{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:39:59Z","timestamp":1760060399112,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation (NRF) of Korea grants funded by the Korean Government","award":["NRF-2022R1F1A1064405","NRF-2022R1F1A1068778"],"award-info":[{"award-number":["NRF-2022R1F1A1064405","NRF-2022R1F1A1068778"]}]},{"name":"Catholic Kwandong University International St. Mary\u2019s Hospital for S.-W Kim and the NRF of Korea grant funded by the Korean government","award":["NRF-2022R1F1A1064405","NRF-2022R1F1A1068778"],"award-info":[{"award-number":["NRF-2022R1F1A1064405","NRF-2022R1F1A1068778"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adipose-derived mesenchymal stem cells (ASCs) have great potential in regenerative medicine due to their abundance and innate multi-lineage differentiation potential. However, the therapeutic efficacy of ASCs is often compromised by poor microenvironmental conditions in the damaged tissues after transplantation. In this study, we generated and assessed genetically modified ASCs that expressed granulocyte chemotactic protein-2 (GCP-2) and platelet-derived growth factor-\u03b2 (PDGF-\u03b2). The results revealed that three-dimensional (3D)-cultured ASCs overexpressing GCP-2 and PDGF-\u03b2 (3D-A\/GP) yielded a significant increase in proangiogenic gene expression, cell migration, and endothelial tube formation in vitro. Moreover, the Matrigel plug assay revealed that 3D-A\/GP formed functional blood vessels, and 3D-A\/GP injection in a hind limb ischemia (HLI) model revealed higher blood flow recovery, limb salvage, and capillary density and lower apoptosis in mice, compared to the controls. Notably, 3D-A\/GP exhibited differentiation into endothelial-like cells and upregulated expression of angiogenic factors in ischemic limb tissue. Our results highlight the value of using a combination of genetic engineering and 3D culture systems to improve the therapeutic effect of ASCs in terms of angiogenesis-dependent tissue repair. The dual modulation of GCP-2 and PDGF-\u03b2, in combination with 3D culture, presents a new and synergistic opportunity to maximize the use of ASC-based therapies for ischemic diseases and other regenerative medicine applications.<\/jats:p>","DOI":"10.3390\/ijms26178425","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T16:42:21Z","timestamp":1756485741000},"page":"8425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Robust Angio-Vasculogenic Properties of 3D-Cultured Dual GCP-2\/PDGF-\u03b2 Gene-Edited Human ASCs"],"prefix":"10.3390","volume":"26","author":[{"given":"Seongho","family":"Han","sequence":"first","affiliation":[{"name":"Department of Family Medicine, College of Medicine, Dong-A University, Busan 49236, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6022-6058","authenticated-orcid":false,"given":"Sang Joon","family":"An","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Catholic Kwandong University, International St. Mary\u2019s Hospital, Incheon 22711, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Whan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, Catholic Kwandong University, Gangneung 210-701, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1089\/107632701300062859","article-title":"Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies","volume":"7","author":"Zuk","year":"2001","journal-title":"Tissue Eng."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1161\/01.RES.0000265074.83288.09","article-title":"Adipose-Derived Stem Cells for Regenerative Medicine","volume":"100","author":"Gimble","year":"2007","journal-title":"Circ. 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