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Presenter: Thomas, Schubert, Brussels, Belgium
Authors: Thomas Schubert1, Daela Xhema1,2, Sophie Veriter1, Michaël Schubert1, Catherine Behets3, Christian Delloye4, Pierre Gianello1, Denis Dufrane1,2
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Improvement of bone allograft by mesenchymal stem cells: undifferentiated vs. osteogenic adipose / bone marrow stem cells
Thomas Schubert1, Daela Xhema1,2, Sophie Veriter1, Michaël Schubert1, Catherine Behets3, Christian Delloye4, Pierre Gianello1, Denis Dufrane1,2
1Laboratory of Experimental Surgery; 2Endocrine Cell Therapy Unit; 3Laboratory of Experimental Morphology; 4Orthopaedic Surgery Service, UCL - Université Catholique de Louvain, Brussels, Belgium
Objectives: Lack of osteo-integration in bone allografting is a major limitation leading to progressive graft failure. Mesenchymal Stem Cells (MSCs) can improve the biological performance of acellular bone allografts. Our goal was to compare adipose (AMSCs) and bone marrow (BM-MSCs) MSCs at non-differentiated vs. osteogenic differentiated stages in view to improve the osteogenicity of bone allografts.
Material and Methods: Pig AMSCs and BM-MSCs at both non-/differentiated stages were investigated in vitro and in vivo. In vitro experiments compared the proliferation, differentiation, immunogenicity (Mixed Lymphocyte Reaction) and angiogenic (Vascular Endothelial Growth Factor (VEGF) secretion under 21%/5%/0.1% [O2]) properties of stem cells. In vivo assays assessed the angiogenesis (histomorphometry for vessel development and VEGF expression) and osteogenesis (histomorphometry for osteocalcin expression and micro-CT scan) of cultured cells seeded on a acellular bone graft and implanted in the paravertebral musculature of nude rats up to Day 30 post-transplantation.
Results: In vitro experiments demonstrated a superiority of AMSCs in terms of proliferation (6.1 ± 2.3 days vs. 9.0 ± 1.9 days for BM-MSCs, respectively, p<0.001), immunomodulation (higher T-cell depression) and a higher secretion of VEGF (4839.01 ± 2840.40 pg/ml vs. 396.30 ± 206.30 pg/ml for non-differentiated AMSCs vs. non-differentiated BM-MSCs, respectively, p<0.001).
At day 30 post-transplantation, a significantly higher angiogenesis (19.6 ± 6.8 vs. 10.9 ± 4.9 vessels/0.016mm² for differentiated AMSCs and BMSCs, respectively, p<0.005), VEGF expression (p<0.001) and osteogenesis (osteocalcin expression, p<0.001, and amount of newly formed bone matrix on micro-CT scan, p<0.05) were found for osteogenic differentiated AMSCs. It was also demonstrated that both BM-/AMSCs keep their immunomodulatory properties after osteogenic differentiation.
Conclusions: Osteogenic AMSCs are an excellent option for bone allograft revitalization in view to promote (i) cellular engraftment by local immunomodulation / neo angiogenesis and (ii) induction of osteogenesis.
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