Chondrogenic differentiation of human mesenchymal stem cells in micro-masses is impaired by high doses of the chemokine CXCL7.
Chemokines have been shown to recruit human mesenchymal stem cells (MSCs) and are suggested to be promising candidates for in situ tissue engineering. The aim of our study was to analyse the effect of CXCL7, a chemokine that has the capacity to recruit MSCs, on the chondrogenic differentiation of MSCs. Bone marrow-derived MSCs were cultured in high-density micro-masses under serum-free conditions and were co-stimulated with 0-100 nM CXCL7 in the presence of 10 ng/ml transforming growth factor-β3 (TGFβ3). Micro-masses stimulated without growth factors and chemokines served as controls. Histological staining of proteoglycan, immunostaining of type II collagen, staining of mineralized matrix according to von Kossa as well as real-time gene expression analysis of typical chondrogenic and osteogenic marker genes showed that the TGFβ3-mediated chondrogenic development of MSCs was not impaired by 0-50 nM CXCL7. Micro-masses stimulated with TGFβ3 and CXCL7 developed chondrogenic cells and formed a cartilaginous matrix rich in proteoglycans, accompanied by the induction of typical chondrogenic marker genes, such as cartilage oligomeric matrix protein, aggrecan, type IIα1 collagen and by regulation of matrix metalloproteinases and their inhibitors. As assessed by histological staining, MSCs showed a significantly reduced deposition of proteoglycan and a mildly mineralized matrix when stimulated with TGFβ3 in the presence of 100 nM CXCL7. Induction of osteogenic marker genes such as osteocalcin was not evident. These results suggest that low doses of CXCL7 do not impair the chondrogenic differentiation of bone marrow-derived stem cells and may suited for in situ cartilage tissue engineering.
Kalwitz
Gregor
G
TransTissue Technologies GmbH, Tucholskystrasse 2, 10117 Berlin, Germany.
Neumann
Katja
K
Ringe
Jochen
J
Sezer
Orhan
O
Sittinger
Michael
M
Endres
Michaela
M
Kaps
Christian
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D019743:Chemokines, CXC / Q000494:pharmacology*; D020219:Chondrogenesis / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology
D000954:Antigens, Surface; D019743:Chemokines, CXC; D053782:Transforming Growth Factor beta3