PMID- 37697417 OWN - NLM STAT- MEDLINE DCOM- 20230913 LR - 20231121 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 14 IP - 1 DP - 2023 Sep 12 TI - What is the optimal dose of adipose-derived mesenchymal stem cells treatment for knee osteoarthritis? A conventional and network meta-analysis of randomized controlled trials. PG - 245 LID - 10.1186/s13287-023-03475-5 [doi] LID - 245 AB - BACKGROUND: Despite increasing clinical investigations underscoring the efficacy and safety of adipose-derived mesenchymal stem cells (AD-MSCs) therapy in knee osteoarthritis (KOA), no article has recently reviewed the cell dosage. This study aimed to evaluate the efficacy and safety of varying doses of AD-MSCs in treating KOA using conventional and network meta-analysis. METHODS: A search of databases in in Chinese and English was performed to identify randomized controlled trials (RCT) on MSCs for knee osteoarthritis from the inception date to May 1, 2022. This study mainly analyzed the efficacy of AD-MSCs in the treatment of KOA, and subgroup analysis was performed on the therapeutic effects of MSCs from different tissues at the same dose. We divided the different cell doses into low, moderate, and high groups, with the corresponding cell doses: (0-25)*10;6, (25-50)*10;6, and > 50*10;6 cells, respectively. We further analyzed the improvement of improvement of the Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores and the incidence of adverse events (AEs) after varied dosage injection. RESULTS: A total of 16 literatures were included in this study, of which 8 literatures were about AD-MSCs. Conventional meta-analysis suggests that AD-MSCs can reduce pain and improve function in KOA patients, regardless of the cell doses, up to 12 months of follow-up. The network meta-analysis showed that intra-articular injection of AD-MSCs significantly improved pain and knee function scores in KOA patients compared with the control group at 3, 6, and 12 months. Among the three groups, the high-dose group had the best treatment effect, and the degree of joint pain and dysfunction indicators improved more significantly in the early stage. For adverse events, there was a dose-response trend that increased with increasing doses. CONCLUSIONS: Both cell doses reduced pain and improved knee function in KOA patients. The effect surpassed in the high-dose group than in the moderate-dose, low-dose and control groups. However, adverse events also increase with the increase in dose, which should be carefully considered in clinical application, and the side effects still need to be paid attention to. Considering the limitations of this meta-analysis, future studies need to further explore the efficacy and safety of different doses of treatment, and carry out large sample, multi-center, randomized controlled trials to ensure the reliability and promotion value of the research results. CI - (c) 2023. BioMed Central Ltd., part of Springer Nature. FAU - Huang, Zongyuan AU - Huang Z AD - Department of Orthopedics, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong Province, China. 424198470@qq.com. FAU - Zhang, Shuai AU - Zhang S AD - Department of Orthopedics, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong Province, China. FAU - Cao, Mingde AU - Cao M AD - Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. FAU - Lin, Zhujian AU - Lin Z AD - Department of Orthopedics, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong Province, China. FAU - Kong, Ling AU - Kong L AD - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China. FAU - Wu, Xin AU - Wu X AD - Department of Orthopedics, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong Province, China. FAU - Guo, Qianshi AU - Guo Q AD - Department of Orthopedics, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong Province, China. FAU - Ouyang, Yuxiang AU - Ouyang Y AD - Department of Orthopedics, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong Province, China. FAU - Song, Yancheng AU - Song Y AD - Department of Orthopedics, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong Pharmaceutical University, No. 19 Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong Province, China. hzyuan0626@163.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20230912 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 SB - IM MH - Humans MH - *Osteoarthritis, Knee/therapy MH - Network Meta-Analysis MH - Randomized Controlled Trials as Topic MH - Knee Joint MH - *Mesenchymal Stem Cells PMC - PMC10496179 OTO - NOTNLM OT - Cell doses OT - Knee osteoarthritis OT - Mesenchymal stem cells OT - Meta-analysis COIS- The authors declare that they have no competing interests. EDAT- 2023/09/12 06:42 MHDA- 2023/09/13 06:41 PMCR- 2023/09/12 CRDT- 2023/09/12 00:02 PHST- 2023/01/14 00:00 [received] PHST- 2023/08/25 00:00 [accepted] PHST- 2023/09/13 06:41 [medline] PHST- 2023/09/12 06:42 [pubmed] PHST- 2023/09/12 00:02 [entrez] PHST- 2023/09/12 00:00 [pmc-release] AID - 10.1186/s13287-023-03475-5 [pii] AID - 3475 [pii] AID - 10.1186/s13287-023-03475-5 [doi] PST - epublish SO - Stem Cell Res Ther. 2023 Sep 12;14(1):245. doi: 10.1186/s13287-023-03475-5.