ICRS 2018 - Conference Calendar
Found 1 Presentation For Request "primate"
P116 - Use of autologous chondrocyte-seeded hydrogel to treat focal cartilage defect in non-human primate (ID 10068)
In vivo evaluation of tissue engineered-cartilage is an indispensable step before human application. Most animal models differ in biomechanical functions and/or physiological responses from human, limiting our ability to extrapolate data to clinical practice. The non-human primate (NHP) model overcomes many of these limitations. We have developed a new technology for articular cartilage repair: autologous chondrocytes are amplified and combined to self-assembling peptide hydrogel (IEIK13), under stimulation of chondrogenic factors. We investigated repair capacity of this cartilage construct in osteochondral defect created in the joint of a Cynomolgus monkey model.
Methods and Materials
Chondrocytes are recovered from a small biopsy of cartilage and expanded in vitro with a first cocktail of soluble factors (FI: FGF-2 + insulin) which induces chondrocyte dedifferentiation. Cells are then seeded in hydrogel and re-differentiation is induced with a second cocktail (BIT: BMP-2 + insulin + T3). Drug forms of these soluble factors along with newly patented hydrogel (IEIK13) are used in view of rapid clinical application. Three animals are used in this study and acellular gels or fibrin gels are used as controls. Implant integration is evaluated by micro-computed tomography and immunohistological analyses.
Our pilot studies indicate that cells harvested from a 2-3 mm3 cartilage biopsy can generate 4-5 ml of cartilage gel containing 2.106 cells/ml. In vitro analyses (real-time PCR, Western-blotting and immunohistochemistry) reveal that NHP chondrocytes are able to reconstruct a cartilage matrix in IEIK13 and fibrin hydrogels. Furthermore, our surgery feasibility study shows that implantation sites in non-weight bearing area are well adapted for assessing implant integration. The pre-clinical experimentation is in progress.
Our results demonstrate the value of a combined approach using autologous chondrocytes, selected factors and hydrogel to reconstruct cartilage in vitro. The NHP model offers the possibility to investigate integration of the cartilage gel and repair of the defect in vivo.