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新生鼠睾丸多能生殖干细胞改善急性缺血性心脏病模型小鼠的心脏功能。

Neonatal mouse testis-derived multipotent germline stem cells improve the cardiac function of acute ischemic heart mouse model.

机构信息

Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.

出版信息

Biochem Biophys Res Commun. 2010 Sep 10;400(1):27-33. doi: 10.1016/j.bbrc.2010.07.131. Epub 2010 Aug 4.

Abstract

Multipotent germline stem (mGS) cells have been established from neonatal mouse testes. We previously reported that undifferentiated mGS cells are phenotypically similar to embryonic stem cells and that fetal liver kinase 1 (Flk1)(+) mGS cells have a similar potential to differentiate into cardiomyocytes and endothelial cells compared with Flk1(+) embryonic stem cells. Here, we transplanted these Flk1(+) mGS cells into an ischemic heart failure mouse model to evaluate the improvement in cardiac function. Significant increase in left ventricular wall thickness of the infarct area, left ventricular ejection fraction and left ventricular maximum systolic velocity was observed 4weeks after when sorted Flk1(+) mGS cells were transplanted directly into the hearts of the acute ischemic model mice. Although the number of cardiomyocytes derived from Flk1(+) mGS cells were too small to account for the improvement in cardiac function but angiogenesis around ischemic area was enhanced in the Flk1(+) mGS cells transplanted group than the control group and senescence was also remarkably diminished in the early phase of ischemia according to β-galactosidase staining assay. In conclusion, Flk1(+) mGS cell transplantation can improve the cardiac function of ischemic hearts by promoting angiogenesis and by delaying host cell death via senescence.

摘要

多能生殖细胞(mGS)干细胞已从小鼠睾丸中建立。我们之前报道称,未分化的 mGS 细胞表型上与胚胎干细胞相似,并且与 Flk1(+)胚胎干细胞相比,胎肝激酶 1(Flk1)(+)mGS 细胞具有类似的分化为心肌细胞和内皮细胞的潜能。在这里,我们将这些 Flk1(+)mGS 细胞移植到缺血性心力衰竭小鼠模型中,以评估对心脏功能的改善。当将分选的 Flk1(+)mGS 细胞直接移植到急性缺血模型小鼠的心脏中 4 周后,观察到梗死区左心室壁厚度、左心室射血分数和左心室最大收缩速度明显增加。虽然源自 Flk1(+)mGS 细胞的心肌细胞数量太少,无法解释心脏功能的改善,但与对照组相比,Flk1(+)mGS 细胞移植组缺血区域周围的血管生成增强,并且根据β-半乳糖苷酶染色检测,衰老也在缺血早期显著减少。总之,Flk1(+)mGS 细胞移植可通过促进血管生成和通过衰老延迟宿主细胞死亡来改善缺血心脏的心脏功能。

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