Growth factor combination for chondrogenic induction from human mesenchymal stem cell

Indrawattana, Nitaya; Chen, Guoping; Tadokoro, Mika; Shann, Linzi H; Ohgushi, Hajime; Tateishi, Tetsuya; Tanaka, Junzo; Bunyaratvej, Ahnond

doi:10.1016/j.bbrc.2004.06.029

Cited by 386 publications

(263 citation statements)

References 22 publications

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“…In stark contrast to findings in previously reported studies in which BMP-6 was used to induce chondrogenesis (24,28,30), the results of this study demonstrate that BMP-6 not only is a strong inducer of 2 primary chondrogenic markers, AGC1 and COL2A1, but also is a strong inhibitor of the hypertrophic/ endochondral ossification pathway, as indicated by significant decreases in COL10A1 gene expression and immunolabeling compared with other chondrogenic conditions (Figures 4 and 5). It is possible that a longer time course of study would reveal an increase in COL10A1 gene expression with BMP-6, as has been observed with other cell types (39,45).…”

Section: Discussioncontrasting

confidence: 99%

“…In a similar cell pellet culture system, the addition of BMP-6 to TGF␤3 and dexamethasone resulted in a significant increase in pellet mass (10-fold) and in COL2A1 and COL10A1 gene expression over the 21-day culture period compared with control treatment, TGF␤3 plus dexamethasone, or BMP-6 alone (28). In other studies on MSCs, IGF-1 or BMP-6 acted in a synergistic manner with TGF␤3 to promote chondrogenesis of MSCs, but BMP-6 alone was unable to induce chondrogenesis (24). In periosteal grafts containing MSCs capable of osteogenic and chondrogenic differentiation, IGF-1 can act in a synergistic manner with TGF␤1 for chondrogenic differentiation as measured by type II collagen messenger RNA (mRNA) levels (31).…”

mentioning

confidence: 81%

“…The concentrations of TGF␤1, TGF␤3, and IGF-1 used for chondrogenic differentiation were based on previous studies of MSCs and ADAS cells (13)(14)(15)17,18,21,(24)(25)(26)(27)(28)30,31). To determine the dose-response effect of BMP-6, the effects of BMP-6 at a range of concentrations (5-500 ng/ml) on the expression of COL1A1, COL2A1, COL10A1, and AGC1 gene transcripts were examined, showing maximum stimulation of COL2A1 and AGC1 and suppression of COL10A1 at 500 ng/ml.…”

Section: Methodsmentioning

confidence: 99%

“…These cells also can be induced toward a chondrogenic phenotype with growth factors including insulin-like growth factor 1 (IGF-1), TGF␤2, and bone morphogenetic protein 6 (BMP-6), in addition to TGF␤1 and TGF␤3 (23)(24)(25)(26)(27)(28)(29)(30)(31). Results of previous studies suggest that TGF␤2 and TGF␤3 are more effective than TGF␤1 in promoting glycosaminoglycan and type II collagen accumulation in micromass pellet culture (25).…”

mentioning

confidence: 99%

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Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

Estes

Guilak

2006

Arthritis & Rheumatism

271

212

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Objective. Recent studies have identified an abundant source of multipotent progenitor cells in subcutaneous human adipose tissue, termed human adiposederived adult stem cells (ADAS cells). In response to specific media formulations, including transforming growth factor ␤1 (TGF␤1), these cells exhibit significant ability to differentiate into a chondrocyte-like phenotype, expressing cartilage-specific genes and proteins such as aggrecan and type II collagen. However, the influence of other growth factors on the chondrogenic differentiation of ADAS cells is not fully understood. This study was undertaken to investigate the effects of TGF␤1, TGF␤3, insulin-like growth factor 1, bone morphogenetic protein 6 (BMP-6), and dexamethasone, in various combinations, on the chondrogenic potential of ADAS cells in alginate beads.Methods. The chondrogenic response of alginateencapsulated ADAS cells was measured by quantitative polymerase chain reaction, 3 H-proline and 35 S-sulfate incorporation, and immunolabeling for specific extracellular matrix components.Results. Significant differences in chondrogenesis were observed under the different culture conditions for all outcomes measured. Most notably, BMP-6 upregulated AGC1 and COL2A1 expression by an average of 205-fold and 38-fold, respectively, over day-0 controls, while down-regulating COL10A1 expression by ϳ2-fold.Conclusion. These findings suggest that BMP-6 is a potent inducer of chondrogenesis in ADAS cells, in contrast to mesenchymal stem cells, which exhibit increased expression of type X collagen and a hypertrophic phenotype in response to BMP-6. Combinations of growth factors containing BMP-6 may provide a novel means of regulating the differentiation of ADAS cells for applications in the tissue-engineered repair or regeneration of articular cartilage.

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Section: Discussioncontrasting

confidence: 99%

mentioning

confidence: 81%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

Estes

Guilak

2006

Arthritis & Rheumatism

271

212

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“…Strong cell-cell interaction mediated by cell adhesion molecules such as N-cadherin and integrins allow MSC conversion to prechondroblasts at the precartilage mesenchymal condensation stage during limb development (Haas and Tuan, 1999;Hall and Miyake, 1995). Various bioactive factors, such as fibroblast growth factor, transforming growth factors (TGF) b1 and b3, bone morphogenic proteins (BMPs)-2, -6, and -9, and insulin-like growth factors, have been reported to induce or maintain chondrogenesis (Indrawattana et al, 2004;Muraglia et al, 2000;Sekiya et al, 2002).…”

Section: Introductionmentioning

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

444

322

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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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Low‐Intensity Ultrasound in Stem Cells and Tissue Engineering

Choi

Kim

Karmacharya

et al. 2014

Cell and Molecular Biology and Imaging of Stem Cells

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Growth factor combination for chondrogenic induction from human mesenchymal stem cell

Cited by 386 publications

References 22 publications

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

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

Low‐Intensity Ultrasound in Stem Cells and Tissue Engineering

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