Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium.
Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium.
复制标题
DOI：
10.1084/jem.20061469
复制
发表时间：
2006-10-02
期刊：
影响因子：
--
通讯作者：
Fleischmann BK
中科院分区：
文献类型：
--
作者：
Kolossov E;Bostani T;Roell W;Breitbach M;Pillekamp F;Nygren JM;Sasse P;Rubenchik O;Fries JW;Wenzel D;Geisen C;Xia Y;Lu Z;Duan Y;Kettenhofen R;Jovinge S;Bloch W;Bohlen H;Welz A;Hescheler J;Jacobsen SE;Fleischmann BK
细胞性心肌成形术是治疗严重心力衰竭的一种有吸引力的选择。然而，哪种细胞来源最有前景仍不明确且存在争议。因此，我们研究并检测了骨髓（BM）细胞以及胚胎干细胞（ES细胞）衍生的心肌细胞在移植到梗死小鼠心脏后的命运和功能影响。对于ES细胞来说，这尤其具有挑战性，因为人们对其向心肌细胞的富集以及长期植入和致瘤性仍知之甚少。我们构建了在心脏特异性启动子控制下表达嘌呤霉素抗性和增强型绿色荧光蛋白基因盒的转基因ES细胞。嘌呤霉素筛选产生了高度纯化（>99%）的心肌细胞群，并且由于纯化时诱导了增殖，心肌细胞的产量增加了6 - 10倍。当将筛选出的ES细胞衍生的心肌细胞和成纤维细胞共同移植到同基因小鼠的受损心脏中时，观察到了长期植入（4 - 5个月），并且未发现畸胎瘤形成（n = 60）。尽管ES细胞衍生的心肌细胞移植改善了心脏功能，但骨髓细胞没有积极作用。此外，未检测到骨髓细胞对心脏、内皮或平滑肌新生的贡献。因此，我们的结果表明，基于ES细胞的疗法是治疗心肌功能受损的一种有前景的方法，并且比骨髓来源的细胞效果更好。
Cellular cardiomyoplasty is an attractive option for the treatment of severe heart failure. It is, however, still unclear and controversial which is the most promising cell source. Therefore, we investigated and examined the fate and functional impact of bone marrow (BM) cells and embryonic stem cell (ES cell)–derived cardiomyocytes after transplantation into the infarcted mouse heart. This proved particularly challenging for the ES cells, as their enrichment into cardiomyocytes and their long-term engraftment and tumorigenicity are still poorly understood. We generated transgenic ES cells expressing puromycin resistance and enhanced green fluorescent protein cassettes under control of a cardiac-specific promoter. Puromycin selection resulted in a highly purified (>99%) cardiomyocyte population, and the yield of cardiomyocytes increased 6–10-fold because of induction of proliferation on purification. Long-term engraftment (4–5 months) was observed when co-transplanting selected ES cell–derived cardiomyocytes and fibroblasts into the injured heart of syngeneic mice, and no teratoma formation was found (n = 60). Although transplantation of ES cell–derived cardiomyocytes improved heart function, BM cells had no positive effects. Furthermore, no contribution of BM cells to cardiac, endothelial, or smooth muscle neogenesis was detected. Hence, our results demonstrate that ES-based cell therapy is a promising approach for the treatment of impaired myocardial function and provides better results than BM-derived cells.
登录
查看更多内容
DOI：
10.1083/jcb.143.7.2045
发表时间：
1998-12-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kolossov E;Fleischmann BK;Liu Q;Bloch W;Viatchenko-Karpinski S;Manzke O;Ji GJ;Bohlen H;Addicks K;Hescheler J
通讯作者：
Hescheler J
影响因子：
6
作者：
Laflamme, MA;Gold, J;Murry, CE
通讯作者：
Murry, CE
DOI：
10.1073/pnas.1232447100
发表时间：
2003-06-24
影响因子：
11.1
作者：
Léobon, B;Garcin, I;Charpak, S
通讯作者：
Charpak, S
影响因子：
64.8
作者：
Murry, CE;Soonpaa, MH;Field, LJ
通讯作者：
Field, LJ
影响因子：
168.9
作者：
Janssens, S;Dubois, C;Van de Werf, F
通讯作者：
Van de Werf, F