Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cells

Bibliographic Details
Title: Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cells
Authors: Qi-Ming Huang, You-Qiong Zhuo, Zhong-Xin Duan, Yin-lin Long, Jia-Nan Wang, Zhou-hang Zhang, Shao-Yong Fan, Yong-Ming Huang, Ke-Yu Deng, Hong-Bo Xin
Source: Bone & Joint Research, Vol 13, Iss 12, Pp 764-778 (2024)
Publisher Information: The British Editorial Society of Bone & Joint Surgery, 2024.
Publication Year: 2024
Collection: LCC:Diseases of the musculoskeletal system
Subject Terms: mesenchymal stem cells, hypoxia, osteoarthritis, mesenchymal stem cells (mscs), chondrocytes, mice model, transplantations, mmp-13, apoptosis, osteoarthritis (oa), cartilage damage, swelling, Diseases of the musculoskeletal system, RC925-935
More Details: Aims: Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application. Methods: In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II. Results: We observed that long-term hypoxic culture surpassed normoxic atmosphere during hUC-MSCs culture in respect of promoting proliferation, anti-tumorigenicity, maintaining normal karyotype and stemness, inhibiting senescence, and improving immunoregulatory function and the role of anti-apoptosis in chondrocytes. Furthermore, we demonstrated that the transplantation of long-term hypoxic hUC-MSCs (Hy-MSCs) had a better therapeutic effect on OA rats compared with the hUC-MSCs cultured in the normoxic atmosphere (No-MSCs) in terms of the improved function and swelling recovery in the joints, and substantially inhibited the secretion of pro-inflammatory factors, which effectively alleviated cartilage damage by reducing the expression of matrix metallopeptidase 13 (MMP-13). Conclusion: Our results demonstrate that Hy-MSCs possess immense potential for clinical applications via promoting stemness maintenance and enhancing immunoregulatory function. Cite this article: Bone Joint Res 2024;13(12):763–777.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2046-3758
Relation: https://doaj.org/toc/2046-3758
DOI: 10.1302/2046-3758.1312.BJR-2024-0136.R2
Access URL: https://doaj.org/article/f441f8a927c148caad96beb005ed96a6
Accession Number: edsdoj.f441f8a927c148caad96beb005ed96a6
Database: Directory of Open Access Journals
More Details
ISSN:20463758
DOI:10.1302/2046-3758.1312.BJR-2024-0136.R2
Published in:Bone & Joint Research
Language:English