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Tissue Eng Part A. 2009 Oct 20.
FIBROBLAST GROWTH FACTOR-2 ENHANCES PROLIFERATION AND DELAYS LOSS OF CHONDROGENIC POTENTIAL IN HUMAN ADULT BONE MARROW-DERIVED MESENCHYMAL STEM CELLS.
Solchaga LA, Penick K, Goldberg VM, Caplan AI, Welter JF.
Case Western Reserve University, General Medical Sciences: Hematology and Oncology, Cleveland, Ohio, United States, 1-216-368-4077; [email protected].
We compared human mesenchymal stem cells (hMSCs), expanded long-term with and without fibroblast growth factor (FGF) supplementation, with respect to proliferation, and ability to undergo chondrogenesis in vitro. hMSCs expanded in FGF-supplemented medium proliferated more rapidly than control cells. Aggregates of FGF-treated cells exhibited chondrogenic differentiation at all passages tested although, in some preparations, differentiation was diminished after seventh passage. Aggregates made with control cells differentiated along the chondrogenic lineage after first passage but exhibited only marginal differentiation after fourth and failed to form cartilage after seventh passage. Microarray analysis of gene expression identified 334 transcripts differentially expressed in fourth passage control cells which had reduced chondrogenic potential, compared to fourth passage FGF-treated cells which retained this capacity, and 243 transcripts that were differentially expressed when comparing them to first passage control cells which were also capable of differentiating into chondrocytes. The intersection of these analyses yielded 49 transcripts differentially expressed in cells that exhibited chondrogenic differentiation in vitro compared to cells that did not. Among these, ANGPT1, SFRP1 and STEAP1 appear to be of higher relevance. These preliminary data must now be validated to verify whether different gene expression profiles translate into functional differences. In sum, these findings suggest that the chondrogenic potential of hMSCs is vulnerable to cell expansion and that care should be exercised when expanding these cells for cartilage tissue engineering applications. Supplementation with FGF-2 allows reaching target cell numbers more rapidly and extends the level of expansion within which these cells are useful for tissue-engineered cartilage repair.
Arthroscopy. 2009 Jun;25(6):608-16. Epub 2009 Jan 24.
The effects of fibroblast growth factor-2 on rotator cuff reconstruction with acellular dermal matrix grafts.
Ide J, Kikukawa K, Hirose J, Iyama K, Sakamoto H, Mizuta H.
Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. [email protected]
PURPOSE: Our purpose was to determine whether the local application of fibroblast growth factor (FGF) 2 accelerates regeneration and remodeling of rotator cuff tendon defects reconstructed with acellular dermal matrix (ADM) grafts in rats. METHODS: Thirty adult male Sprague-Dawley rats were divided into equal groups undergoing FGF-treated and FGF-untreated repairs. All rats underwent placement of an ADM graft for the supraspinatus defect (3 x 5 mm). FGF-2 (100 microg/kg) in a fibrin sealant was applied to both shoulders in the FGF-treated group, whereas only fibrin sealant was applied in untreated group. At 2, 6, and 12 weeks after surgery, 5 rats (10 shoulders) in each group were sacrificed for histologic analysis (3 shoulders) and biomechanical testing (7 shoulders). The controls were 5 unoperated rats (3 histologic and 7 biomechanical control specimens). RESULTS: Unoperated control tendons inserted into the bone by direct insertion; there was a zone of fibrocartilage between the tendon and bone. At 2 weeks, the FGF-treated group had tendon maturing scores similar to those in the untreated group (P > .05). At 6 and 12 weeks, the FGF-treated group had significantly higher scores (P < .05). At 2 weeks, specimens in both the treated and untreated groups exhibited similar strength; the ultimate tensile failure load was 6.0 +/- 4.0 N and 5.8 +/- 2.0 N, respectively (P > .05). At 6 weeks, the FGF-treated specimens were stronger, with an ultimate tensile failure load of 10.2 +/- 3.1 N compared with 7.2 +/- 2.2 N in the untreated group (P = .02). At 12 weeks, the FGF-treated specimens were stronger, with an ultimate tensile failure load of 15.9 +/- 1.6 N compared with 13.2 +/- 2.0 N in the untreated group (P = .0072), and there were no significant differences in strength compared with the controls (17.8 +/- 2.6 N) (P > .05). CONCLUSIONS: The remodeling of ADM grafts placed in rat rotator cuff tendon defects was accelerated by the local administration of FGF-2. CLINICAL RELEVANCE: The application of FGF-2 may result in improved histologic characteristics and biomechanical strength in ADM graft constructs in humans.
