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HUMAN MESENCHYMAL STEM CELLS REGENERATE MATURE BONE AND MITIGATE INFLAMMATION IN A XENOTRANSPLANTATION MODEL
Presenter: Anisa Yalom, MD
Co-Authors: Bueno DF; Li A; Buck A; Hokugo A; Zuk P; Nguyen P; Eduardo C; Amaral R; Bueno MRP; Jarrahy R
UCLA REBAR Lab

Background: Tissue engineering relies on the ability to isolate, expand, and deliver populations of pluripotent cells that have regenerative capacity. Complex defects and recalcitrant wounds are characterized by presence of inflammatory tissue, which can hinder the regenerative potential of stem cells. The intricate relationship between inflammation and regenerative repair is poorly understood, but its understanding is crucial to the development of clinically relevant solutions in regenerative transplant medicine. The purpose of this study is to elucidate some of the characteristics of that relationship.

Methods: Stem cells derived from human orbicularis oris muscle and human dental pulp were isolated and expanded as previously described. Both cell types were used to reconstruct critical-sized calvarial vault defects (5x8 mm) in immunocompetent 320-420g Wistar rats. 1x106 cells were seeded onto collagen scaffolds and incubated for 24 hours prior to implantation into the cranial defects. Animals were euthanized after 30 days and the reconstructed areas were analyzed for the presence bone regeneration, viable human cells, and inflammatory cells via immunohistochemistry and histological analysis.

Results: Histological analysis of prepared specimens showed increased and more mature bone formation in defects reconstructed with mesenchymal stem cells compared to controls. DNA analysis of the areas of new bone formation confirmed the presence of viable human cells in the bone matrix. Inflammation was significantly decreased in the defects treated with human stem cells compared to those treated with scaffolds alone.

Conclusions: To our knowledge, this is the first documentation of human stem cells reconstructing a bone defect in an immunocompetent animal of another species. Cells were able to regenerate mature bone and mitigate the inflammatory process. The mechanisms behind this immunomodulatory effect have yet to be fully elucidated, and they are currently under investigation in our research.


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