PMID- 37794520 OWN - NLM STAT- MEDLINE DCOM- 20231006 LR - 20231122 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 14 IP - 1 DP - 2023 Oct 4 TI - Efficient expansion and delayed senescence of hUC-MSCs by microcarrier-bioreactor system. PG - 284 LID - 10.1186/s13287-023-03514-1 [doi] LID - 284 AB - BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) are widely used in cell therapy due to their robust immunomodulatory and tissue regenerative capabilities. Currently, the predominant method for obtaining hUC-MSCs for clinical use is through planar culture expansion, which presents several limitations. Specifically, continuous cell passaging can lead to cellular aging, susceptibility to contamination, and an absence of process monitoring and control, among other limitations. To overcome these challenges, the technology of microcarrier-bioreactor culture was developed with the aim of ensuring the therapeutic efficacy of cells while enabling large-scale expansion to meet clinical requirements. However, there is still a knowledge gap regarding the comparison of biological differences in cells obtained through different culture methods. METHODS: We developed a culture process for hUC-MSCs using self-made microcarrier and stirred bioreactor. This study systematically compares the biological properties of hUC-MSCs amplified through planar culture and microcarrier-bioreactor systems. Additionally, RNA-seq was employed to compare the differences in gene expression profiles between the two cultures, facilitating the identification of pathways and genes associated with cell aging. RESULTS: The findings revealed that hUC-MSCs expanded on microcarriers exhibited a lower degree of cellular aging compared to those expanded through planar culture. Additionally, these microcarrier-expanded hUC-MSCs showed an enhanced proliferation capacity and a reduced number of cells in the cell cycle retardation period. Moreover, bioreactor-cultured cells differ significantly from planar cultures in the expression of genes associated with the cytoskeleton and extracellular matrix. CONCLUSIONS: The results of this study demonstrate that our microcarrier-bioreactor culture method enhances the proliferation efficiency of hUC-MSCs. Moreover, this culture method exhibits the potential to delay the process of cell aging while preserving the essential stem cell properties of hUC-MSCs. CI - (c) 2023. BioMed Central Ltd., part of Springer Nature. FAU - Wang, Xia AU - Wang X AD - State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China. FAU - Ouyang, Liming AU - Ouyang L AUID- ORCID: 0000-0003-3507-7895 AD - State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China. ouyanglm@ecust.edu.cn. FAU - Chen, Wenxia AU - Chen W AD - State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China. FAU - Cao, Yulin AU - Cao Y AD - Beijing Tang Yi Hui Kang Biomedical Technology Co., LTD, Beijing, 100032, People's Republic of China. FAU - Zhang, Lixin AU - Zhang L AD - State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231004 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 SB - IM MH - Humans MH - *Mesenchymal Stem Cells/metabolism MH - Cells, Cultured MH - Cellular Senescence MH - Stem Cells MH - Bioreactors MH - Umbilical Cord MH - Cell Differentiation MH - *Mesenchymal Stem Cell Transplantation PMC - PMC10552362 OTO - NOTNLM OT - Bioreactor OT - Cell culture OT - Cell senescence OT - Human umbilical cord mesenchymal stem cells OT - Microcarrier OT - Transcriptome COIS- Corresponding author Liming Ouyang has received research grants from Beijing Tang Yi Hui Kang Biomedical Technology Co., Ltd. Author Yulin Cao is a senior executive at Beijing Tang Yi Hui Kang Biomedical Technology Co., Ltd., that has invested in the research and holds shares in the company. The other authors declare no competing interests. EDAT- 2023/10/05 01:00 MHDA- 2023/10/06 06:43 PMCR- 2023/10/04 CRDT- 2023/10/04 23:50 PHST- 2023/06/06 00:00 [received] PHST- 2023/09/25 00:00 [accepted] PHST- 2023/10/06 06:43 [medline] PHST- 2023/10/05 01:00 [pubmed] PHST- 2023/10/04 23:50 [entrez] PHST- 2023/10/04 00:00 [pmc-release] AID - 10.1186/s13287-023-03514-1 [pii] AID - 3514 [pii] AID - 10.1186/s13287-023-03514-1 [doi] PST - epublish SO - Stem Cell Res Ther. 2023 Oct 4;14(1):284. doi: 10.1186/s13287-023-03514-1.