Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Tamilnadu, India.
J Biomater Sci Polym Ed. 2020 Jan;31(1):123-140. doi: 10.1080/09205063.2019.1678796. Epub 2019 Oct 25.
India has an alarming rate of growth of cardiovascular diseases (CVD). Similar to cancer there is a significant role for epigenetic factors in the increasing prevalence of CVD. Targeting the epigenetic mechanism, viz., the DNA methylation processes, histone modifications, and RNA based arrangements is today considered as a potential therapeutic approach to CVD management. 5-Azacytidine is an epigenetic treatment drug that is involved in the demethylation of DNA. 5-Azacytidine is an FDA approved drug for myelodysplastic syndrome. However, the usage of 5-Azacytidine for CVD has not been found acceptable because of its poor stability in neutral solutions and shorter half-live which makes it toxic to the cells. A significant breakthrough in the use of 5-azacytidine for cell therapy and tissue engineering for CVD treatment has been gained based on its ability to differentiate mesenchymal stem cells into cardiomyocytes. This work addresses the further need for a sustained release of this drug, to reduce its toxicity to the stem cells. Electrospun PCL-gelatin fibres that are well aligned to provide a mat-like structure with sufficient porosity for differentiated cells to move forward have been synthesized. The crystalline character, porosity, fibre width, thermal behavior hydrophilicity of these scaffolds are in tune with those reported in the literature as ideal for cell proliferation and adhesion. FTIR measurements confirm the entrapment of 5-azacytidine on to the scaffold. The adsorption of the drug did not alter the characteristic features of the scaffold. Primary results on cell viability and cell morphology, as well as cardiomyocyte differentiation, have shown that PCL-gelatin scaffolds carrying 5-azacytidine developed in this work could serve as an ideal platform for mesenchymal stem cell differentiation into cardiomyocytes.
印度心血管疾病（CVD）的增长率令人担忧。与癌症类似，表观遗传因素在 CVD 患病率的增加中起着重要作用。针对表观遗传机制，即 DNA 甲基化过程、组蛋白修饰和基于 RNA 的排列，被认为是 CVD 管理的一种潜在治疗方法。5-氮杂胞苷是一种参与 DNA 去甲基化的表观遗传治疗药物。5-氮杂胞苷是一种获得 FDA 批准用于骨髓增生异常综合征的药物。然而，由于其在中性溶液中的稳定性差和半衰期较短，使其对细胞有毒性，因此 5-氮杂胞苷在 CVD 中的应用尚未被接受。基于其将间充质干细胞分化为心肌细胞的能力，5-氮杂胞苷在细胞治疗和 CVD 治疗组织工程中的应用取得了重大突破。这项工作进一步需要这种药物的持续释放，以降低其对干细胞的毒性。已经合成了具有良好对齐能力的 PCL-明胶纤维，以提供具有足够孔隙率的类似于垫子的结构，以使分化细胞向前移动。这些支架的结晶特性、孔隙率、纤维宽度、热行为和亲水性与文献中报道的理想用于细胞增殖和粘附的特性一致。FTIR 测量证实了 5-氮杂胞苷被包埋在支架上。药物的吸附并没有改变支架的特征。细胞活力和细胞形态以及心肌细胞分化的初步结果表明，在这项工作中开发的携带 5-氮杂胞苷的 PCL-明胶支架可以作为间充质干细胞分化为心肌细胞的理想平台。
