Repair of chronic osteochondral defects using predifferentiated mesenchymal stem cells in an ovine model.
BACKGROUND
The use of mesenchymal stem cells (MSCs) to treat osteochondral defects caused by sports injuries or disease is of particular interest. However, there is a lack of studies in large-animal models examining the benefits of chondrogenic predifferentiation in vitro for repair of chronic osteochondral defects.


OBJECTIVE
Chondrogenic in vitro predifferentiation of autologous MSCs embedded in a collagen I hydrogel currently in clinical trial use for matrix-associated autologous chondrocyte transplantation facilitates the regeneration of a chronic osteochondral defect in an ovine stifle joint.


METHODS
Controlled laboratory study.


METHODS
The optimal predifferentiation period of ovine MSCs within the type I collagen hydrogel in vitro was defined by assessment of several cellular and molecular biological parameters. For the animal study, osteochondral lesions (diameter 7 mm) were created at the medial femoral condyles of the hind legs in 10 merino sheep. To achieve a chronic defect model, implantation of the ovine MSCs/hydrogel constructs was not performed until 6 weeks after defect creation. The 40 defects were divided into 4 treatment groups: (1) chondrogenically predifferentiated ovine MSC/hydrogel constructs (preMSC-gels), (2) undifferentiated ovine MSC/hydrogel constructs (unMSC-gels), (3) cell-free collagen hydrogels (CF-gels), and (4) untreated controls (UCs). Evaluation followed after 6 months.


RESULTS
With regard to proteoglycan content, cell count, gel contraction, apoptosis, compressive properties, and progress of chondrogenic differentiation, a differentiation period of 14 days in vitro was considered optimal. After 6 months in vivo, the defects treated with preMSC-gels showed significantly better histologic scores with morphologic characteristics of hyaline cartilage such as columnarization and presence of collagen type II.


CONCLUSIONS
Matrix-associated autologous chondrocyte transplantation with predifferentiated MSCs may be a promising approach for repair of focal, chronic osteochondral defects.


CONCLUSIONS
The results suggest an encouraging method for future treatment of focal osteochondral defects to prevent progression to osteoarthritis.
Zscharnack
Matthias
M
Department of Cell Techniques and Applied Stem Cell Biology, Center of Biotechnology and Biomedicine, University of Leipzig, Deutscher Platz 5, D-04103 Leipzig, Germany. Matthias.Zscharnack@bbz.uni-leipzig.de
Hepp
Pierre
P
Richter
Robert
R
Aigner
Thomas
T
Schulz
Ronny
R
Somerson
Jeremy
J
Josten
Christoph
C
Bader
Augustinus
A
Marquass
Bastian
B
D000818:Animals; D002358:Cartilage, Articular / Q000502:physiology* / Q000601:surgery*; D002454:Cell Differentiation / Q000235:genetics; D020219:Chondrogenesis; D024043:Collagen Type II / Q000378:metabolism; D015870:Gene Expression; D048091:Guided Tissue Regeneration / Q000379:methods*; D006614:Hindlimb; D020100:Hydrogels; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D023421:Models, Animal; D012038:Regeneration; D012756:Sheep; D018709:Statistics, Nonparametric; D013264:Stifle / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds; D014182:Transplantation, Autologous
D024043:Collagen Type II; D020100:Hydrogels