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
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.045 | 0.077 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.026 | 0.054 |
| Bibliometrics | 0.006 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".