A Recombinant Human TGF-β1 Fusion Protein with Collagen-Binding Domain Promotes Migration, Growth, and Differentiation of Bone Marrow Mesenchymal Cells

Andrades, José A.; Han, Bo; Becerra, José; Sorgente, Nino; Hall, Frederick L.; Nimni, Marcel E.

doi:10.1006/excr.1999.4528

Cited by 128 publications

(107 citation statements)

References 35 publications

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“…Cytokines such as vascular endothelial cell growth factors, TGFs, FGFs, plateletderived growth factors, monocyte chemoattractant protein-1, and IL-8 released from the neoplasm or inflammatory tissue are all possible candidates. 27,[30][31][32][33][34] It is known that these factors released from cancer cells promote the migration of endothelial cell and stromal cell progenitors from the bone marrow towards the cancer bed 35,36 or tissue surrounding the tumor, enhancing the formation of tumor-stroma. 37 Similar mechanisms would be anticipated for tumor-stromal formation in glioma, and for the migration of implanted MSCs.…”

Section: Discussionmentioning

confidence: 99%

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

et al. 2004

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The prognosis of patients with malignant glioma is extremely poor, despite the extensive surgical treatment that they receive and recent improvements in adjuvant radio-and chemotherapy. In the present study, we propose the use of gene-modified mesenchymal stem cells (MSCs) as a new tool for gene therapy of malignant brain neoplasms. Primary MSCs isolated from Fischer 344 rats possessed excellent migratory ability and exerted inhibitory effects on the proliferation of 9L glioma cell in vitro. We also confirmed the migratory capacity of MSCs in vivo and showed that when they were inoculated into the contralateral hemisphere, they migrated towards 9L glioma cells through the corpus callosum. MSCs implanted directly into the tumor localized mainly at the border between the 9L tumor cells and normal brain parenchyma, and also infiltrated into the tumor bed. Intratumoral injection of MSCs caused significant inhibition of 9L tumor growth and increased the survival of 9L glioma-bearing rats. Gene-modification of MSCs by infection with an adenoviral vector encoding human interleukin-2 (IL-2) clearly augmented the antitumor effect and further prolonged the survival of tumor-bearing rats. Thus, gene therapy employing MSCs as a targeting vehicle would be promising as a new therapeutic approach for refractory brain tumor.

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Section: Discussionmentioning

confidence: 99%

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

et al. 2004

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“…Our results showed that cells cultured in collagen type I hydrogel and in medium containing TGF b1, and dexamethasone expressed significantly high levels of coll 1 mRNA. MSCs undergo osteogenic differentiation upon treatment with dexamethasone or TGF b1, which is followed by increased expression of coll 1 mRNA (Andrades et al, 1999;Gronthos et al, 2003;Phinney et al, 1999). Damaged articular cartilage is usually substituted by fibrous cartilage of which collagen I is a component.…”

Section: Discussionmentioning

confidence: 99%

Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: Influence of collagen type II extracellular matrix on MSC chondrogenesis

Bosnakovski

Mizuno

Kim

et al. 2006

Biotech & Bioengineering

438

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Bone marrow mesenchymal stem cells (MSCs) are candidate cells for cartilage tissue engineering. This is due to their ability to undergo chondrogenic differentiation after extensive expansion in vitro and stimulation with various biomaterials in three-dimensional (3-D) systems. Collagen type II is one of the major components of the hyaline cartilage and plays a key role in maintaining chondrocyte function. This study aimed at analyzing the MSC chondrogenic response during culture in different types of extracellular matrix (ECM) with a focus on the influence of collagen type II on MSC chondrogenesis. Bovine MSCs were cultured in monolayer as well as in alginate and collagen type I and II hydrogels, in both serum free medium and medium supplemented with transforming growth factor (TGF) b1. Chondrogenic differentiation was detected after 3 days of culture in 3-D hydrogels, by examining the presence of glycosaminoglycan and newly synthesized collagen type II in the ECM. Differentiation was most prominent in cells cultured in collagen type II hydrogel, and it increased in a timedependent manner. The expression levels of the of chondrocyte specific genes: sox9, collagen type II, aggrecan, and COMP were measured by quantitative ''Real Time'' RT-PCR, and genes distribution in the hydrogel beads were localized by in situ hybridization. All genes were upregulated by the presence of collagen, particularly type II, in the ECM. Additionally, the chondrogenic influence of TGF b1 on MSCs cultured in collagenincorporated ECM was analyzed. TGF b1 and dexamethasone treatment in the presence of collagen type II provided more favorable conditions for expression of the chondrogenic phenotype. In this study, we demonstrated that collagen type II alone has the potential to induce and maintain MSC chondrogenesis, and prior interaction with TGF b1 to enhance the differentiation.

