Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes
| Autor: | Esmeralda Carrillo, Gema Jiménez, Witek Kwiatkowski, Elvira Montañez, J. C. Izpisua Belmonte, Macarena Perán, Peter C. Gray, Juan A. Marchal, Senyon Choe, Francisco Arrebola, Elena López-Ruiz |
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| Přispěvatelé: | [Jiménez,G, Carrillo,E, Marchal,JA] Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada, Spain. Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain. Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada-Univesity of Granada, Granada, Spain. [López-Ruiz,E, Perán,M] Department of Health Sciences, University of Jaén, Jaén, Spain. [Kwiatkowski,W, Choe,S] Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA. [Montañez,E] Department of Orthopedic Surgery and Traumatology, Virgen de la Victoria University Hospital, Málaga, Spain. [Arrebola,F] Department of Histology, Faculty of Medicine, University of Granada, Granada, Spain. [Gray,PC] Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla CA, California, USA. [Izpisua Belmonte, JC] Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla CA, California, USA. [Choe,S] Qualcomm Institute, Univ. California, San Diego, La Jolla, USA., This work was supported by the Consejería de Economía, Innovación y Ciencia (Junta de Andalucía, excellence project number CTS-6568). |
| Rok vydání: | 2015 |
| Předmět: |
Cartilage
Articular Male Time Factors Cellular differentiation Cell Diseases::Musculoskeletal Diseases::Rheumatic Diseases::Osteoarthritis [Medical Subject Headings] Chemicals and Drugs::Hormones Hormone Substitutes and Hormone Antagonists::Hormones::Gonadal Hormones::Activins [Medical Subject Headings] Bone Morphogenetic Protein 2 Gene Expression Anatomy::Cells::Connective Tissue Cells::Chondrocytes [Medical Subject Headings] Anatomy::Tissues::Connective Tissue::Subcutaneous Tissue [Medical Subject Headings] Mice SCID Ligands Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] Extracellular matrix Mice Mice Inbred NOD Organisms::Eukaryota::Animals [Medical Subject Headings] Activinas Autologous chondrocyte implantation Tejido subcutáneo Anatomy::Cells::Cellular Structures::Extracellular Space::Extracellular Matrix [Medical Subject Headings] Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Cell Differentiation Middle Aged Immunohistochemistry Humanos Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Reverse Transcriptase Polymerase Chain Reaction [Medical Subject Headings] Activins Extracellular Matrix Cell biology Chemicals and Drugs::Carbohydrates::Polysaccharides::Proteoglycans [Medical Subject Headings] medicine.anatomical_structure Anatomy::Musculoskeletal System::Cartilage::Hyaline Cartilage::Cartilage Articular [Medical Subject Headings] Female Proteoglycans Matriz extracelular Collagen Cartílago articular Proteoglicanos Transplantation Heterologous Biology Transplantation Autologous Bone morphogenetic protein 2 Article Chondrocytes In vivo Osteoarthritis Analytical Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cytodiagnosis::Biopsy [Medical Subject Headings] medicine Animals Humans Aged Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] Reacción en cadena de la polimerasa de transcriptasa inversa Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Collagen [Medical Subject Headings] Chondrogenesis Transplantation Biopsia Condrocitos Osteoartritis Animales Immunology Colágeno |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep16400 |
| Popis: | Autologous chondrocyte implantation (ACI) depends on the quality and quantity of implanted cells and is hindered by the fact that chondrocytes cultured for long periods of time undergo dedifferentiation. Here we have developed a reproducible and efficient chondrogenic protocol to redifferentiate chondrocytes isolated from osteoarthritis (OA) patients. We used morphological, histological and immunological analysis together with a RT-PCR detection of collagen I and collagen II gene expression to show that chondrocytes isolated from articular cartilage biopsies of patients and subjected to long-term culture undergo dedifferentiation and that these cells can be redifferentiated following treatment with the chimeric Activin A/BMP2 ligand AB235. Examination of AB235-treated cell pellets in both in vitro and in vivo experiments revealed that redifferentiated chondrocytes synthesized a cartilage-specific extracellular matrix (ECM), primarily consisting of vertically-orientated collagen fibres and cartilage-specific proteoglycans. AB235-treated cell pellets also integrated into the surrounding subcutaneous tissue following transplantation in mice as demonstrated by their dramatic increase in size while non-treated control pellets disintegrated upon transplantation. Thus, our findings describe an effective protocol for the promotion of redifferentiation of autologous chondrocytes obtained from OA patients and the formation of a cartilage-like ECM that can integrate into the surrounding tissue in vivo. |
| Databáze: | OpenAIRE |
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