Life Sciences & Biotechnology
Title : | Comparative profiling of the immunogenic and immunomodulatory properties between bone marrow-derived mesenchymal stem cells, migratory chondroprogenitors, fibronectin assay-derived chondroprogenitors, and chondrocytes, from non-diseased and osteoarthritic human articular cartilage |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Stem Cell Therapy, Immunology |
Principal Investigator : | Dr. Elizabeth Vinod, Christian Medical College, Vellore, Tamil Nadu |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | elsyclarence@cmcvellore.ac.in |
Details
Executive Summary : | In the field of cartilage regeneration, cell-based therapy employing chondrocytes and Mesenchymal Stem Cells have gained wide recognition. Despite the positive outcomes, the major drawback limiting its long-term effectiveness is the formation of a fibro-hyaline type of repair tissue, which is inferior in terms of its function. Search for alternative cells with enhanced chondrogenesis and a lower propensity for hypertrophy led to the discovery of articular cartilage derived chondroprogenitors. Chondroprogenitors can be isolated either by selective fibronectin adhesion assay or based on its migratory potential from cartilage explants in cultures. The current knowledge relating to the immunogenic profile and immunomodulatory potential of chondroprogenitors is notably limited. Aim: Comparative profiling of the immunogenic and immunomodulatory properties between bone marrow-derived mesenchymal stem cells, migratory chondroprogenitors, fibronectin assay-derived chondroprogenitors, and chondrocytes from non-diseased and osteoarthritic human articular cartilage. Objectives: 1. Isolate and culture bone marrow-derived mesenchymal stem cells, migratory and fibronectin adhesion assay-derived chondroprogenitors, and chondrocytes from three non-diseased and osteoarthritic articular cartilage of human knee/ankle joints. 2. Phenotypically characterize the isolated cells using flow cytometry analyses, cell cycle analysis, qRT-PCR (markers of chondrogenesis and hypertrophy) and multilineage differentiation. 3. Immunogenic profiling for a) MHC and its co-stimulatory expression b) HLA high-resolution typing c) Complement Dependent Cytotoxicity (CDC) assay d) RNA Next Gene Sequencing for immunogenic and immunomodulatory panel markers 4. Study of the immunomodulatory properties of the four cell types in a pro-inflammatory environment by a) T cell response using invitro stimulation assays b) ELISA for assessment of secreted positive and negative immunomodulators. Methods: The chondroprogenitors will be either isolated from articular cartilage by using selective fibronectin adhesion assay or based on their migratory potential from cartilage explants in cultures. Additionally, it will be compared to bone marrow MSCs and chondrocytes to assess its superiority as an allogeneic transplant material by immunoprofiling and immunomodulatory studies. Expected outcome: The comparative knowledge of chondroprogenitors from normal and osteoarthritic cartilage will help us identify the ideal source for functional chondroprogenitors. If chondroprogenitors are proven to be non-immunogenic/hypo-immunogenic with favourable immunomodulatory properties, they will be an attractive cell type for allogenic use in conditions like osteoarthritis and chondral defects. The comparative results obtained will provide knowledge on the research application of chondroprogenitors and their potential use in an allogeneic setting for regenerating damaged articular cartilage. |
Co-PI: | Dr. Alfred Job Daniel, Christian Medical College, VelloreTamil Nadu-632004, Dr. Soosai Manickam Amirtham, Christian Medical College, VelloreTamil Nadu-632004, Dr. Dolly Daniel, Christian Medical College, VelloreTamil Nadu-632004, Dr. Livingston Abel, Christian Medical College, VelloreTamil Nadu-632004, Dr. Solomon Sathishkumar, Christian Medical College, VelloreTamil Nadu-632004 |
Total Budget (INR): | 35,77,320 |
Organizations involved