Tissue Eng Part A. 2009 Jul 8. [Epub ahead of print]
Modulation of proliferation and differentiation of human anterior cruciate ligament derived stem cells by different growth factors.
Cheng MT, Yang HW, Chen TH, Lee OK.
National Yang-Ming University, Institute of Clinical Medicine, Taipei, Taiwan; [email protected].
We have previously isolated and identified stem cells from human cruciate ligaments. The goal of this study is to evaluate the proliferation and differentiation abilities of ligament-derived stem cells (LSCs) cultured with growth factors including fibroblast growth factor 2 (FGF-2), epidermal growth factor (EGF), and transforming growth factor-beta 1 (TGF-b1). The ligament tissues were obtained from patients with anterior cruciate ligament injuries receiving arthroscopic surgeries. LSCs were obtained by collagenase digestion and plating as previously reported. Surface immunophenotype as well as tri-lineage differentiation potentials into osteoblasts, chondrocytes, and adipocytes were confirmed. It was found that proliferation of the cells was enhanced with the addition of FGF-2 and TGF-b1. Upon TGF-b1 treatment, expression of collagen type I and type III, tenascin-c, fibronectin, and a-smooth muscle actin were significantly up-regulated. Additionally, LSCs treated with TGF-b1 and FGF-2 increased the production of collagenous and non-collagenous extracellular matrix protein. Together, these results demonstrate that LSCs respond differently to various cytokines, and the results further validate the potential of using cruciate ligament tissue as a stem cell source for tissue engineering purpose.
FIBROBLAST GROWTH FACTOR-2 ENHANCES PROLIFERATION AND DELAYS LOSS OF CHONDROGENIC POTENTIAL IN HUMAN ADULT BONE MARROW-DERIVED MESENCHYMAL STEM CELLS.
Solchaga LA, Penick K, Goldberg VM, Caplan AI, Welter JF.
Case Western Reserve University, General Medical Sciences: Hematology and Oncology, Cleveland, Ohio, United States, 1-216-368-4077; [email protected].
We compared human mesenchymal stem cells (hMSCs), expanded long-term with and without fibroblast growth factor (FGF) supplementation, with respect to proliferation, and ability to undergo chondrogenesis in vitro. hMSCs expanded in FGF-supplemented medium proliferated more rapidly than control cells. Aggregates of FGF-treated cells exhibited chondrogenic differentiation at all passages tested although, in some preparations, differentiation was diminished after seventh passage. Aggregates made with control cells differentiated along the chondrogenic lineage after first passage but exhibited only marginal differentiation after fourth and failed to form cartilage after seventh passage. Microarray analysis of gene expression identified 334 transcripts differentially expressed in fourth passage control cells which had reduced chondrogenic potential, compared to fourth passage FGF-treated cells which retained this capacity, and 243 transcripts that were differentially expressed when comparing them to first passage control cells which were also capable of differentiating into chondrocytes. The intersection of these analyses yielded 49 transcripts differentially expressed in cells that exhibited chondrogenic differentiation in vitro compared to cells that did not. Among these, ANGPT1, SFRP1 and STEAP1 appear to be of higher relevance. These preliminary data must now be validated to verify whether different gene expression profiles translate into functional differences. In sum, these findings suggest that the chondrogenic potential of hMSCs is vulnerable to cell expansion and that care should be exercised when expanding these cells for cartilage tissue engineering applications. Supplementation with FGF-2 allows reaching target cell numbers more rapidly and extends the level of expansion within which these cells are useful for tissue-engineered cartilage repair.
