Development of a Novel Large Animal Model to Evaluate Human Dental Pulp Stem Cells for Articular Cartilage Treatment

• Published in: Stem cell reviews Vol. 14; no. 5; pp. 734 - 743
• Main Authors: Fernandes, Tiago Lazzaretti, Shimomura, Kazunori, Asperti, Andre, Pinheiro, Carla Cristina Gomes, Caetano, Heloísa Vasconcellos Amaral, Oliveira, Claudia Regina G. C. M., Nakamura, Norimasa, Hernandez, Arnaldo José, Bueno, Daniela Franco
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-10-2018
• Subjects: Animals; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Cartilage Diseases - physiopathology; Cartilage Diseases - therapy; Cartilage, Articular - cytology; Cartilage, Articular - growth & development; Cell Biology; Cell Differentiation - genetics; Chondrocytes - cytology; Chondrogenesis - genetics; Dental Pulp - cytology; Humans; Life Sciences; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells - cytology; Regenerative Medicine/Tissue Engineering; Stem Cells; Stem Cells - cytology; Swine; Swine, Miniature; Tissue Engineering; Tooth, Deciduous - cytology; Human dental pulp stem cells; Hyaline cartilage, pre-clinical study, large animal model, miniature pig; Articular cartilage; Tissue engineering; Mesenchymal stem cells
• ISSN: 1550-8943; 1558-6804; 2629-3277
• DOI: 10.1007/s12015-018-9820-2

Purpose
Chondral lesion is a pathology with high prevalence, reaching as much as 63% of general population and 36% among athletes. The ability of human Dental Pulp Stem Cells (DPSCs) to differentiate into chondroblasts
in vitro
suggests that this stem cell type may be useful for tissue bioengineering. However, we have yet to identify a study of large animal models in which DPSCs were used to repair articular cartilage. Therefore, this study aimed to describe a novel treatment for cartilage lesion with DPSCs on a large animal model.
Methods
Mesenchymal stem cells (MSC) were obtained from deciduous teeth and characterized by flow cytometry. DPSCs were cultured and added to a collagen type I/III biomaterial composite scaffold. Brazilian miniature pig (BR-1) was used. A 6-mm diameter, full-thickness chondral defect was created in each posterior medial condyle. The defects were covered with scaffold alone or scaffold + DPSCs on the contralateral side. Animals were euthanized 6 weeks post-surgery. Cartilage defects were analyzed macroscopically and histology according to modified O’Driscoll scoring system.
Results
Flow cytometry confirmed characterization of DPSCs as MSCs. Macroscopic and histological findings suggested that this time period was reasonable for evaluating cartilage repair. To our knowledge, this study provides the first description of an animal model using DPSCs to study the differentiation of hyaline articular cartilage
in vivo
.
Conclusion
The animals tolerated the procedure well and did not show clinical or histological rejection of the DPSCs, reinforcing the feasibility of this descriptive miniature pig model for pre-clinical studies.