Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, 20 Geumo-ro, Mulgeum-eup, Yangsan, 50612, Republic of Korea.
Research Institute of Convergence Biomedical Science and Technology, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan, 50612, Republic of Korea.
Tissue Eng Regen Med. 2020 Jun;17(3):323-333. doi: 10.1007/s13770-020-00244-w. Epub 2020 Mar 29.
Despite promising advances in stem cell-based therapy, the treatment of ischemic cardiovascular diseases remains a big challenge due to both the insufficient in vivo viability of transplanted cells and poor angiogenic potential of stem cells. The goal of this study was to develop therapeutic human cardiac progenitor cells (hCPCs) for ischemic cardiovascular diseases with a novel M13 peptide carrier.
In this study, an engineered M13 peptide carrier was successfully generated using a QuikChange Kit. The cellular function of M13 peptide carrier-treated hCPCs was assessed using a tube formation assay and scratch wound healing assay. The in vivo engraftment and cell survival bioactivities of transplanted cells were demonstrated by immunohistochemistry after hCPC transplantation into a myocardial infarction animal model.
The engineered M13 peptide carrier, which expressed RGD peptide on PIII site and SDKP peptide on PVIII site, did not affect morphologic change and proliferation ability in hCPCs. In contrast, hCPCs treated with M13 showed enhanced angiogenic capacity, including tube formation and migration capacity. Moreover, transplanted hCPCs with M13 were engrafted into the ischemic region and promoted in vivo cell survival.
Our present data provides a promising protocol for CPC-based cell therapy via short-term cell priming of hCPCs with engineered M13 before cell transplantation for treatment of cardiovascular disease.
尽管基于干细胞的治疗有了令人鼓舞的进展,但由于移植细胞的体内存活率低和干细胞的血管生成潜力差,缺血性心血管疾病的治疗仍然是一个巨大的挑战。本研究的目的是开发一种新型 M13 肽载体治疗缺血性心血管疾病的治疗性人心脏祖细胞(hCPC)。
本研究使用 QuikChange 试剂盒成功地生成了工程化的 M13 肽载体。使用管形成测定法和划痕愈合测定法评估 M13 肽载体处理的 hCPC 的细胞功能。通过 hCPC 移植到心肌梗死动物模型后免疫组织化学,证明了移植细胞的体内植入和细胞存活生物活性。
表达在 PIII 位的 RGD 肽和在 PVIII 位的 SDKP 肽的工程化 M13 肽载体不会影响 hCPC 中的形态变化和增殖能力。相比之下,用 M13 处理的 hCPC 显示出增强的血管生成能力,包括管形成和迁移能力。此外,用 M13 移植的 hCPC 被植入缺血区域并促进体内细胞存活。
我们目前的数据为通过在细胞移植前用工程化的 M13 对 hCPC 进行短期细胞启动,为基于 CPC 的细胞治疗提供了一种有前途的方案,用于治疗心血管疾病。