移植到梗死的严重联合免疫缺陷（SCID）小鼠后移植和形成新的心肌细胞的能力。人核抗原的免疫染色（1：50，Chemicon MAB 1281，Millipore，Billerica，MA，http：//www.微孔。com/）和慢病毒介导的绿色荧光蛋白（GFP）或β-半乳糖苷酶标记用于在注射后追踪细胞。尽管绝大多数CDCs可分布于梗死区（占总植入量的57% ± 3%）和近缘区（占30% ± 5%），但远缘区心肌也存在稳定的植入（占13% ± 3%）。图1A、1B显示了边界和梗塞区内的GFP标记的CDC。心肌肌钙蛋白I（cTnI; Chemicon MAB 3150）的复染证明许多CDC已分化为心肌细胞。如图1所示，小鼠心脏的部分由人CDC重建（图1A），而致密中心梗死区的CDC衍生心肌细胞仍然很小，细胞质中几乎没有cTnI表达（图1B）。人核抗原表达也证明了在边界区内源自移植的人CDC的分化的心肌细胞（图1C）。这些人源性细胞表达Cx43，表明但不能证明梗死组织内的功能整合（图1D）。然而，这种功能整合已经在体外用肌细胞-CDC共培养物严格记录[7]。此外，表达内皮细胞（血管性血友病因子[vWF];图1 E）和平滑肌细胞（α平滑肌肌动蛋白[aSMA];图1F）谱系标志物的β-半乳糖苷酶标记的CDC突出了CDC的体内多谱系潜力。
Several laboratories have shown that collection of adult cardiac stem cells can be grown directly from myocardial tissue [1–7]. Expanded cells are multipotent and clonogenic [3–5]. Spherical aggregates of cells grown from heart biopsies, termed cardiospheres, self-assemble in suspension culture and are enriched in stemness [1, 6, 7]. Andersen et al., in work on neonatal murine heart tissue, used novel culture methods as a basis to question the cardiogenic potential of cardiosphere-cultured stem cells [8]. We contend that their sweeping conclusions are not applicable to studies using established methods [1, 2, 6, 7]. To confirm the cardiogenic nature of human cardiospherederived cells (CDCs) in vivo, we evaluated the ability of CDCs to engraft and form new cardiomyocytes after transplantation into infarcted severe combined immunodeficiency (SCID) mice. Immunostaining for human nuclear antigen (1: 50, Chemicon MAB1281, Millipore, Billerica, MA, http://www. millipore. com/) and lentivirally mediated green fluorescent protein (GFP) or b-galactosidase labeling were used to track cells after injection. Although the majority of CDCs could be found throughout the infarct (57% 6 3% of the total engrafted) and the immediate border zone (30% 6 5%), stable engraftment also existed in the remote myocardium (13% 6 3%). Figure 1A, 1B shows GFP-labeled CDCs within the border and infarct zones. Counterstaining for cardiac troponin I (cTnI; Chemicon MAB3150) demonstrates that many CDCs have differentiated into cardiomyocytes. As shown in Figure 1, portions of the mouse heart were reconstituted by human CDCs (Fig. 1A), while CDC-derived cardiomyocytes in the dense central infarct zone remained small with little cTnI expression in their cytoplasm (Fig. 1B). Human nuclear antigen expression also demonstrates differentiated cardiomyocytes, derived from transplanted human CDCs, within the border zone (Fig. 1C). These human-derived cells express Cx43, suggesting, but not proving, functional integration within the infarcted tissue (Fig. 1D). Such functional integration has, however, been rigorously documented in vitro with myocyte-CDC coculture [7]. Further, b-galactosidase-labeled CDCs expressing markers of endothelial (Von Willebrand factor [vWF]; Fig. 1E) and smooth muscle (alpha smooth muscle actin [aSMA]; Fig. 1F) lineages highlight the in vivo multilineage potential of CDCs.
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影响因子：
3.7
作者：
Davis DR;Zhang Y;Smith RR;Cheng K;Terrovitis J;Malliaras K;Li TS;White A;Makkar R;Marbán E
通讯作者：
Marbán E
影响因子：
24
作者：
Terrovitis, John;Lautamaeki, Riikka;Bonios, Michael;Fox, James;Engles, James M.;Yu, Jianhua;Leppo, Michelle K.;Pomper, Martin G.;Wahl, Richard L.;Seidel, Jurgen;Tsui, Benjamin M.;Bengel, Frank M.;Abraham, M. Roselle;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
5.2
作者：
Andersen, Ditte Caroline;Andersen, Peter;Sheikh, Soren Paludan
通讯作者：
Sheikh, Soren Paludan
DOI：
10.1073/pnas.0706760104
发表时间：
2007-08-28
影响因子：
11.1
作者：
Bearzi, Claudia;Rota, Marcello;Anversa, Piero
通讯作者：
Anversa, Piero
影响因子：
20.1
作者：
Messina, E;De Angelis, L;Giacomello, A
通讯作者：
Giacomello, A