1. Enhancement of anti-inflammatory and immunomodulatory effects of adipose-derived human mesenchymal stem cells by making uniform spheroid on the new nano-patterned plates.
- Author
-
Lee S, Kim HS, Min BH, Kim BG, Kim SA, Nam H, Lee M, Kim M, Hwang HY, Leesong AI, Leesong MM, Kim JH, and Shin JS
- Subjects
- Animals, Cell Culture Techniques instrumentation, Cells, Cultured, Diabetes Mellitus, Experimental immunology, Diabetes Mellitus, Experimental therapy, Gene Expression immunology, Humans, Male, Mesenchymal Stem Cell Transplantation methods, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells metabolism, Mice, Inbred C57BL, Spheroids, Cellular metabolism, Transcription Factors genetics, Transcription Factors immunology, Transcription Factors metabolism, Mice, Adipose Tissue cytology, Anti-Inflammatory Agents immunology, Cell Culture Techniques methods, Immunologic Factors immunology, Mesenchymal Stem Cells immunology, Spheroids, Cellular immunology
- Abstract
Human mesenchymal stem cells (MSCs) are known to have anti-inflammatory and immunomodulatory functions; thus, several MSC products have been applied as cell therapy in clinical trials worldwide. Recent studies have demonstrated that MSC spheroids have superior anti-inflammatory and immunomodulatory functions to a single cell suspension. Current methods to prepare MSC spheroids include hanging drop, concave microwell aggregation, spinner flask, and gravity circulation. However, all these methods have limitations such as low scalability, easy cell clumping, low viability, and irregular size distribution. Here, we present a nano-patterned culture plasticware named PAMcell™ 3D plate to overcome these limitations. Nano-sized silica particles (700 nm) coated with RGD peptide were arrayed into fusiform onto the PLGA film. This uniform array enabled the seeded MSCs to grow only on the silica particles, forming uniform-sized semi-spheroids within 48 h. These MSC spheroids have been shown to have enhanced stemness, anti-inflammatory, and immunomodulatory functions, as revealed by the increased expression of stem cell markers (Oct4, Sox2, and Nanog), anti-inflammatory (IL-10, TSG6, and IDO), and immunomodulatory molecules (HGF, VEGF, CXCR4) both at mRNA and protein expression levels. Furthermore, these MSC spheroids demonstrated an increased palliative effect on glycemic control in a multiple low-dose streptozotocin-induced diabetes model compared with the same number of MSC single cell suspensions. Taken together, this study presents a new method to produce uniform-sized MSC spheroids with enhanced anti-inflammatory and immunomodulatory functions in vitro and in vivo., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF