Sci Rep. 2020 May 15;10(1):8061. doi: 10.1038/s41598-020-64908-2. Mammalian CBX7 isoforms p36 and p22 exhibit differential responses to serum, varying functions for proliferation, and distinct subcellular localization Kyu-Won Cho # 1, Mark Andrade # 1, Yu Zhang 1, Young-Sup Yoon 2 3 4 PMID: 32415167 PMCID: PMC7228926 DOI: 10.1038/s41598-020-64908-2 Abstract CBX7 is a polycomb group protein, and despite being implicated in many diseases, its role in cell proliferation has been controversial: some […]

Circ Res. 2019 Dec 6;125(12):1141-1145. doi: 10.1161/CIRCRESAHA.119.310859. Epub 2019 Dec 5. Current State of Cardiovascular Research in Korea Jae Il Shin 1 2, Jaewon Oh 3, Hyeon Chang Kim 4, Donghoon Choi 3, Young-Sup Yoon 5 2Affiliations expand PMID: 31804914 PMCID: PMC7008968 DOI: 10.1161/CIRCRESAHA.119.310859 Free PMC article Abstract Cardiovascular diseases have shown a continuous increase in Korea over the past decade and became the second most common cause of mortality in Korea. Although […]

Nat Methods. 2019 Nov;16(11):1169-1175. doi: 10.1038/s41592-019-0586-5. Epub 2019 Oct 7. Engineering of human brain organoids with a functional vascular-like system Bilal Cakir # 1, Yangfei Xiang # 1, Yoshiaki Tanaka 1, Mehmet H Kural 2, Maxime Parent 3, Young-Jin Kang 4 5, Kayley Chapeton 6, Benjamin Patterson 1, Yifan Yuan 2, Chang-Shun He 7, Micha Sam B Raredon 2 7, Jake Dengelegi 8, Kun-Yong Kim 1, Pingnan Sun 1, Mei Zhong 9, Sangho Lee 10, Prabir Patra 1 8, Fahmeed Hyder 3 7, Laura E Niklason 2 7, Sang-Hun Lee 4 5, Young-Sup Yoon 10 11, In-Hyun Park 12Affiliations expand PMID: 31591580 PMCID: PMC6918722 DOI: 10.1038/s41592-019-0586-5 Abstract Human cortical organoids (hCOs), derived from human […]

Human pluripotent stem cell (hPSC)-derived endothelial cells (ECs) have limited clinical utility because of undefined components in the differentiation system and poor cell survival in vivo. Here, we aimed to develop a fully defined and clinically compatible system to differentiate hPSCs into ECs. Furthermore, we aimed to enhance cell survival, vessel formation, and therapeutic potential by encapsulating hPSC-ECs with a peptide amphiphile (PA) nanomatrix gel. We induced differentiation of hPSCs into the mesodermal lineage by culturing on collagen-coated plates with a glycogen synthase kinase 3β inhibitor. Next, vascular endothelial growth factor, endothelial growth factor, and basic fibroblast growth factor were added for endothelial lineage differentiation, followed by sorting for CDH5 (VE-cadherin). We constructed an extracellular matrix-mimicking PA nanomatrix gel (PA-RGDS) by incorporating the cell adhesive ligand Arg-Gly-Asp-Ser (RGDS) and a matrix metalloproteinase-2-degradable sequence. We then evaluated whether the encapsulation of hPSC-CDH5+ cells in PA-RGDS could enhance long-term cell survival and vascular regenerative effects in a hind-limb ischemia model with laser Doppler perfusion imaging, bioluminescence imaging, real-time reverse transcription-polymerase chain reaction, and histological analysis. The resultant hPSC-derived CDH5+ cells (hPSC-ECs) showed highly enriched and genuine EC characteristics and proangiogenic activities. When injected into ischemic hind limbs, hPSC-ECs showed better perfusion recovery and higher vessel-forming capacity compared with media-, PA-RGDS-, or human umbilical vein EC-injected groups. However, the group receiving the PA-RGDS-encapsulated hPSC-ECs showed better perfusion recovery, more robust and longer cell survival (> 10 months), and higher and prolonged angiogenic and vascular incorporation capabilities than the bare hPSC-EC-injected group. Surprisingly, the engrafted hPSC-ECs demonstrated previously unknown sustained and dynamic vessel-forming behavior: initial perivascular concentration, a guiding role for new vessel formation, and progressive incorporation into the vessels over 10 months. We generated highly enriched hPSC-ECs via a clinically compatible system. Furthermore, this study demonstrated that a biocompatible PA-RGDS nanomatrix gel substantially improved long-term survival of hPSC-ECs in an ischemic environment and improved neovascularization effects of hPSC-ECs via prolonged and unique angiogenic and vessel-forming properties. This PA-RGDS-mediated transplantation of hPSC-ECs can serve as a novel platform for cell-based therapy and investigation of long-term behavior of hPSC-ECs.

Transplantations of various stem cells or their progeny have repeatedly improved cardiac performance in animal models of myocardial injury; however, the benefits observed in clinical trials have been generally less consistent. Some of the recognized challenges are poor engraftment of implanted cells and, in the case of human cardiomyocytes, functional immaturity and lack of electrical integration, leading to limited contribution to the heart’s contractile activity and increased arrhythmogenic risks. Advances in tissue and genetic engineering techniques are expected to improve the survival and integration of transplanted cells, and to support structural, functional, and bioenergetic recovery of the recipient hearts. Specifically, application of a prefabricated cardiac tissue patch to prevent dilation and to improve pumping efficiency of the infarcted heart offers a promising strategy for making stem cell therapy a clinical reality.