Xenotransplantation of Long-Term-Cultured Swine Bone Marrow-Derived Mesenchymal Stem Cells

间充质干细胞 心肌梗塞 生物 移植 骨髓 人口 细胞疗法 干细胞 免疫学 男科 心脏病学 内科学 医学 细胞生物学 环境卫生
作者
Yasuhiro Nakamura,Xiaohong Wang,ChengSu Xu,Atsushi Asakura,Minoru Yoshiyama,Arthur H. L. From,Jianyi Zhang
出处
期刊:Stem Cells [Wiley]
卷期号:25 (3): 612-620 被引量:107
标识
DOI:10.1634/stemcells.2006-0168
摘要

Abstract Swine-derived MSCs were efficiently isolated and extensively expanded using a low fetal serum content growth medium to which selected growth factors were added. After ≥96 cell population doublings (PDs), MSCs were devoid of cytogenetic abnormalities. In vitro chondrogenic and osteogenic differentiation capacity was preserved after 80 PDs. To test therapeutic efficacy, 1 × 106 80-PD MSCs were injected directly into the peri-infarct zone of hearts of immunodeficient (non-obese diabetic/severe combined immunodeficient) mice at the time of acute myocardial infarction. Engrafted MSCs survived in the infarcted hearts for at least 4 weeks. Echocardiography at 2 and 4 weeks postinfarction revealed a significant preservation of the left ventricular ejection fractions of infarct hearts receiving MSCs compared with infarct hearts receiving saline. Peri-infarct zone capillarity was better preserved in MSC-treated hearts than other infarct groups of hearts, but infarct size was comparable in all groups. Only rare engrafted MSCs expressed cardiac-specific or endothelial cell-specific markers. Hence, 80-PD MSCs retained the capacity to promote functional improvement in the infarcted heart despite minimal differentiation of MSCs into cardiomyocytes or endothelial cells. These data suggest that the beneficial effects of MSC transplantation most likely result from the trophic effects of MSC-released substances on native cardiac and vascular cells. The capacity to massively expand MSC lines without loss of therapeutic efficacy may prove to be useful in the clinical setting where “off the shelf” MSCs may be required for interventions in patients with acute coronary syndromes.

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