Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran 1449614535, Iran.
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
Biomolecules. 2020 Jan 30;10(2):205. doi: 10.3390/biom10020205.
Biomaterials in conjunction with stem cell therapy have recently attracted attention as a new therapeutic approach for myocardial infarction (MI), with the aim to solve the delivery challenges that exist with transplanted cells. Self-assembling peptide (SAP) hydrogels comprise a promising class of synthetic biomaterials with cardiac-compatible properties such as mild gelation, injectability, rehealing ability, and potential for sequence modification. Herein, we developed an SAP hydrogel composed of a self-assembling gel-forming core sequence (RADA) modified with SDKP motif with pro-angiogenic and anti-fibrotic activity to be used as a cardioprotective scaffold. The RADA-SDKP hydrogel was intramyocardially injected into the infarct border zone of a rat model of MI induced by left anterior descending artery (LAD) ligation as a cell-free or a cell-delivering scaffold for bone marrow mesenchymal stem cells (BM-MSCs). The left ventricular ejection fraction (LVEF) was markedly improved after transplantation of either free hydrogel or cell-laden hydrogel. This cardiac functional repair coincided very well with substantially lower fibrotic tissue formation, expanded microvasculature, and lower inflammatory response in the infarct area. Interestingly, BM-MSCs alone or in combination with hydrogel could not surpass the cardiac repair effects of the SDKP-modified SAP hydrogel. Taken together, we suggest that the RADA-SDKP hydrogel can be a promising cell-free construct that has the capability for functional restoration in the instances of acute myocardial infarction (AMI) that might minimize the safety concerns of cardiac cell therapy and facilitate clinical extrapolation.
生物材料与干细胞疗法相结合，最近作为心肌梗死（MI）的一种新的治疗方法引起了关注，目的是解决移植细胞所存在的输送挑战。自组装肽（SAP）水凝胶是一类很有前途的合成生物材料，具有心脏相容的特性，如温和的凝胶化、可注射性、再修复能力和序列修饰的潜力。在此，我们开发了一种由具有促血管生成和抗纤维化活性的 SDKP 基序修饰的自组装凝胶形成核心序列（RADA）组成的 SAP 水凝胶，用作心脏保护支架。RADA-SDKP 水凝胶被心肌内注射到由左前降支（LAD）结扎诱导的 MI 大鼠模型的梗死边界区，作为无细胞或骨髓间充质干细胞（BM-MSCs）的输送支架。左心室射血分数（LVEF）在游离水凝胶或细胞负载水凝胶移植后明显提高。这种心脏功能修复与梗死区纤维化组织形成显著减少、微血管扩张和炎症反应降低非常吻合。有趣的是，单独的 BM-MSCs 或与水凝胶联合使用，都不能超过 SDKP 修饰的 SAP 水凝胶的心脏修复效果。总之，我们认为 RADA-SDKP 水凝胶可以作为一种有前途的无细胞构建物，具有在急性心肌梗死（AMI）情况下恢复功能的能力，这可能最小化心脏细胞治疗的安全问题，并促进临床推广。
