Haneef Kanwal, Naeem Nadia, Khan Irfan, Iqbal Hana'a, Kabir Nurul, Jamall Siddiqua, Zahid Muniza, Salim Asmat
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Mol Biol Rep. 2014 May;41(5):3099-112. doi: 10.1007/s11033-014-3170-1. Epub 2014 Jan 28.
Mesenchymal stem cells (MSCs) show accelerated regeneration potential when these cells experience hypoxic stress. This "preconditioning" has shown promising results with respect to cardio-protection as it stimulates endogenous mechanisms resulting in multiple cellular responses. The current study was carried out to analyze the effect of hypoxia on the expression of certain growth factors in rat MSCs and cardiomyocytes (CMs). Both cell types were cultured and assessed separately for their responsiveness to hypoxia by an optimized dose of 2,4,-dinitrophenol (DNP). These cells were allowed to propagate under normal condition for either 2 or 24 h and then analyzed for the expression of growth factors by RT-PCR. Variable patterns of expression were observed which indicate that their expression depends on the time of re-oxygenation and extent of hypoxia. To see whether the growth factors released during hypoxia affect the fusion of MSCs with CMs, we performed co-culture studies in normal and conditioned medium. The conditioned medium is defined as the medium in which CMs were grown for re-oxygenation till the specified time period of either 2 or 24 h after hypoxia induction. The results showed that the fusion efficiency of cells was increased when the conditioned medium was used as compared to that in the normal medium. This may be due to the presence of certain growth factors released by the cells under hypoxic condition that promote cell survival and enhance their fusion or regenerating ability. This study would serve as another attempt in designing a therapeutic strategy in which conditioned MSCs can be used for ischemic diseases and provide more specific therapy for cardiac regeneration.
间充质干细胞(MSCs)在经历缺氧应激时显示出加速的再生潜力。这种“预处理”在心脏保护方面已显示出有希望的结果,因为它刺激内源性机制,导致多种细胞反应。本研究旨在分析缺氧对大鼠间充质干细胞和心肌细胞(CMs)中某些生长因子表达的影响。两种细胞类型分别进行培养,并通过优化剂量的2,4-二硝基苯酚(DNP)评估它们对缺氧的反应性。这些细胞在正常条件下培养2或24小时,然后通过逆转录聚合酶链反应(RT-PCR)分析生长因子的表达。观察到了不同的表达模式,这表明它们的表达取决于复氧时间和缺氧程度。为了观察缺氧期间释放的生长因子是否影响间充质干细胞与心肌细胞的融合,我们在正常培养基和条件培养基中进行了共培养研究。条件培养基定义为心肌细胞在缺氧诱导后复氧直至指定的2或24小时时间段内生长的培养基。结果表明,与正常培养基相比,使用条件培养基时细胞的融合效率增加。这可能是由于缺氧条件下细胞释放的某些生长因子的存在,这些生长因子促进细胞存活并增强其融合或再生能力。本研究将作为设计一种治疗策略的又一次尝试,其中经预处理的间充质干细胞可用于治疗缺血性疾病,并为心脏再生提供更具特异性的治疗方法。