FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells.
Human mesenchymal stem cells (hMSCs) expanded with and without fibroblast growth factor (FGF) supplementation were compared with respect to their proliferation rate, ability to differentiate along the chondrogenic pathway in vitro, and their gene expression profiles. hMSCs expanded in FGF-supplemented medium were smaller and proliferated more rapidly than hMSCs expanded in control conditions. Chondrogenic cultures made with FGF-treated cells were larger and contain more proteoglycan than those made with control cells. Furthermore, aggregates of FGF-treated cells lacked the collagen type I-positive and collagen type II-negative outer layer characteristic of aggregates of control cells. A total of 358 unique transcripts were differentially expressed in FGF-treated hMSCs. Of these, 150 were upregulated and 208 downregulated. Seventeen percent of these genes affect proliferation. Known genes associated with cellular signaling functions comprised the largest percentage ( approximately 20%) of differentially expressed transcripts. Eighty percent of differentially expressed extracellular matrix-related genes were downregulated. The present findings that FGF-2 enhances proliferation and differentiation of hMSCs adds to a growing body of evidence that cytokines modulate the differentiation potential and, perhaps, the multipotentiality of adult stem cells. With the generation of gene expression profiles of FGF-treated and control cells we have taken the first steps in the elucidation of the molecular mechanism(s) behind these phenomena.
Solchaga
Luis A
LA
Department of Orthopaedics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. luis.solchaga@case.edu
Penick
Kitsie
K
Porter
John D
JD
Goldberg
Victor M
VM
Caplan
Arnold I
AI
Welter
Jean F
JF
D000367:Age Factors; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020219:Chondrogenesis / Q000187:drug effects* / Q000502:physiology; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008938:Mitosis / Q000187:drug effects / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011509:Proteoglycans / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D016222:Fibroblast Growth Factor 2; D003094:Collagen