Cartilage Regeneration - a biomimicry approach recapitulating fetal-like regeneration
Abstract
The proposed project is designed to test the hypotheses that successful cartilage regeneration requires the recapitulation of embryogenic processes and that the secretome of fetal cells can initiate fetal-like regeneration of cartilage. Osteoarthritis (OA), a degenerative joint disease characterized by progressive articular cartilage degeneration, is one of the leading causes of disability worldwide and is associated with a tremendous individual and socioeconomic burden. Adult articular cartilage (AAC) has limited intrinsic repair capacity and current medical treatment options provide only symptomatic relief without significantly altering the disease progression or restoring cartilage integrity. Therefore, injured cartilage does not regenerate but forms fibrocartilaginous repair tissue with impaired biomechanical properties which does not adequately substitute for hyaline cartilage, thereby precipitating the continuation of joint inflammation leading to chronic osteoarthritis. In contrast to AAC, fetal articular cartilage (FAC) subjected to partial thickness lesions fully regenerates. In addition, fetal cells transplanted into an adult organism have been shown to retain their regenerative potential in skin, liver, tendon and cartilage models. Information on regenerative healing in fetal animals may allow improvement of the healing response in mature tissue. The cell secretome has a key role in tissue regeneration but is poorly understood. An improved knowledge of the factors involved in healing is a key prerequisite for utilizing this potentially powerful tool for therapeutic applications. We intend to develop a novel, biomimetic treatment strategy, recapitulating aspects of fetal articular cartilage morphogenesis to achieve fetal-like regeneration of adult articular cartilage. We propose to carry out a comprehensive study comparing 1) fetal (gestational day 80, term ~ 145 days of gestation) and adult cartilage healing in vivo 2) the effect of fetal chondrocytes, fetal mesenchymal stem cells (fMSCs), adult chondrocytes and adult bone marrow derived mesenchymal stem cells (aMSCs) and the secretome of these 4 cell types on adult articular chondrocyte proliferation, chondrogenic matrix production, and gene expression in vitro and 3) to identify key factors responsible for the induction of fetal healing rather than adult repair. The achieved knowledge will lead to further developmental work following up the proposed project, in order to establish an economically exploitable therapy approach, which will induce fetal healing in adult cartilage. The novel therapy will give the company partner involved in this project a competitive edge in this field at an international level.
Publikationen
Project staff
David Philip Kreil
Assoc. Prof. Dr. David Philip Kreil
d.kreil@boku.ac.at
Tel: +43 1 47654-79171
BOKU Project Leader
01.03.2017 - 28.02.2021
Sinan Gültekin
Dr.phil. Sinan Gültekin
sinan.gueltekin@boku.ac.at
Tel: +43 1 47654-79172
Project Staff
01.03.2017 - 28.02.2021