Regulatory Science Symposium: “Innovations in Regenerative Medicine Products” - Session 3: Translational Approach and Use of Stem Cells for Arthritis and Articular Cartilage Restoration

Syllabus/Topics

1. Topics covered
2. Review of problems associated with arthritis
3. Technologies preclinical studies conducted
4. Feedback from FDA
5. What are synovial joints?
6. A structure where bones connect to move body parts.
7. ~200 bones and ~250 joins in body
8. Articular cartilage is thin and is composed of unique tissue.
9. Diseases of synovial joint:
   1. Osteoarthritis is the most highly observed disease
   2. Focal cartilage lesions
10. Treatments:
    1. Microfracture surgery
    2. Autologous chondrocyte implants
    3. Other Procedures:
    4. AMIC procedure
    5. Infusion of mesenchymal cells
    6. Diseases are identified based on their symptoms
    7. None of the cell types can grow proper cartilage in humans
    8. Some not FDA-Approved
    9. Specification of articular cartilage cells in humans (Development)
11. Morula (pluripotent stem cells): Day 1
12. Gastrulation: 21 day
13. Multipotent skeleton progenitors: 4 to 6 weeks
14. Functional chondrocytes: 7 to 8 weeks
15. Stable articular cartilage: after 8 weeks
16. Embryonic cells and induced pluripotent stem cells
    1. Sources of pluripotent stem cells
    2. Developmental chondrogenesis
       1. This study was done on mice to understand the process and maintenance
17. Protocol to prepare juvenile cartilage cells
18. Conceptual studies
19. Pluocart Development Team
20. Manufacturing and Controls (GMP)
    1. Production and release of Master and Working Cell banks of initial cell type will make a product that will be produced under GMP conditions
    2. Technology transfer & manufacturing of the Pluocart implants for Phase 1 Clinical Trial under GMP standards
    3. FDA requested GLP Safety Studies
       1. Assessment of tumorigenicity and adverse events in vivo
       2. Phase 1 study: The primary objective was the safety evaluation of Plutocrat as measured via adverse event monitoring
21. 2022 Clinical award from CRIM
22. Summary
    1. Systematic analysis of human developmental chondrogenesis defined critical parameters for large-scale manufacturing of functional juvenile articular chondrocytes from Human PSC
    2. Pluocart is a new-generation bioimplant
    3. “First-in-man” Phase 1 trial of Pluocart for small and large cartilage lesions scheduled in years to come
23. Questions
    
    

Acknowledgment
Accompanying text created by Roxy Terteryan, RKS Project Administrator, SC CTSI (atertery@usc.edu)