1. Evaluation of the biocompatibility and stability of allogeneic tissue-engineered cartilage in humanized mice
- Author
-
Perrier-Groult, Emeline, Pérès, Eléonore, Pasdeloup, Marielle, Gazzolo, Louis, Duc Dodon, Madeleine, Mallein-Gerin, Frédéric, Papaccio, Gianpaolo, Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département des Facteurs Humains, Service de Santé des Armées-Ministère de la Défense, Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie et chimie des protéines [Lyon] (IBCP), Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, MALLEIN-GERIN, Frédéric, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by CNRS-Lyon 1 University and Fondation ARTHRITIS (Grant obtained by Arthritis Fondation Courtin AO 2013 #105335 for EP-G)., École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Bodescot, Myriam
- Subjects
0301 basic medicine ,Cartilage, Articular ,Male ,Medical Implants ,[SDV]Life Sciences [q-bio] ,02 engineering and technology ,Osteoarthritis ,Mice, SCID ,Biochemistry ,Mice ,White Blood Cells ,Spectrum Analysis Techniques ,Mice, Inbred NOD ,Animal Cells ,Medicine and Health Sciences ,Autologous chondrocyte implantation ,Materials ,ComputingMilieux_MISCELLANEOUS ,Cells, Cultured ,Connective Tissue Cells ,[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Multidisciplinary ,Tissue Scaffolds ,Chemistry ,T Cells ,Hematopoietic Stem Cell Transplantation ,021001 nanoscience & nanotechnology ,Flow Cytometry ,3. Good health ,Cell biology ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Connective Tissue ,Spectrophotometry ,Self-healing hydrogels ,Physical Sciences ,Medicine ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Engineering and Technology ,Female ,Cytophotometry ,Anatomy ,Cellular Types ,0210 nano-technology ,Chondrogenesis ,Research Article ,Biotechnology ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Science ,Amorphous Solids ,Immune Cells ,Materials Science ,Biomaterial Implants ,Immunology ,Bioengineering ,Research and Analysis Methods ,03 medical and health sciences ,Chondrocytes ,medicine ,Animals ,Humans ,Transplantation, Homologous ,Blood Cells ,Tissue Engineering ,Cartilage ,Regeneration (biology) ,Macrophages ,Biology and Life Sciences ,Proteins ,Cell Biology ,medicine.disease ,Hematopoietic Stem Cells ,Transplantation ,[SDV.IB.BIO] Life Sciences [q-bio]/Bioengineering/Biomaterials ,030104 developmental biology ,Biological Tissue ,Mixtures ,Humanized mouse ,Medical Devices and Equipment ,Collagens ,Gels - Abstract
International audience; Articular cartilage (AC) has poor capacities of regeneration and lesions often lead to osteoarthritis. Current AC reconstruction implies autologous chondrocyte implantation which requires tissue sampling and grafting. An alternative approach would be to use scaffolds containing off-the-shelf allogeneic human articular chondrocytes (HACs). To investigate tolerance of allogeneic HACs by the human immune system, we developed a humanized mouse model implanted with allogeneic cartilage constructs generated in vitro. A prerequisite of the study was to identify a scaffold that would not provoke inflammatory reaction in host. Therefore, we first compared the response of hu-mice to two biomaterials used in regenerative medicine, collagen sponge and agarose hydrogel. Four weeks after implantation in hu-mice, acellular collagen sponges, but not acellular agarose hydrogels, showed positive staining for CD3 (T lymphocytes) and CD68 (macrophages), suggesting that collagen scaffold elicits weak inflammatory reaction. These data led us to deepen our evaluation of the biocompatibility of allogeneic tissue-engineered cartilage by using agarose as scaffold. Agarose hydrogels were combined with allogeneic HACs to reconstruct cartilage in vitro. Particular attention was paid to HLA-A2 compatibility between HACs to be grafted and immune human cells of hu-mice: HLA-A2+ or HLA-A2- HACs agarose hydrogels were cultured in the presence of a chondrogenic cocktail and implanted in HLA-A2+ hu-mice. After four weeks implantation and regardless of the HLA-A2 phenotype, chondrocytes were well-differentiated and produced cartilage matrix in agarose. In addition, no sign of T-cell or macrophage infiltration was seen in the cartilaginous constructs and no significant increase in subpopulations of T lymphocytes and monocytes was detected in peripheral blood and spleen. We show for the first time that humanized mouse represents a useful model to investigate human immune responsiveness to tissue-engineered cartilage and our data together indicate that allogeneic cartilage constructs can be suitable for cartilage engineering.
- Published
- 2019