Human cardiomyocyte progenitor cell transplantation preserves long-term function of the infarcted mouse myocardium
Human cardiomyocyte progenitor cell transplantation preserves long-term function of the infarcted mouse myocardium
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DOI：
10.1093/cvr/cvp146
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发表时间：
2009-08-01
影响因子：
10.8
通讯作者：
Goumans, Marie-Jose
中科院分区：
文献类型：
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作者：
Smits, Anke M.;van Laake, Linda W.;Goumans, Marie-Jose
最近的临床研究表明，细胞移植对心脏功能的积极结果仅限于心肌梗死（MI）后的短期和中期恢复阶段，强调需要长期随访。这些瞬时效应可能取决于移植的细胞类型或其分化状态。我们已经确定了一个群体的心肌祖细胞（CMPCs）能够有效地分化为跳动的心肌细胞，内皮细胞，平滑肌细胞在体外。我们研究了CMPC或预分化的CMPC衍生的心肌细胞（CMPC-CM）是否能够恢复小鼠MI后受损的心肌。在免疫缺陷小鼠中诱导MI，然后心肌内注射CMPC、CMPC-CM或载体。使用9.4特斯拉磁共振成像纵向测量心肌梗死后3个月内的心脏功能。通过免疫组织化学确定人类细胞的命运。移植CMPCs或CMPC-CM导致更高的射血分数，并降低了心肌梗死后3个月的左心室重塑程度时，与车辆注射的动物。CMPCs和CMPC-CM产生了由人心肌细胞和血管组成的新心脏组织。CMPCs原位分化为与体外培养相同的细胞类型。这排除了体外预分化的需要，使CMPC成为基于（自体）细胞的治疗的有希望的来源。
Recent clinical studies revealed that positive results of cell transplantation on cardiac function are limited to the short- and mid-term restoration phase following myocardial infarction (MI), emphasizing the need for long-term follow-up. These transient effects may depend on the transplanted cell-type or its differentiation state. We have identified a population of cardiomyocyte progenitor cells (CMPCs) capable of differentiating efficiently into beating cardiomyocytes, endothelial cells, and smooth muscle cells in vitro. We investigated whether CMPCs or pre-differentiated CMPC-derived cardiomyocytes (CMPC-CM) are able to restore the injured myocardium after MI in mice.MI was induced in immunodeficient mice and was followed by intra-myocardial injection of CMPCs, CMPC-CM, or vehicle. Cardiac function was measured longitudinally up to 3 months post-MI using 9.4 Tesla magnetic resonance imaging. The fate of the human cells was determined by immunohistochemistry. Transplantation of CMPCs or CMPC-CM resulted in a higher ejection fraction and reduced the extent of left ventricular remodelling up to 3 months after MI when compared with vehicle-injected animals. CMPCs and CMPC-CM generated new cardiac tissue consisting of human cardiomyocytes and blood vessels. Fusion of human nuclei with murine nuclei was not observed.CMPCs differentiated into the same cell types in situ as can be obtained in vitro. This excludes the need for in vitro pre-differentiation, making CMPCs a promising source for (autologous) cell-based therapy.