SLR - April 2016 - J. Adrian Wright
Reference: Goodrich LR, Chen AC, Werpy NM, Williams AA, Kisiday JD, Su AW, Cory E, Morley PS, McIIwraith CW, Sah RL, Chu CR. Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects: Does it Enhance Repair? J Bone Joint Surg Am. 2016. Jan 6; 98(1): 23-34.Scientific Literature Review
Reviewed By: J. Adrian Wright, DPM
Residency Program: Lenox Hill Hospital
Podiatric Relevance: The use of orthobiologics has become more prevalent over the past decade. Several compelling studies support the efficacy of these products for management of everything from wound care to cartilage replacement. With a focus on cartilage replacement, a recent interest regarding the use of culture-expanded bone-marrow-derived mesenchymal stem cells (BMDMSCs) has developed. Considerable data has been collected regarding the effects of growth factors from platelets, but a thorough investigation of the effects of stem cell application to an autologous platelet enriched fibrin (APEF) scaffold has yet to be investigated. Such novel studies are required prior to the use of human subjects. The data acquired from these approaches not only establishes the basis for further research, but possibly heralds the beginning of a paradigm shift in future treatment regimens.
Methods: Twelve horses (age range 2-5 years) with no past medical conditions were randomized into treatment (BMDMSCs + APEF) and control (APEF) groups within the double blinded study. A bone marrow aspiration from the ilium was performed four weeks prior to the arthroscopic creation of a 15mm defect in the lateral trochlear ridge of the femoropatellar joints. Depending on the random assignment of each subject, APEF, or APEF with BMDMSCs, was applied to the defect. Three months after the operation, arthroscopic assessment of the defects was performed and graded by surgeons blinded to the treatment groups. Additionally, an MRI was performed and scored by radiologists blinded to treatment groups utilizing a 20-point MRI scoring system for subchondral bone. Indentation testing to assess cartilage load bearing, quantitative MRI T2 mapping, micro-CT, and histological examination were also employed. An additional arthroscopic assessment was performed at 12 months. Results of individual analyses were quantified and compared using ANOVA and Wilcoxon signed rank with an alpha level of 0.05.
Results: The three month and twelve month arthroscopic assessments were compared between control and experimental groups utilizing the International Cartilage Repair Society (ICRS) scoring system. No significant difference was appreciated. Categorized and cumulative histological scoring between groups also revealed no significant difference in cartilage formation, however, bone formation was more pronounced in the APEF+BMBMSCs (experimental) group. MRI showed no statistically significant difference between the two groups with reference to cartilage, however, revealed a significantly greater amount of trabecular bone edema in the APEF+BMDMSCs group. MRI T2 mapping revealed development of bone like tissue in the repair zones, but no significant difference in soft tissue. Measurements of cartilaginous tissue revealed a diminished thickness in subjects treated with BMDMSCs as compared to those who were not.
Conclusion: APEF alone facilitates repair of chondral tissue, however, adding BMDMSCs to APEF does not improve this process. BMDMSCs may serve a role in stimulating bone formation. For this reason, future studies may elucidate a potential use of BMDMSCs with APEF in osteointegration.