Heterogeneous outcomes of autologous chondrocyte implantation for full-thickness cartilage damage: Surprise from macrophage and mast cell responses

Abstract

We read with great interest the article by Pawelczyk et al. on the capabilities of combined all-arthroscopic meniscal allograft transplantation (MAT) and autologous chondrocyte implantation (ACI) for treating meniscal insufficiency and coexisting full-thickness cartilage defects [8]. We were particularly intrigued by their observation of significant improvements in patient outcomes, which contrasted with the superior outcomes typically associated with isolated MAT, as reported in recent meta-analyses. This discrepancy suggests that the outcomes of the combined surgical approach may be somewhat less favourable, a point that Pawelczyk et al. did not fully explore or explain, leaving an intriguing gap in our understanding of causality related to heterogeneous immunologic responses.

The interaction between allogeneic tissues and the immune system is a well-documented phenomenon [1]. Recent studies have shed light on how this relationship can be altered by the introduction of cultured autologous chondrocytes. These changes in the immune response are of particular interest in the context of combined MAT and ACI procedures.

Recent studies have notably found an association between ACI and macrophage recruitment, along with a decrease in implant stability [1]. This phenomenon is thought to be related to changes in M1/M2 macrophage polarisation induced by ACI. Pro-inflammatory macrophage polarisation leads to increased cartilage degeneration [4]. Mast cells and macrophages play crucial roles in cell senescence, release of SASP and following cartilage injury or repair [6]. Mast cells promote cartilage matrix degradation by inducing the production of matrix metalloproteinases and activating M1 macrophages to secrete inflammatory factors. Additionally, regulating cell-specific interactions of mast cells with materials could sufficiently improve implantation outcomes [3, 7]. Studies on chondrocytes seeded on the material have shown that complete cartilage healing did not occur ad integrum, and cartilage formation from the perichondrium was more irregular than from the seeded scaffold [2]. These changes correlate with increased mast cell infiltration at the implant site [5]. This interaction between ACI and the recipient's immune response represents a complex dynamic that may explain the slightly inferior outcomes observed by Pawelczyk et al. following combined surgery.

We believe that understanding the cause of the heterogeneity of macrophage and mast cell immunological responses is critical to advancing our understanding of the potential benefits and limitations of combining MAT and ACI procedures. Investigating the bidirectional effects underlying the immunological responses of the ACI recipient is essential to improving the treatment of meniscal insufficiency and chondral defects, ultimately improving patient care and outcomes.

Conceptualisation and design: Ilya Klabukov and Denis Baranovskii. Manuscript writing, all authors. All authors have read and agreed to the published version of the manuscript.

The authors declare no conflict of interest.

The authors have nothing to report.