Yuan Zihui, Cai Chuanqi, Qin You, Yan Kai, Wang Jian
Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Stem Cells Int. 2022 Aug 23;2022:6714765. doi: 10.1155/2022/6714765. eCollection 2022.
The homing of adipose-derived stem cells (ASCs) to infarcted myocardium, which is important for improved cardiac function, has been investigated previously, but with poor efficiency. Substantial improvements in engraftments are required to optimize ASC treatment. Stromal derived factor-1 (SDF-1) is upregulated early after MI, and its endogenous receptor, chemokine receptor 4 (CXCR4), is pivotal in stem cell survival, migration, and engraftment. We examined whether CXCR4 ASCs enhance their efficacy of migration and engraftment posttransplantation and improve heart function following myocardial infarction (MI).
CXCR4 ASC subpopulations were sorted by fluorescence-activated cell sorting. CXCR4 sorted ASCs exhibited the stronger cell viability, the faster proliferation rate, and the better migration capability in comparison with unfractionated ASCs. CXCR4 sorted ASCs secreted a higher level of angiogenic growth factors including VEGF, HGF, and IGF-1 relative to unfractionated ASCs. Fewer apoptotic cells under oxygen-glucose deprivation were detected in CXCR4 sorted ASCs than in unfractionated ASCs. Osteogenic and angiogenic differentiation were more pronounced in CXCR4 sorted ASCs than in unfractionated ASCs. At 3 days after acute MI, rats were randomly allocated to receive intramyocardial injection of cell culture medium, CXCR4 sorted ASCs, and unfractionated ASCs. Left ventricular function was assessed echocardiographically 4 weeks thereafter. Explanted hearts were then processed for the immunofluorescence detection of survived cells, quantification of angiogenesis, and cell engraftment. CXCR4 sorted ASCs more obviously engrafted into infarcted myocardium, more markedly inhibited collagen remodeling, and more effectively improved heart function and promoted capillary formation than did unfractionated ASCs.
CXCR4 sorted ASCs are superior to unfractionated ASCs due to better viability, faster proliferation, more cytokine secretion, and stronger migration. CXCR4 sorted ASCs provide better curative benefits on MI than do unfractionated ASCs and can be efficiently harvested and purified from adipose tissue, they may serve as a promising candidate for MI.
脂肪来源干细胞（ASC）归巢至梗死心肌对改善心脏功能很重要，此前已有相关研究，但效率较低。需要大幅提高移植效率以优化ASC治疗。基质细胞衍生因子-1（SDF-1）在心肌梗死（MI）后早期上调，其内源性受体趋化因子受体4（CXCR4）在干细胞存活、迁移和移植中起关键作用。我们研究了CXCR4 ASC是否能提高其移植后迁移和植入的效果，并改善心肌梗死后的心脏功能。
通过荧光激活细胞分选对CXCR4 ASC亚群进行分选。与未分选的ASC相比，分选后的CXCR4 ASC表现出更强的细胞活力、更快的增殖速率和更好的迁移能力。相对于未分选的ASC，分选后的CXCR4 ASC分泌更高水平的血管生成生长因子，包括VEGF、HGF和IGF-1。在氧-葡萄糖剥夺条件下，分选后的CXCR4 ASC中检测到的凋亡细胞比未分选的ASC少。分选后的CXCR4 ASC比未分选的ASC具有更明显的成骨和成血管分化。急性心肌梗死后3天，将大鼠随机分配接受心肌内注射细胞培养基、分选后的CXCR4 ASC和未分选的ASC。此后4周通过超声心动图评估左心室功能。然后取出心脏进行存活细胞的免疫荧光检测、血管生成定量和细胞植入分析。与未分选的ASC相比，分选后的CXCR4 ASC更明显地植入梗死心肌，更显著地抑制胶原重塑，更有效地改善心脏功能并促进毛细血管形成。
分选后的CXCR4 ASC由于具有更好的活力、更快的增殖、更多的细胞因子分泌和更强的迁移能力，优于未分选的ASC。分选后的CXCR4 ASC在心肌梗死治疗上比未分选的ASC具有更好的疗效，并且可以从脂肪组织中高效收获和纯化，它们可能是心肌梗死治疗的一个有前途的候选者。