Arthroscopy. 2009 Jun;25(6):608-16. Epub 2009 Jan 24.
The effects of fibroblast growth factor-2 on rotator cuff reconstruction with acellular dermal matrix grafts.
Ide J, Kikukawa K, Hirose J, Iyama K, Sakamoto H, Mizuta H.
Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. [email protected]
PURPOSE: Our purpose was to determine whether the local application of fibroblast growth factor (FGF) 2 accelerates regeneration and remodeling of rotator cuff tendon defects reconstructed with acellular dermal matrix (ADM) grafts in rats. METHODS: Thirty adult male Sprague-Dawley rats were divided into equal groups undergoing FGF-treated and FGF-untreated repairs. All rats underwent placement of an ADM graft for the supraspinatus defect (3 x 5 mm). FGF-2 (100 microg/kg) in a fibrin sealant was applied to both shoulders in the FGF-treated group, whereas only fibrin sealant was applied in untreated group. At 2, 6, and 12 weeks after surgery, 5 rats (10 shoulders) in each group were sacrificed for histologic analysis (3 shoulders) and biomechanical testing (7 shoulders). The controls were 5 unoperated rats (3 histologic and 7 biomechanical control specimens). RESULTS: Unoperated control tendons inserted into the bone by direct insertion; there was a zone of fibrocartilage between the tendon and bone. At 2 weeks, the FGF-treated group had tendon maturing scores similar to those in the untreated group (P > .05). At 6 and 12 weeks, the FGF-treated group had significantly higher scores (P < .05). At 2 weeks, specimens in both the treated and untreated groups exhibited similar strength; the ultimate tensile failure load was 6.0 +/- 4.0 N and 5.8 +/- 2.0 N, respectively (P > .05). At 6 weeks, the FGF-treated specimens were stronger, with an ultimate tensile failure load of 10.2 +/- 3.1 N compared with 7.2 +/- 2.2 N in the untreated group (P = .02). At 12 weeks, the FGF-treated specimens were stronger, with an ultimate tensile failure load of 15.9 +/- 1.6 N compared with 13.2 +/- 2.0 N in the untreated group (P = .0072), and there were no significant differences in strength compared with the controls (17.8 +/- 2.6 N) (P > .05). CONCLUSIONS: The remodeling of ADM grafts placed in rat rotator cuff tendon defects was accelerated by the local administration of FGF-2. CLINICAL RELEVANCE: The application of FGF-2 may result in improved histologic characteristics and biomechanical strength in ADM graft constructs in humans.
Tissue Eng Part A. 2009 Jul 8. [Epub ahead of print]
Modulation of proliferation and differentiation of human anterior cruciate ligament derived stem cells by different growth factors.
Cheng MT, Yang HW, Chen TH, Lee OK.
National Yang-Ming University, Institute of Clinical Medicine, Taipei, Taiwan; [email protected].
We have previously isolated and identified stem cells from human cruciate ligaments. The goal of this study is to evaluate the proliferation and differentiation abilities of ligament-derived stem cells (LSCs) cultured with growth factors including fibroblast growth factor 2 (FGF-2), epidermal growth factor (EGF), and transforming growth factor-beta 1 (TGF-b1). The ligament tissues were obtained from patients with anterior cruciate ligament injuries receiving arthroscopic surgeries. LSCs were obtained by collagenase digestion and plating as previously reported. Surface immunophenotype as well as tri-lineage differentiation potentials into osteoblasts, chondrocytes, and adipocytes were confirmed. It was found that proliferation of the cells was enhanced with the addition of FGF-2 and TGF-b1. Upon TGF-b1 treatment, expression of collagen type I and type III, tenascin-c, fibronectin, and a-smooth muscle actin were significantly up-regulated. Additionally, LSCs treated with TGF-b1 and FGF-2 increased the production of collagenous and non-collagenous extracellular matrix protein. Together, these results demonstrate that LSCs respond differently to various cytokines, and the results further validate the potential of using cruciate ligament tissue as a stem cell source for tissue engineering purpose.
