TY - JOUR
T1 - BMP12 and BMP13 gene transfer induce ligamentogenic differentiation in mesenchymal progenitor and anterior cruciate ligament cells
AU - Haddad-Weber, Meike
AU - Prager, Patrick
AU - Kunz, Manuela
AU - Seefried, Lothar
AU - Jakob, Franz
AU - Murray, Martha M.
AU - Evans, Christopher H.
AU - Nöth, Ulrich
AU - Steinert, Andre F.
N1 - Funding Information:
We thank Mrs C. Amrehn, V. Monz and M. Regensburger for their excellent technical assistance. We are also grateful to Wyeth Inc. for providing the adenoviral vectors for BMP12 and BMP13 and the kind advice from Drs D. Pittman and J. Archamboult. Support to this research was given by grants from DFG (grant no. STE1051/1-1 to AFS ), BMBF (grant no. 0313386E to UN ), BayFor (FORZEBRA; TP2/WP5 to AFS and UN) and NIH (RO1, grant no. AR 052809 to CHE and AR052772 to MMM ).
PY - 2010/7
Y1 - 2010/7
N2 - Background aims. To date there are only very few data available on the ligamentogenic differentiation capacity of mesenchymal stromal/progenitor cells (MSC) and anterior cruciate ligament (ACL) fibroblasts. Methods. We describe the in vitro potential of MSC and ACL cells to undergo ligamentogenic differentiation upon transduction with adenoviral vectors encoding the human cDNA for bone morphogenetic protein (BMP) 12 and BMP13, also known as growth and differentiation factors (GDF) 6 and 7, respectively. Results. Transgene expression for at least 14 days was confirmed by Western blot analyzes. After 21 days of cell culture within collagen type I hydrogels, histochemical (hematoxylin/eosin (H&E), Azan and van Gieson), immunohistochemical and polymerase chain reaction (PCR) analyzes of the genetically modified constructs of both cell types revealed elongated, viable fibroblast-like cells embedded in a ligament-like matrix rich in collagens, vimentin, fibronectin, decorin, elastin, scleraxis, tenascin, and tenomodulin. Conclusions. It appears that both MSC and ACL fibroblasts are capable of ligamentogenic differentiation with these factors. This information may aid in the development of biologic approaches to repair and restore ACL after injury.
AB - Background aims. To date there are only very few data available on the ligamentogenic differentiation capacity of mesenchymal stromal/progenitor cells (MSC) and anterior cruciate ligament (ACL) fibroblasts. Methods. We describe the in vitro potential of MSC and ACL cells to undergo ligamentogenic differentiation upon transduction with adenoviral vectors encoding the human cDNA for bone morphogenetic protein (BMP) 12 and BMP13, also known as growth and differentiation factors (GDF) 6 and 7, respectively. Results. Transgene expression for at least 14 days was confirmed by Western blot analyzes. After 21 days of cell culture within collagen type I hydrogels, histochemical (hematoxylin/eosin (H&E), Azan and van Gieson), immunohistochemical and polymerase chain reaction (PCR) analyzes of the genetically modified constructs of both cell types revealed elongated, viable fibroblast-like cells embedded in a ligament-like matrix rich in collagens, vimentin, fibronectin, decorin, elastin, scleraxis, tenascin, and tenomodulin. Conclusions. It appears that both MSC and ACL fibroblasts are capable of ligamentogenic differentiation with these factors. This information may aid in the development of biologic approaches to repair and restore ACL after injury.
KW - Adenovirus
KW - Anterior cruciate ligament
KW - BMP12
KW - BMP13
KW - Collagen hydrogel
KW - Fibroblasts
KW - Gene transfer
KW - Mesenchymal stromal cells
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U2 - 10.3109/14653241003709652
DO - 10.3109/14653241003709652
M3 - Article
C2 - 20334610
AN - SCOPUS:77954449625
SN - 1465-3249
VL - 12
SP - 505
EP - 513
JO - Cytotherapy
JF - Cytotherapy
IS - 4
ER -