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Abstract
Mesenchymal stem cell (MSC)-based therapy has emerged as a promising regenerative therapeutic approach for wound healing. To determine the effects of cultured MSCs as a 2D monolayer (2D-MSCs) and 3D spheroids (3D-MSCs) on their secretomes, and to examine the effect of 3D-MSC secretomes on endothelial cells (ECs) and MSCs in a burn injury mouse model. MSCs were cultured as 2D monolayers (2D-MSCs) and 3D spheroids (3D-MSCs) and their cellular characteristics were evaluated by western blotting. 2D-MSC and 3D-MSC secretomes (condition medium: CM) were analyzed using an angiogenic array. The activation of ECs by 2D-MSC and 3D-MSC CMs was examined in cellular proliferation, migration, and tube formation assays. The wound healing effects of 2D-MSCs and 3D-MSCs were determined in vivo using a burn injury mouse model. 3D culture conditions altered the markers of components that regulate cell survival, cytoskeletal, adhesion, and proliferation. Interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA), IL-8, and chemokine (CXC motif) ligand 1 (CXCL1) were present at high levels in the CM of 3D-MSCs compared with 2D-MCs. 3D-MSC-CMs promoted the proliferation, migration, and tube formation of ECs. Furthermore, 3D-MSC treatment enhanced wound healing in a burn injury mouse model. 3D culture improves proangiogenic factors in the MSC secretome and 3D-MSCs represent a new cell-based treatment strategy for wound healing.

Affiliations

Prakash Gangadaran 1, Eun Jung Oh 2, Ramya Lakshmi Rajendran 3, Ji Min Oh 3, Hyun Mi Kim 2, Suin Kwak 4, Ho Yun Chung 4, Jaetae Lee 5, Byeong-Cheol Ahn 6, Chae Moon Hong 7
1BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, 41944, South Korea; Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, South Korea.
2Department of Plastic and Reconstructive Surgery, CMRI, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, South Korea.
3Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, South Korea.
4BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, 41944, South Korea; Department of Plastic and Reconstructive Surgery, CMRI, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, South Korea.
5Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, South Korea; Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, 41944, South Korea.
6BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, 41944, South Korea; Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, South Korea; Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, 41944, South Korea. Electronic address: abc2000@knu.ac.kr.
7Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, South Korea; Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, 41944, South Korea. Electronic address: cmhong@knu.ac.kr.