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Treatment of Osteochondral Defects in the Rabbit's Knee Joint by Implantation of Allogeneic Mesenchymal Stem Cells in Fibrin Clots
Published on: May 21, 2013
Cell-Mediated Immune Responses May Play Roles in Osteochondral Allograft Transplantation Osteointegration Failures
Josephine Luk1, Chantelle C Bozynski1, Jonathan Williams1
1Department of Orthopaedic Surgery, Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri.
Abstract:
Prolonged and incomplete osteochondral allograft (OCA) osteointegration is consistently cited as a major mechanism for OCA treatment failure. Subrejection immune responses may play roles in this mode of failure. Preimplantation OCA preparation techniques, including subchondral bone drilling, thorough irrigation, and autogenous bone marrow aspirate concentrate saturation, may dampen immune responses and improve OCA osteointegration. This study sought to further characterize potential immune system contributions to OCA transplantation treatment failures by analyzing donor-recipient ABO and Rh-factor mismatches and histological and immunohistochemical assessments of transplanted OCA tissues recovered from revision surgeries. Using a dedicated registry, OCA transplant recipients with documented treatment failures who met inclusion criteria (n = 33) as well as age-, body mass index-, and joint-matched patients with successful outcomes (n = 70) were analyzed to compare matched cohorts of patients with successful versus failed OCA transplantation outcomes. Tissues recovered from 18 failed OCA transplants and portions of 7 nonimplanted OCA controls were further analyzed to provide contributing evidence for potential immune response mechanisms. For patients analyzed, no statistically significant differences in proportions for treatment success versus failure based on mismatches for ABO type, Rh factor, or both were noted. Further, no statistically significant differences in proportions for histological immune response presence or absence based on mismatches for ABO type, Rh factor, or both were noted. Twelve (67%) of the failed OCA tissues contained lymphocyte aggregations in the subchondral bone, which were comprised of combinations of CD3 + , CD4 + , CD8 + , and CD20+ lymphocytes. The mechanisms of failure for these 12 OCA transplants involved insufficient OCA osteointegration. Results of this study suggest that T- and B-cell-mediated subrejection immune responses may play roles in OCA transplant treatment failures independent of donor-recipient blood type mismatch effects.
Insights
Immune responses, not blood type, may cause osteochondral allograft (OCA) failure. Lymphocytes in failed grafts suggest T- and B-cell mediated subrejection responses contribute to poor osteointegration.
Area of Science:
- Orthopedic surgery
- Transplantation immunology
- Biomaterials science
Background:
- Osteochondral allograft (OCA) transplantation is a viable option for cartilage repair.
- Prolonged and incomplete osteointegration remains a significant cause of OCA treatment failure.
- Subrejection immune responses are hypothesized to contribute to OCA failure.
Purpose of the Study:
- To investigate the role of donor-recipient ABO and Rh-factor mismatches in OCA transplantation outcomes.
- To analyze the histological and immunohistochemical features of failed OCA tissues to identify immune-mediated mechanisms.
- To compare outcomes between successful and failed OCA transplant cohorts.
Main Methods:
- Retrospective analysis of OCA transplant recipients (33 failures, 70 successes) using a dedicated registry.
- Comparison of donor-recipient ABO and Rh-factor compatibility between failed and successful cohorts.
- Histological and immunohistochemical analysis of 18 failed OCA tissues and 7 controls for immune cell infiltration.
Main Results:
- No significant differences in treatment success or failure were observed based on ABO or Rh-factor mismatches.
- Histological immune responses did not correlate with ABO or Rh-factor mismatches.
- Lymphocyte aggregations (CD3+, CD4+, CD8+, CD20+) were found in 67% of failed OCA tissues, associated with insufficient osteointegration.
Conclusions:
- Donor-recipient blood type mismatches do not appear to be a significant factor in OCA transplantation failure.
- T- and B-cell-mediated subrejection immune responses may contribute to OCA treatment failure.
- Inadequate osteointegration in failed grafts is linked to lymphocytic infiltration, suggesting immune-mediated mechanisms.
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