Current Evidence of Adult Stem Cells to Enhance Anterior Cruciate Ligament Treatment: A Systematic Review of Animal Trials.

Purpose: To systematically review the available preclinical evidence of adult stem cells as a biological augmentation in the treatment of animal anterior cruciate ligament (ACL) injury. Study

Design: Systematic review.

Methods: PubMed (MEDLINE) and Embase were searched for the eligible studies. The inclusion criteria were controlled animal trials of adult stem cells used in ACL treatment (repair or reconstruction). Studies of natural ACL healing without intervention, in vitro studies, ex vivo studies, and studies without controls were excluded. Evidence level, methodologic quality, and risk of bias of each included study were identified using previously established tools.

Results: Thirteen animal studies were included. Six of 7 studies using bone marrow-derived mesenchymal stem (stromal) cells (BMSCs) reported a positive enhancement in histology, biomechanics, and biochemistry within 12 weeks postoperatively. Four studies using ACL-derived vascular stem cells showed a promoting effect in histology, biomechanics, and imaging within 8 weeks postoperatively. Two studies focusing on animal tendon-derived stem cells (TDSCs) and human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) reported promotable effects for the early healing in a small animal ACL model.

Conclusions: BMSCs, ACL-derived vascular stem cells, TDSCs, and hUCB-MSCs were shown to enhance the healing of ACL injury during the early phase in small animal models. Clinical relevance: Results of clinical trials using adult stem cells in ACL treatment are conflicting, and a systematic review of the current best preclinical evidence is crucial to guide further application.