Effect of stem cell therapies on tendon-bone healing after anterior cruciate ligament reconstruction in animal models: a systematic review and meta-analysis
- 1Department of Joint Surgery, Weifang People’s Hospital, Shandong Second Medical University Weifang , , ,
Abstract
Background: Poor tendon-bone healing is a major contributor to graft failure after anterior cruciate ligament (ACL) reconstruction. Stem cell-based approaches, including mesenchymal stem cells (MSCs) and their derivatives, have shown promise in animal models, but findings remain heterogeneous.
Methods: PubMed, Embase, Scopus, SPORTDiscus, and the Cochrane Library were systematically searched from inception to December 2025 for controlled animal studies evaluating stem cell-based interventions in ACL reconstruction. Outcomes included biomechanical properties (ultimate failure load and stiffness), bone volume fraction (BV/TV) assessed by micro-CT, and histological integration. Risk of bias was assessed using SYRCLE’s tool. Pooled standardized mean differences (SMDs) were calculated using random-effects models.
Results: Sixteen controlled animal studies were included, involving diverse stem cell types, including bone marrow-derived mesenchymal stem cells (BMSCs), adipose-derived stem cells (ADSCs), tendon-derived stem cells (TDSCs), and synovium-derived mesenchymal stem cells (SMSCs), as well as different delivery strategies. Compared with controls, stem cell-based interventions significantly improved tendon-bone healing outcomes, including ultimate failure load (SMD = 1.34, 95% CI 0.93–1.75), stiffness (SMD = 0.96, 95% CI 0.64–1.27), BV/TV (SMD = 1.03, 95% CI 0.75–1.31), and histological integration (SMD = 0.86, 95% CI 0.59–1.13), all P < 0.00001. Substantial heterogeneity was observed across outcomes, and the overall risk of bias was moderate, reflecting variability in animal species, cell sources, delivery methods, and follow-up durations.
Conclusion: In animal models of ACL reconstruction, stem cell-based therapies significantly improve biomechanical properties, including ultimate failure load and stiffness, as well as bone formation and histological integration. The most pronounced effects were observed during the early healing phase, particularly at 4–6 weeks. Standardized preclinical protocols and longer-term evaluations are needed before clinical translation.
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BibTeX
@article{sun2026effect,
title = {{Effect of stem cell therapies on tendon-bone healing after anterior cruciate ligament reconstruction in animal models: a systematic review and meta-analysis}},
author = {Xuedong Sun and Shibo Zhao and Congcong Wang},
journal = {Frontiers in bioengineering and biotechnology},
year = {2026},
month = oct,
doi = {10.3389/fbioe.2026.1869863},
url = {https://europepmc.org/article/PMC/PMC13728609},
note = {CC BY},
}
RIS
TY - JOUR
TI - Effect of stem cell therapies on tendon-bone healing after anterior cruciate ligament reconstruction in animal models: a systematic review and meta-analysis
AU - Xuedong Sun
AU - Shibo Zhao
AU - Congcong Wang
PY - 2026
DA - 2026/10/20
JO - Frontiers in bioengineering and biotechnology
DO - 10.3389/fbioe.2026.1869863
UR - https://europepmc.org/article/PMC/PMC13728609
AB - Background: Poor tendon-bone healing is a major contributor to graft failure after anterior cruciate ligament (ACL) reconstruction. Stem cell-based approaches, including mesenchymal stem cells (MSCs) and their derivatives, have shown promise in animal models, but findings remain heterogeneous. Methods: PubMed, Embase, Scopus, SPORTDiscus, and the Cochrane Library were systematically searched from inception to December 2025 for controlled animal studies evaluating stem cell-based interventions in ACL reconstruction. Outcomes included biomechanical properties (ultimate failure load and stiffness), bone volume fraction (BV/TV) assessed by micro-CT, and histological integration. Risk of bias was assessed using SYRCLE’s tool. Pooled standardized mean differences (SMDs) were calculated using random-effects models. Results: Sixteen controlled animal studies were included, involving diverse stem cell types, including bone marrow-derived mesenchymal stem cells (BMSCs), adipose-derived stem cells (ADSCs), tendon-derived stem cells (TDSCs), and synovium-derived mesenchymal stem cells (SMSCs), as well as different delivery strategies. Compared with controls, stem cell-based interventions significantly improved tendon-bone healing outcomes, including ultimate failure load (SMD = 1.34, 95% CI 0.93–1.75), stiffness (SMD = 0.96, 95% CI 0.64–1.27), BV/TV (SMD = 1.03, 95% CI 0.75–1.31), and histological integration (SMD = 0.86, 95% CI 0.59–1.13), all P < 0.00001. Substantial heterogeneity was observed across outcomes, and the overall risk of bias was moderate, reflecting variability in animal species, cell sources, delivery methods, and follow-up durations. Conclusion: In animal models of ACL reconstruction, stem cell-based therapies significantly improve biomechanical properties, including ultimate failure load and stiffness, as well as bone formation and histological integration. The most pronounced effects were observed during the early healing phase, particularly at 4–6 weeks. Standardized preclinical protocols and longer-term evaluations are needed before clinical translation.
SN - 2296-4185
ER -