2017 ISAKOS Biennial Congress ePoster #1148

 

Multipotent Cells Used in Anterior Cruciate Ligament Surgery: A Systematic Review Of Animal and Clinical Trials

Bin Xu, MD, Hefei CHINA
Ruipeng Guo, PhD, Hannover GERMANY
Liang Gao, MD, PhD, Msc, MBBS, Homburg GERMANY
Honggang Xu, Hefei, Anhui CHINA
Jun Tu, MS, HeFei, AnHui CHINA

Department of Sports Medicine and Arthroscopic Surgery, The First Affiliated Hospital of Anhui Medical University, hefei, CHINA

FDA Status Not Applicable

Summary

This study systematically reviewed the best current evidence of using multipotent cells as a biological augmentation in ACL surgery and concluded its efficacy in animal and clinical models.

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Abstract

Purpose

To enhance graft healing in both articular cavity and bone tunnel in anterior cruciate ligament (ACL) surgery, tissue-engineering approaches showed promising results in terms of enhancement of graft maturation and tendon-bone integration. The aim of this present study is to systematically review the best current evidence of using multipotent cells as a biological augmentation in ACL surgery and to conclude its efficacy in animal and clinical studies.

Methods

A comprehensive literature search was conducted for all relevant articles using the electronic databases Pubmed (Medline), Embase and Medline (using OvidSP) on November 16, 2016. The inclusion criteria were in vivo studies concerning the usage of multipotent cells in clinical patients and animal models of ACL reconstruction or repair with a control group. Terms including stem cells, stromal cells, progenitor cells, bone marrow and anterior cruciate ligament were used.

Results

After applying inclusion criteria and exclusion criteria on full text, 15 studies (2 clinical study and 13 animal studies) were included in final review, which were published between 2004 and 2015. In methodological quality assessment, only 6 animal studies scored 5 or higher were appraised with satisfactory study quality. Among the included preclinical studies, 12 studies utilized small animals (rabbit and rat) to create injury model of ACL and large animal model (dog) was used in only one study. ACL reconstruction was carried out in 11 occasions and ACL transection and repair was performed in 2 articles. Concerning the graft source in ACL reconstruction, allograft was used in 2/11 and autograft in 9/11.

Five different types of multipotent stem cells were isolated from different sources in animal studies: bone marrow derived-mesenchymal stem (stromal) cells (BMSCs), whole bone marrow cells (BMCs), ACL-derived CD34+ cell, tendon-derived stem cells (TDSCs) and human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). For included clinical studies, non-cultured BMSCs and novel Healing Response Treatment(HRT) were utilized.

Positive prompting effect of different multipotent stem cells in tendon maturation or tendon-bone healing was reported in 12 animal studies, and the only animal research showing negative result was BMSCs in autograft ACL reconstruction of rabbits, using a novel surgical technique. Of note, the follow-up time in most animal trials was no more than 8 weeks. Interestingly, no enhancement of graft healing and knee function after surgery was demonstrated by both clinical trials

Conclusions

This system review reviewing multipotent cells in ACL surgery concluded that there is sufficient evidence in small animal trials proving that BMSCs and ACL-derived vascular stem cells possess promotable effect in ACL healing. TDSCs and hUCB–MSCs might potentially be alternative cell types. Further research should testify these conclusions in large animal and clinical trials.