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“…Human dermal fibroblasts (HDF) were isolated from skin fragments discarded in surgical procedures for the six males adults donors and cultured to 80% confluence in DMEM (Sigma, St. Louis, MO, USA) containing 10% fetal bovine serum (FBS, Sigma, St. Louis, MO, USA), 1% penicillin, 100 U/streptomycin, and 100 mg/ml solution 10,11 , designated the standard culture medium. At this stage the adherent cells were detached (0.01% trypsin), counted in a Neubauer chamber, and seeded at a density of 2.5x10 4 cells/cm2 in 24-well plates containing collagen sponge discs (B. Braun, S.A., Germany) measuring 16x2 mm for 28 days under the following experimental conditions: CONTROL group, standard culture medium; TGF-β1 group, standard culture medium supplemented with 10 ng/ml TGF-β1 (Sigma); OSTEOG group, standard culture medium supplemented with 50 µg/ml ascorbic acid (Sigma), 10 mmol beta-glycerophosphate (Sigma), and 10 nmol of dexamethasone (Sigma); and OSTEOG.TGF-β1 group, standard culture medium supplemented with 50 µg/ml ascorbic acid, 10 mmol beta-glycerophosphate, 10 nmol dexamethasone, and 10 ng/ml TGF-β1 [18][19][20] .…”

Section: Cell Culturementioning

confidence: 99%

“…The presence of TGF-β1 influences bone tissue maintenance and development, in part by increasing the synthesis of the proteoglycan matrix and synthesis of collagen in the bone tissue 7,9,10 . Tissue engineering is also dependent on the use of signaling molecules that influence cell growth.…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 on induced osteogenic differentiation of human dermal fibroblast

et al. 2014

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PURPOSE:To evaluate the role of transforming growth factor beta 1 (TGF-β1) on the induced osteogenic differentiation of human dermal fibroblasts. METHODS:We performed four groups with cultured dermal fibroblasts according to the culture medium: CONTROL (DMEM culture medium); TGF-β1 (DMEM culture medium with 10 ng/ml of TGF-β1); OSTEOG (DMEM culture medium with 0.5 µg/ml of ascorbic acid, 10 mmol/l of β-glycerophosphate and 10 nmol/L of dexamethasone); and OSTEOG/TGF-β1 (osteogenic medium with 10 ng/ml of TGF-β1). Alkaline phosphatase (ALP) activity and the amount of osteocalcin (OC) in the supernatant, as well as the capability to form calcium phosphate deposits, were analysed for 28 days RESULTS: There were significant differences (p<0.05) between CONTROL and TGF-β1 groups in comparison with OSTEOG and OSTEOG/TGF-β1 groups in the ALP activity and OC amount. Although, both osteogenic groups had the same behavior with regard the expression curve during the experimental time, the OSTEOG/TGF-β1 group achieved significantly higher ALP and OC levels and showed no significant difference in the levels of mineralized deposits and in comparison with the levels found in the OSTEOG group. CONCLUSION:The addition of transforming growth factor beta 1 to the osteogenic culture medium increased the activity of alkaline phosphatase and the amount of osteocalcin, but TGF-β1 did not alter the presence of mineralized calcium phosphate deposits.

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A Recombinant Human TGF-β1 Fusion Protein with Collagen-Binding Domain Promotes Migration, Growth, and Differentiation of Bone Marrow Mesenchymal Cells

Cited by 128 publications

References 35 publications

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: Influence of collagen type II extracellular matrix on MSC chondrogenesis

TGF-β1 on induced osteogenic differentiation of human dermal fibroblast

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