Rabbani Shahram, Soleimani Masoud, Sahebjam Mohammad, Imani Mohammad, Haeri Azadeh, Ghiaseddin Ali, Nassiri Seyed Mahdi, Majd Ardakani Jalil, Tajik Rostami Maryam, Jalali Arash, Ahmadi Tafti Seyed Hossein
Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences,Tehran,Iran.
Department of Hematology, Tarbiat Modares University, Tehran, Iran.
Iran J Pharm Res. 2018 Spring;17(2):426-441.
Wharton's jelly mesenchymal stem cells (HWJMSCs) hold promise for myocardial regeneration, but optimal treatment regimen (preferably with a growth factor) is required to maximize functional benefits. The aim of this study was to explore the cardioprotective and angiogenesis effects of HWJMSCs combined with insulin-like growth factor-1 (IGF-1) in the treatment of acute myocardial infarction. The hydrogel consisted of Polyethylene glycol (PEG) and hyaluronic acid was prepared and characterized with regards to rheology, morphology, swelling, degradation, and release behaviors. To examine effects, the hydrogels containing HWJMSCs either alone (Cells/hydrogel group) or with IGF-1 (Cells/hydrogel/IGF-1 group) were intra-myocardially injected into a rabbit myocardial infarction model. efficacy was evaluated histological, immunohistochemical, echocardiography, scanning electron microscopy, and SPECT analyses. Eight weeks after infusion, the Cells/hydrogel and Cells/hydrogel/IGF-1 groups exhibited significantly increased left ventricular ejection fraction by echocardiography. Percent of ejection fraction was respectively 18.5% and 40% greater than control ( < 0.01). Vascular density (CD31 positive cells) of both treatment groups were more than the control group and this superiority was more remarkable in Cells/hydrogel/IGF-1 group. Cells/hydrogel/IGF-1 group showed the least defect size in SPECT analysis. Combinatory therapy with HWJMSCs and IGF-1 may additionally improve cardiac function and promote angiogenesis.
华顿胶间充质干细胞(HWJMSCs)有望用于心肌再生,但需要最佳治疗方案(最好使用生长因子)以最大化功能效益。本研究的目的是探讨HWJMSCs联合胰岛素样生长因子-1(IGF-1)在治疗急性心肌梗死中的心脏保护和血管生成作用。制备了由聚乙二醇(PEG)和透明质酸组成的水凝胶,并对其流变学、形态学、溶胀、降解和释放行为进行了表征。为了检验效果,将单独含有HWJMSCs的水凝胶(细胞/水凝胶组)或含有IGF-1的水凝胶(细胞/水凝胶/IGF-1组)心肌内注射到兔心肌梗死模型中。通过组织学、免疫组织化学、超声心动图、扫描电子显微镜和单光子发射计算机断层显像(SPECT)分析评估疗效。输注8周后,细胞/水凝胶组和细胞/水凝胶/IGF-1组经超声心动图检查显示左心室射血分数显著增加。射血分数百分比分别比对照组高18.5%和40%(P<0.01)。两个治疗组的血管密度(CD31阳性细胞)均高于对照组,且这种优势在细胞/水凝胶/IGF-1组中更为显著。细胞/水凝胶/IGF-1组在SPECT分析中显示梗死面积最小。HWJMSCs与IGF-1联合治疗可能会进一步改善心脏功能并促进血管生成。