Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence
Abstract Background Mesenchymal stem cells (MSCs) have been proposed to treat osteoarthritis (OA) for many years. However, clinical outcomes have been inconsistent due to biological variation between patients, differences in tissue source and preparation of the MSCs, and type of donor (e.g. allogeni...
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BMC
2024-11-01
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| Series: | Journal of Translational Medicine |
| Online Access: | https://doi.org/10.1186/s12967-024-05814-3 |
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| author | Houyi Sun Haoxin Zhai Kaifei Han Heran Ma Yi Tan Shihao Li Zhicheng Liu Lei Cheng Qunshan Lu Libo Zhou Peilai Liu |
| author_facet | Houyi Sun Haoxin Zhai Kaifei Han Heran Ma Yi Tan Shihao Li Zhicheng Liu Lei Cheng Qunshan Lu Libo Zhou Peilai Liu |
| author_sort | Houyi Sun |
| collection | DOAJ |
| description | Abstract Background Mesenchymal stem cells (MSCs) have been proposed to treat osteoarthritis (OA) for many years. However, clinical outcomes have been inconsistent due to biological variation between patients, differences in tissue source and preparation of the MSCs, and type of donor (e.g. allogenic versus autologous). Here, we test the hypothesis that inconsistent clinical outcomes are related to variations in the stemness and senescence of the injected autologous adipose-derived (AD) MSCs. Methods In the prospective randomized trial, 45 knee OA patients were divided into two groups: Group 1 (n = 22) patients treated with high tibial osteotomy (HTO) alone and Group 2 (n = 23) patients treated with HTO followed by intra-articular injection of autologous AD-MSCs (HTO + AD-MSCs). MRI and X-ray were performed pre-operation and 12 months post-operation. WOMAC and VAS score were collected four times, every 6 months over a 24-month follow-up. We observed the proliferation and stemness of AD-MSCs selected from the 5 patients showing the most improvement and from the 5 patients with the least improvement, and completed further in vitro experiments including beta-galactosidase activity, reactive oxygen species and bioinformatic analysis. Results The results showed that patients treated with HTO + AD-MSCs had a significant reduction in knee OA severity as compared to patients treated with HTO alone. Moreover, we discovered that proliferation and colony forming efficiency of AD-MSCs selected from the 5 patients showing the most improvement performed significantly better than cells selected from the 5 patients with the least improvement. AD-MSCs from the patients with the most improvement also had lower amounts of senescent cells and intracellular reactive oxygen species. Conclusions Clinical outcomes of autologous AD-MSCs therapy in knee osteoarthritis are correlated with stem cell stemness and senescence. Our study highlights emerging opportunities and trends in precision medicine that could potentially improve autologous MSC-based therapies. |
| format | Article |
| id | doaj-art-b839b0fcbe2447b4ab21b0bb46e30b54 |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-b839b0fcbe2447b4ab21b0bb46e30b542025-08-20T02:22:29ZengBMCJournal of Translational Medicine1479-58762024-11-0122111810.1186/s12967-024-05814-3Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescenceHouyi Sun0Haoxin Zhai1Kaifei Han2Heran Ma3Yi Tan4Shihao Li5Zhicheng Liu6Lei Cheng7Qunshan Lu8Libo Zhou9Peilai Liu10Department of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityQilu Cell Therapy Technology Co., LtdQilu Cell Therapy Technology Co., LtdDepartment of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong UniversityDepartment of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityAbstract Background Mesenchymal stem cells (MSCs) have been proposed to treat osteoarthritis (OA) for many years. However, clinical outcomes have been inconsistent due to biological variation between patients, differences in tissue source and preparation of the MSCs, and type of donor (e.g. allogenic versus autologous). Here, we test the hypothesis that inconsistent clinical outcomes are related to variations in the stemness and senescence of the injected autologous adipose-derived (AD) MSCs. Methods In the prospective randomized trial, 45 knee OA patients were divided into two groups: Group 1 (n = 22) patients treated with high tibial osteotomy (HTO) alone and Group 2 (n = 23) patients treated with HTO followed by intra-articular injection of autologous AD-MSCs (HTO + AD-MSCs). MRI and X-ray were performed pre-operation and 12 months post-operation. WOMAC and VAS score were collected four times, every 6 months over a 24-month follow-up. We observed the proliferation and stemness of AD-MSCs selected from the 5 patients showing the most improvement and from the 5 patients with the least improvement, and completed further in vitro experiments including beta-galactosidase activity, reactive oxygen species and bioinformatic analysis. Results The results showed that patients treated with HTO + AD-MSCs had a significant reduction in knee OA severity as compared to patients treated with HTO alone. Moreover, we discovered that proliferation and colony forming efficiency of AD-MSCs selected from the 5 patients showing the most improvement performed significantly better than cells selected from the 5 patients with the least improvement. AD-MSCs from the patients with the most improvement also had lower amounts of senescent cells and intracellular reactive oxygen species. Conclusions Clinical outcomes of autologous AD-MSCs therapy in knee osteoarthritis are correlated with stem cell stemness and senescence. Our study highlights emerging opportunities and trends in precision medicine that could potentially improve autologous MSC-based therapies.https://doi.org/10.1186/s12967-024-05814-3 |
| spellingShingle | Houyi Sun Haoxin Zhai Kaifei Han Heran Ma Yi Tan Shihao Li Zhicheng Liu Lei Cheng Qunshan Lu Libo Zhou Peilai Liu Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence Journal of Translational Medicine |
| title | Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence |
| title_full | Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence |
| title_fullStr | Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence |
| title_full_unstemmed | Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence |
| title_short | Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence |
| title_sort | clinical outcomes of autologous adipose derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence |
| url | https://doi.org/10.1186/s12967-024-05814-3 |
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