P016 - Development and characterization of a humanized mouse model of osteoarthritis
Abstract
Purpose
Osteoarthritis (OA) is mainly characterized by cartilage breakdown and synovial inflammation. While OA is one of the most common rheumatic disorders, no efficient disease-modifying drugs still exist today. Mesenchymal stem cells (MSC) have generated significant medical considerations since they exhibit tissue-regenerative properties through the secretion of bioactive factors. Considering the pivotal role of inflammation and immune system in OA and with regards to the differences between MSC-mediated immunomodulation in human and mice (12), the development of animal models that could more closely mimic the human immune system, could be instrumental in the preclinical evaluation of MSC. Immunologically humanized mice may represent a preclinical bridge between in vitro studies and the in vivo evaluation of human stem cells in OA. Our objective is therefore to develop an experimental model of osteoarthritis by destabilizing the medial meniscus (DMM) in humanized mice.
Methods and Materials
Irradiated (1,5Gy) 4 weeks-old NOD/LtSz-scid IL2RĪ³null (NSG) mice were humanized by intravenous injection of 5.104 CD34+ human hematopoietic stem cells. 120 days after the humanization procedure, OA were surgically induced destabilization of the medial meniscus (DMM). 6 and 12 weeks after surgery the development of OA was assessed by histomorphometric analysis and histology.
Results
Our histological results show that the DMM procedure induce a significant increase in OA score at 12 weeks compared to sham mice. Our histomorphometric results also evidence a significant increase in bone volume of the anterior medial meniscus. Immunohistochemical analyses have revealed the presence of human B lymphocytes and macrophages in the subchondral bone marrow but not in the synovial membrane at 6 and 12 weeks post-surgery.
Conclusion
Our results therefore evidence the feasibility to induce OA by DMM in humanized mice. This model could constitute a useful tool to study the therapeutic efficacy of encapsulated human mesenchymal stem cells.
