PMID- 15738660 OWN - NLM STAT- MEDLINE DCOM- 20050623 LR - 20220317 IS - 1076-3279 (Print) IS - 1076-3279 (Linking) VI - 11 IP - 1-2 DP - 2005 Jan-Feb TI - Modulation of proliferation and differentiation of human bone marrow stromal cells by fibroblast growth factor 2: potential implications for tissue engineering of tendons and ligaments. PG - 41-9 AB - Bone marrow stromal cells (BMSCs) play a central role in the repair and regeneration of mesenchymal tissues. For tissue engineering of ligaments and tendons, both stimulation of cell proliferation and differentiation with increased expression of essential extracellular matrix proteins and cytoskeletal elements are desirable. This study analyzes the effect of low-dose (3 ng/mL) fibroblast growth factor 2 (FGF-2) and high-dose FGF-2 (30 ng/mL) on proliferation (bromodeoxyuridine content, spectrophotometry), differentiation (transcription of collagen I, collagen III, fibronectin, elastin, alpha-smooth muscle actin, and vimentin, reverse transcription-polymerase chain reaction, and cell density and apoptosis (annexin V, fluorescence-activated cell sorting) of human BMSCs, and compares the results with those of a control group without FGF-2. Low-dose FGF-2 triggered a biphasic BMSC response: on day 7, cell proliferation reached its maximum and was significantly higher compared with the other groups. On days 14 or 28, collagen I, collagen III, fibronectin, and alpha- smooth muscle actin mRNA expression was significantly enhanced in the presence of low-dose FGF-2. In contrast, high-dose FGF-2 did not stimulate differentiation or proliferation. Vimentin mRNA was expressed only in cultures with low-dose and high-dose FGF-2 after 14 and 28 days. Cell density was significantly higher in cultures with low-dose FGF-2 compared with the group with high-dose FGF-2 on days 7, 14, and 28. The apoptosis rate remained stable, at a rather high level, in all groups. Microscopic investigation of the cell cultures with low-dose FGF-2 showed more homogeneous, dense, fibroblast-like, spindle-shaped cells with long cell processes compared with cultures with high-dose, or no FGF-2. Low-dose FGF-2 may be useful for tissue engineering of ligaments and tendons by increasing BMSC proliferation and stimulating mRNA expression of specific extracellular matrix proteins and cytoskeletal elements. FAU - Hankemeier, Stefan AU - Hankemeier S AD - Trauma Department, Hannover Medical School (MHH), Hannover, Germany. hankemeier.stefan@mh-hannover.de FAU - Keus, Michaela AU - Keus M FAU - Zeichen, Johannes AU - Zeichen J FAU - Jagodzinski, Michael AU - Jagodzinski M FAU - Barkhausen, Tanja AU - Barkhausen T FAU - Bosch, Ulrich AU - Bosch U FAU - Krettek, Christian AU - Krettek C FAU - Van Griensven, Martijn AU - Van Griensven M LA - eng PT - Journal Article PL - United States TA - Tissue Eng JT - Tissue engineering JID - 9505538 RN - 103107-01-3 (Fibroblast Growth Factor 2) SB - IM MH - Bone Marrow Cells/*cytology/drug effects/*metabolism MH - Cell Proliferation/*drug effects MH - Dose-Response Relationship, Drug MH - Fibroblast Growth Factor 2/*pharmacology MH - Humans MH - Ligaments MH - Stromal Cells/cytology/*drug effects/metabolism MH - Tendons MH - Tissue Engineering/*methods EDAT- 2005/03/02 09:00 MHDA- 2005/06/24 09:00 CRDT- 2005/03/02 09:00 PHST- 2005/03/02 09:00 [pubmed] PHST- 2005/06/24 09:00 [medline] PHST- 2005/03/02 09:00 [entrez] AID - 10.1089/ten.2005.11.41 [doi] PST - ppublish SO - Tissue Eng. 2005 Jan-Feb;11(1-2):41-9. doi: 10.1089/ten.2005.11.41.