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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
Functionally deficient mesenchymal stem cells reside in the bone marrow niche with M2-macrophages and amyloid-β
Bryan S Margulies1, Sean D DeBoyace, Adrienne M Parsons
1Department of Orthopedic Surgery, SUNY Upstate Medical University, Syracuse, New York.
Abstract:
We sought to demonstrate whether there is a difference in the local mesenchymal stem cells (MSC) niche obtained from patients undergoing their first total joint replacement surgery versus those patients undergoing a revision surgery for an failing total joint implant. Bone marrow aspirates collected from patients undergoing revision total joint arthroplasty were observed to be less clonal and the expression of PDGFRα, CD51, ALCAM, endoglin, CXCL12, nestin, and nucleostemin were decreased. Revision MSC were also less able to commit to an osteoblast-lineage or an adipocyte-lineage. Further, in revision MSC, OPG, and IL6 expression were increased. Monocytes, derived from revision whole marrow aspirates, were less capable of differentiating into osteoclasts, the cells implicated in the pathologic degradation of bone. Osteoclasts were also not observed in tissue samples collected adjacent to the implants of revision patients; however, the alternatatively activated M2-macrophage phenotype was observed in parallel with pathologic accumulations of amyloid-β, τ-protien and 3-nitrotyrosine. Despite the limited numbers of patients examined, our data suggest that nucleostemin may be a useful functional marker for MSC while the observation of M2-macrophage infiltration around the implant lays the foundation for future investigation into a novel mechanism that we propose is associated with loose total joint implants.
Insights
Mesenchymal stem cells (MSC) from revision joint replacement patients show reduced differentiation potential and altered gene expression compared to first-time surgery patients. This suggests a novel mechanism contributing to implant loosening.
Area of Science:
- Orthopedics
- Regenerative Medicine
- Cell Biology
Background:
- Total joint replacement (TJR) is a common procedure, but implant revision due to failure is a growing concern.
- The local bone marrow microenvironment, including mesenchymal stem cells (MSCs), plays a critical role in bone healing and implant integration.
- Understanding differences in MSCs between primary and revision surgeries may reveal mechanisms of implant failure.
Purpose of the Study:
- To investigate the differences in the mesenchymal stem cell (MSC) niche between patients undergoing first-time total joint replacement (TJR) and those requiring revision surgery.
- To characterize the functional and molecular properties of MSCs and monocytes in the context of failed joint implants.
Main Methods:
- Bone marrow aspirates were collected from patients undergoing primary TJR and revision TJR.
- Flow cytometry and gene expression analysis were used to assess MSC characteristics, including clonality and expression of specific markers (PDGFRα, CD51, ALCAM, endoglin, CXCL12, nestin, nucleostemin).
- Osteoclast differentiation potential of monocytes and the presence of M2-macrophages and pathological markers (amyloid-β, τ-protein, 3-nitrotyrosine) were examined in tissue samples.
Main Results:
- Revision MSCs exhibited decreased clonality and reduced expression of key markers compared to primary MSCs.
- Revision MSCs showed impaired osteogenic and adipogenic differentiation potential, with increased OPG and IL6 expression.
- Monocytes from revision patients had reduced osteoclast differentiation capacity, and M2-macrophages were observed near implants in revision cases, correlating with pathological protein accumulation.
Conclusions:
- The MSC niche is altered in patients requiring revision TJR, characterized by reduced stemness and differentiation capacity.
- Nucleostemin may serve as a functional marker for MSCs in this context.
- The presence of M2-macrophages and associated pathological proteins suggests a novel inflammatory mechanism contributing to aseptic loosening of total joint implants.
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