Combined effects of insulin-like growth factor-1 and transforming growth factor-β1 on periosteal mesenchymal cells during chondrogenesis in vitro

Fukumoto, Tetsuya; Sperling, Jens; Sanyal, Abhik Kumar; Fitzsimmons, James S.; Reinholz, Gregory G.; Conover, Cheryl A.; O’Driscoll, Shawn W.

doi:10.1053/joca.2002.0869

Cited by 237 publications

(171 citation statements)

References 62 publications

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“…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%

“…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: 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).…”

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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: Methodsmentioning

confidence: 99%

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confidence: 99%

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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“…Factors influencing cell phenotype include sex steroids [41,43], endogenous growth factors [26,45] and mechanical loading environment in vivo [27,42], and isolation [30], culture methods [8,13,20,31,37] and the donor site [14] in vitro. Lim [24] identified potential precursor populations within periosteal cultures.…”

Section: Introductionmentioning

confidence: 99%

Human Periosteum Is a Source of Cells for Orthopaedic Tissue Engineering: A Pilot Study

Ball

Bonzani

Bovis

et al. 2011

Clinical Orthopaedics &Amp; Related Research

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Background Periosteal cells are important in embryogenesis, fracture healing, and cartilage repair and could provide cells for osteochondral tissue engineering. Questions/purpose We determined whether a population of cells isolated from human periosteal tissue contains cells with a mesenchymal stem cell (MSC) phenotype and whether these cells can be expanded in culture and used to form tissue in vitro. Methods We obtained periosteal tissue from six patients. Initial expression of cell surface markers was assessed using flow cytometry. Cells were cultured over 10 generations and changes in gene expression evaluated to assess phenotypic stability. Phenotype was confirmed using flow cytometry and colony-forming ability assays. Mineral formation was assessed by culturing Stro-1 À and unsorted cells with osteogenic supplements. Three cell culture samples were used for a reverse transcription-polymerase chain reaction, four for flow cytometry, three for colony-forming assay, and three for mineralization. Results Primary cultures, containing large numbers of hematopoietic cells were replaced initially by Stro-1 and ALP-expressing immature osteoblastic cell types and later by ALP-expressing cells, which lacked Stro-1 and which became the predominant cell population during subculture.

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“…There are increasing reports that MSCs can be isolated from various adult mesenchymal tissues such as synovium (5), periosteum (6), skeletal muscle (7), and adipose tissue (8) in addition to bone marrow (9). These MSCs have been assumed to be similar irrespective of their original tissue source since they all have self-renewal and multidifferentiation potential with common surface epitopes (10,11).…”

mentioning

confidence: 99%

Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source

Sakaguchi¹,

Sekiya²,

Yagishita³

et al. 2005

Arthritis & Rheumatism

1,375

1,171

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Objective. To compare the properties of human mesenchymal stem cells (MSCs) isolated from bone marrow, synovium, periosteum, skeletal muscle, and adipose tissue.Methods. Human mesenchymal tissues were obtained from 8 donors during knee surgery for ligament injury. After collagenase digestion or gradient-density separation, nucleated cells were plated at an appropriate density for expansion at the maximum rate without colony-to-colony contact. Yield, expandability, differentiation potential, and epitope profile were compared among MSCs from the 5 different tissue sources.Results. Colony number per 10 3 nucleated cells was lower, and cell number per colony was higher, in bone marrow than in other mesenchymal tissues. When the cells were replated at low density every 14 days, bone marrow-, synovium-, and periosteum-derived cells retained their proliferation ability even at passage 10. In chondrogenesis studies in which the cells were pelleted and cultured in vitro, pellets from bone marrow-, synovium-, and periosteum-derived cells were shown to be larger and stained more extensively for cartilage matrix. Synovium-derived cells, in particular, had the greatest ability for chondrogenesis. In adipogenesis experiments, the frequency of oil red O-positive colonies was highest in synovium-and adipose tissue-derived cells. In studies of osteogenesis, the rate of alizarin red-positive colonies was highest in bone marrow-, synovium-, and periosteum-derived cells. For epitope profiling, 15 surface antigens were measured. Most appeared to have similar epitope profiles irrespective of cell source.Conclusion. Our findings indicate that there are significant differences in MSC properties according to tissue source, beyond donor and experimental variation. Superiority of synovium as a potential source of MSCs for clinical applications was demonstrated.

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Combined effects of insulin-like growth factor-1 and transforming growth factor-β1 on periosteal mesenchymal cells during chondrogenesis in vitro

Abstract: The results of this study demonstrate that IGF-1 and TGF-beta1 can act in combination to regulate proliferation and differentiation of periosteal mesenchymal cells during chondrogenesis.

Cited by 237 publications

References 62 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

Human Periosteum Is a Source of Cells for Orthopaedic Tissue Engineering: A Pilot Study

Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source

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