Safety of Intravascular Administration of Umbilical-cord Derived Mesenchymal Stromal Cells: An Updated Systematic Review and Meta-analysis
Bibliographic record
Abstract
Abstract Rationale: Mesenchymal stem cells (MSCs), in particular umbilical cord-derived MSCs (UC-MSCs), have the capacity to self-renew and exert immunomodulatory and paracrine effects. Our previously published safety systematic review of 55 randomized controlled trials (RCTs), which included 16 trials with UC MSCs, found that MSCs demonstrated a favourable safety profile, with the exception of fever that was more frequent for the MSC as compared to the control group. Our team is conducting a Phase II RCT of UC-MSC therapy in septic shock. Hence, we sought to evaluate and update the safety profile of UC-MSC therapy specifically as several more UC-MSC RCTs have been published since our previous review in 2019. Methods: We conducted a systematic search on Embase, Ovid MEDLINE, and Cochrane Central Register of Controlled Trials up to April 15, 2024. RCTs that compared intravascular delivery of UC-MSCs (intravenously or intra-arterially) in adult populations compared to a control group that did not receive UC-MSCs were identified. The primary outcome was categorized based on the following pre-specified adverse events: (1) fever within 24 h of drug administration, (2) non-fever acute infusional toxicity within 24 h of drug administration, (3) infection, (4) death, (5) malignancy/ectopic tissue formation, (6) thrombo-embolic events, and (7) mycotic aneurysms. Pre-specified adverse events were pooled and meta-analyzed by fitting inverse-variance binary random effects models where appropriate. Results: A total of 8094 studies were screened and 37 studies met eligibility criteria (n=1980 patients). The studies included a diverse patient population with a wide range of conditions, including cardiovascular (n=3), neurological (n=1), oncological/hematological (n=3), endocrine diseases (n=4), renal (n=1), hepatic (n=3), respiratory (n=16), and immune-deficient or inflammatory disorders (n=6). No significant safety signals were found for UC-MSCs as compared to controls for any prespecified adverse events (fever (relative risk (RR)= 1.60, 95% Confidence Interval (CI)= 0.90-2.86), non-fever acute infusional toxicity (RR= 1.04, 95% CI = 0.71-1.52), infection (RR= 0.78, 95% CI= 0.43-1.40), death (RR= 0.88, 95% CI= 0.72-1.08), thrombo-embolic event (RR= 0.80, 95% CI= 0.47-1.36), aneurysms (RR= 0.94, CI= 0.72-1.22) or malignancy (RR= 0.79, 95% CI= 0.64-0.98)). No included trials ended early due to safety concerns. Conclusion: UC-MSC therapy continues to appear safe for study in heterogeneous patient populations.
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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 | 0.011 | 0.036 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.015 | 0.021 |
| Bibliometrics | 0.008 | 0.008 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| 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".