Combination of hyaluronic acid and bone marrow mesenchymal stem cells promotes cardiac function after myocardial infarction

doi:10.3969/j.issn.2095-4344.0434

Abstract

Abstract:

BACKGROUND: The poor retention and survival of donor cells implanted into the myocardium limit the efficacy of cell therapy for myocardial infarction. Embedding cells in natural or synthetic biomaterials is a strategy to address this issue.
OBJECTIVE: To explore the effects of bone marrow mesenchymal stem cells (BMSCs) encapsulated in hyaluronic acid (HA) hydrogel on cardiac function after myocardial infarction.
METHODS: BMSCs from male Sprague-Dawley rats were isolated and cultured, and then HA-encapsulated BMSCs were cultured in vitro in the three-dimensional manner. A model of myocardial infarction was made by cutting the anterior descending artery of female Sprague-Dawley rats. After 1 week, the model rats were screened by ultrasonic testing and then eligible ones were randomly divided into four groups: PBS group (n=8), HA group (n=8), BMSCs group (n=29), and HA-encapsulated BMSCs group (n=29). At 1 week after modeling, the model rats underwent the secondary thoracotomy and the implants were injected into the marginal zone and infarcted region in corresponding groups. The survival rate and apoptosis of implanted cells were examined at post-injection day 1, week 1 and week 2 by RT-PCR and TUNEL respectively. At post-injection week 4, changes of cardiac microstructure and function were evaluated by histological examination and echocardiography.
RESULTS AND CONCLUSION: Compared with the BMSCs group, HA hydrogel significantly enhanced the survival rate and reduced the apoptotic rate of BMSCs at post-injection day 1 and week 2 (both P < 0.05). At post-injection week 4, the HA+BMSCs combined treatment yielded the best recovery of cardiac function (P < 0.05). To conclude, HA hydrogel can act as a vehicle for BMSCs delivery and improve the beneficial effects of implanted BMSCs in early myocardial repair (within 2 weeks after infarction) via enhancing cell retention and survival.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Myocardial Infarction, Bone Marrow, Mesenchymal Stem Cell Transplantation, Hyaluronic Acid, Tissue Engineering

CLC Number:

R394.2

Shang Qing-qing, Zhou Jian-ye, Li Kai, Sun Jia-kang, Meng Jian, Li Jun. Combination of hyaluronic acid and bone marrow mesenchymal stem cells promotes cardiac function after myocardial infarction[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(5): 675-679.

Figures/Tables 2

2.1 透明质酸水凝胶提高移植细胞的滞留存活率见图1。在体外，用透明质酸水凝胶包裹骨髓间充质干细胞在 35 mm培养皿中进行三维培养(图1A)。培养72 h时，没有细胞从透明质酸水凝胶中迁移到培养皿表面。在体内，RT-PCR结果(图1C)表明，移植1 d时，细胞+水凝胶组的细胞存活率(55.72±27.49)%明显高于单纯细胞组(7.66±5.6)%(P=0.041)；移植1周时，两组差异不明显[细胞+水凝胶组为(3.45±3.45)%，细胞组为(3.87±3.32)%，P=0.887]；移植2周时，细胞+水凝胶组的细胞存活率为(0.27±0.07)%，细胞组为(0.08±0.06)%，两组比较差异有显著性意义(P=0.025)。 TUNEL实验进一步证实：在移植1 d时，细胞+水凝胶组没有检测到细胞凋亡(图1F，表1)，而单纯细胞组细胞凋亡严重(图1D)，两组比较差异有显著性意义(P=0.017)；移植1周时，细胞+水凝胶组的细胞加速凋亡(图1H，表1)；移植2周时，两组细胞凋亡率差异无显著性意义(表1)。 2.2 心功能为了评价水凝胶与细胞组成的复合物对心功能的改善情况，移植后4周对各个实验组进行超声心动图检测，具体结果见表2。在移植前，4组的左室射血分数比较差异无显著性意义(P=0.323)。然而，移植后4周各组射血分数呈现出不同的变化：与移植前相比，PBS组的左室射血分数值显著降低，水凝胶组及细胞组的左室射血分数值差异不大，细胞+水凝胶组的左室射血分数值增高。细胞组左室射血分数的相对变化值与PBS组相比差异无显著性意义。水凝胶组的左室射血分数变化值与PBS组比，差异有显著性意义(P=0.023)。细胞+水凝胶组的左室射血分数相对变化值是最高的，与PBS组(P=0.001)及细胞组(P=0.026)相比差异有显著性意义。左室的短轴缩短率与射血分数呈现同样的变化趋势(表2)。"

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