Efficient expansion and delayed senescence of hUC-MSCs by microcarrier–bioreactor system

Stem Cell Research & Therapy

Research

Yulin Cao¹  Lixin Zhang²  Liming Ouyang²  Wenxia Chen²  Xia Wang² 

[1] Beijing Tang Yi Hui Kang Biomedical Technology Co., LTD, 100032, Beijing, People’s Republic of China;State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 200237, Shanghai, People’s Republic of China;

关键词: Human umbilical cord mesenchymal stem cells;    Microcarrier;    Transcriptome;    Cell senescence;    Bioreactor;    Cell culture;   

DOI  :  10.1186/s13287-023-03514-1

 received in 2023-06-06, accepted in 2023-09-25,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundHuman 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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