Chondrogenic differentiation of human mesenchymal stem cells in micro-masses is impaired by high doses of the chemokine CXCL7.
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Chondrogenic differentiation of human mesenchymal stem cells in micro-masses is impaired by high doses of the chemokine CXCL7. / Kalwitz, Gregor; Neumann, Katja; Ringe, Jochen; Sezer, Orhan; Sittinger, Michael; Endres, Michaela; Kaps, Christian.
In: J TISSUE ENG REGEN M, Vol. 5, No. 1, 1, 2011, p. 50-59.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Chondrogenic differentiation of human mesenchymal stem cells in micro-masses is impaired by high doses of the chemokine CXCL7.
AU - Kalwitz, Gregor
AU - Neumann, Katja
AU - Ringe, Jochen
AU - Sezer, Orhan
AU - Sittinger, Michael
AU - Endres, Michaela
AU - Kaps, Christian
PY - 2011
Y1 - 2011
N2 - 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-?3 (TGF?3). 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 TGF?3-mediated chondrogenic development of MSCs was not impaired by 0-50 nM CXCL7. Micro-masses stimulated with TGF?3 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 II?1 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 TGF?3 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.
AB - 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-?3 (TGF?3). 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 TGF?3-mediated chondrogenic development of MSCs was not impaired by 0-50 nM CXCL7. Micro-masses stimulated with TGF?3 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 II?1 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 TGF?3 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.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Immunohistochemistry
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Gene Expression Regulation/drug effects
KW - Antigens, Surface/metabolism
KW - Calcification, Physiologic/drug effects
KW - Cell Aggregation/drug effects
KW - Cell Differentiation/drug effects/genetics
KW - Chemokines, CXC/pharmacology
KW - Chondrogenesis/drug effects/genetics
KW - Mesenchymal Stem Cells/cytology/drug effects/metabolism
KW - Osteogenesis/drug effects/genetics
KW - Transforming Growth Factor beta3/pharmacology
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Immunohistochemistry
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Gene Expression Regulation/drug effects
KW - Antigens, Surface/metabolism
KW - Calcification, Physiologic/drug effects
KW - Cell Aggregation/drug effects
KW - Cell Differentiation/drug effects/genetics
KW - Chemokines, CXC/pharmacology
KW - Chondrogenesis/drug effects/genetics
KW - Mesenchymal Stem Cells/cytology/drug effects/metabolism
KW - Osteogenesis/drug effects/genetics
KW - Transforming Growth Factor beta3/pharmacology
M3 - SCORING: Journal article
VL - 5
SP - 50
EP - 59
JO - J TISSUE ENG REGEN M
JF - J TISSUE ENG REGEN M
SN - 1932-6254
IS - 1
M1 - 1
ER -
