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Selection of specific human articular chondrocyte populations for reproducible and enhanced engineering of cartilage grafts

Applicant Mainil-Varlet Pierre
Number 58623
Funding scheme NRP 46 Implants and Transplants
Research institution Institut für Pathologie Medizinische Fakultät Universität Bern
Institution of higher education University of Berne - BE
Main discipline Cellular Biology, Cytology
Start/End 01.02.2001 - 31.12.2005
Approved amount 844'390.00
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Lay Summary (English)

Lead
Lay summary
Engineering Human Cartilaginous Implants in Bioreactors Using Mature Chondrocytes and Mesenchymal Progenitor Cells from Donors of Different Age Groups: A Collaborative Study by Two Institutions

Intermediate Results May 2002

Background
Today, new molecular techniques can be used to monitor the differentiation of chondrogenic cells and to identify differential patterns of gene expression among cell populations. Furthermore, use of recently available human recombinant growth factors may induce a more effective generation of implants. Recently, animal experiments have shown that cartilaginous tissues generated in vitro and grafted into cartilage defects can lead to histological and functional consolidation of articular surfaces.

Problem
However, engineering equivalents of human cartilage tissue from culture-expanded autologous cells has not yet been achieved. Human chondrocytes harvested form normal articular cartilage dedifferentiate into a fibroblastic stage during in vitro expansion in monolayers, and - particularly if cells are from old donors - they fail to reproducibly redifferentiate and to generate a functional matrix after expansion. Human mesenchymal progenitor cells (MPC) harvested from the bone marrow, although able to display a chondrogenic potential after expansion, have yet to be shown to reach and maintain a stable articular chondrocyte phenotype.

Objective
The project pursues the following objectives: (i) to identify donor age related differences in the pattern of gene expression of normal human articular chondrocytes and MPC; (ii) to define markers of chondrocytes in native cartilage; (iii) to enhance the chondrogenic potential of chondrocytes and MPC; and (iv) to improve production and accumulation of cartilage-specific extracellular matrix by enpanded chondrocytes and MPC.

Approach
The hypotheses of our poposed collaborative research are (i) that differences in the patterns of gene expression of primary chondrocytes from donors of different age groups may be used to identify markers correlating with the cell's chondrogenic potential; (ii) that exogenously applied molecules and bioreactor conditions can modulate the differentiation and extracellular matrix production of culture-expanded human chondrocytes and

Direct link to Lay Summary Last update: 21.02.2013

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