Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cells
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 tra...
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The British Editorial Society of Bone & Joint Surgery
2024-12-01
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| Series: | Bone & Joint Research |
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| Online Access: | https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.1312.BJR-2024-0136.R2 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Qi-Ming Huang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f441f8a927c148caad96beb005ed96a6 |
| institution | Kabale University |
| issn | 2046-3758 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | The British Editorial Society of Bone & Joint Surgery |
| record_format | Article |
| series | Bone & Joint Research |
| spelling | doaj-art-f441f8a927c148caad96beb005ed96a62025-01-28T06:54:06ZengThe British Editorial Society of Bone & Joint SurgeryBone & Joint Research2046-37582024-12-01131276477810.1302/2046-3758.1312.BJR-2024-0136.R2Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cellsQi-Ming Huang0https://orcid.org/0000-0001-8894-5444You-Qiong Zhuo1https://orcid.org/0009-0009-4780-2637Zhong-Xin Duan2https://orcid.org/0009-0003-8569-9331Yin-lin Long3https://orcid.org/0009-0006-5724-469XJia-Nan Wang4https://orcid.org/0009-0001-5932-2608Zhou-hang Zhang5https://orcid.org/0009-0004-7811-5067Shao-Yong Fan6https://orcid.org/0000-0001-8832-5499Yong-Ming Huang7https://orcid.org/0000-0002-4563-8652Ke-Yu Deng8Hong-Bo Xin9https://orcid.org/0000-0003-4360-2995The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, ChinaThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, ChinaLushan Botanical Garden, Jiangxi Province and Chinese Academy of Sciences, Lushan, ChinaThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, ChinaThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, ChinaThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, ChinaSports Medicine Department, Hongdu Traditional Chinese Medicine Hospital, Nanchang, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, ChinaThe National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, ChinaAims: 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.https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.1312.BJR-2024-0136.R2mesenchymal stem cellshypoxiaosteoarthritismesenchymal stem cells (mscs)chondrocytesmice modeltransplantationshypoxiammp-13apoptosisosteoarthritis (oa)cartilage damageswelling |
| spellingShingle | 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 Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cells Bone & Joint Research mesenchymal stem cells hypoxia osteoarthritis mesenchymal stem cells (mscs) chondrocytes mice model transplantations hypoxia mmp-13 apoptosis osteoarthritis (oa) cartilage damage swelling |
| title | Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cells |
| title_full | Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cells |
| title_fullStr | Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cells |
| title_full_unstemmed | Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cells |
| title_short | Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cells |
| title_sort | long term hypoxic atmosphere enhances the stemness immunoregulatory functions and therapeutic application of human umbilical cord mesenchymal stem cells |
| topic | mesenchymal stem cells hypoxia osteoarthritis mesenchymal stem cells (mscs) chondrocytes mice model transplantations hypoxia mmp-13 apoptosis osteoarthritis (oa) cartilage damage swelling |
| url | https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.1312.BJR-2024-0136.R2 |
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