Expansion and Characterization of Human Embryonic Stem Cell-Derived Osteoblast-Like Cells

Arpornmaeklong, Premjit; Wang, Zhuo; Pressler, Michael J.; Brown, Shelley E.; Krebsbach, Paul H.

doi:10.1089/cell.2009.0079

Cited by 26 publications

(31 citation statements)

References 48 publications

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“…In vitro osteogenic differentiation of primary osteoblasts [8][9][10][11][12][13]44] and ESCs [17][18][19][20][21] have both been well described, but there have been few comparative studies. In this study, both cell types showed expression of markers indicative of osteogenic differentiation and formed nodules comprising Values corrected to proportion of osteogenic control.…”

Section: Discussionmentioning

confidence: 99%

“…Both mouse [17,18] and human ESCs [19][20][21] have been shown to display the features of osteogenically differentiated cells in vitro, exhibiting molecular and structural features resembling bone tissue by the formation of mineralized bone nodule structures. The majority of osteogenic protocols for ESCs direct cell differentiation by including factors in the culture medium, such as b-glycerophosphate (BGP), ascorbate, dexamethasone, simvastatin, retinoic acid, vitamin D 3 , and bone morphogenic proteins [3,[22][23][24][25][26][27][28][29][30].…”

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confidence: 99%

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Comparison of Osteogenic Differentiation of Embryonic Stem Cells and Primary Osteoblasts Revealed by Responses to IL-1β, TNF-α, and IFN-γ

Sidney

Kirkham

Buttery

2014

Stem Cells and Development

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There are well-established approaches for osteogenic differentiation of embryonic stem cells (ESCs), but few show direct comparison with primary osteoblasts or demonstrate differences in response to external factors. Here, we show comparative analysis of in vitro osteogenic differentiation of mouse ESC (osteo-mESC) and mouse primary osteoblasts. Both cell types formed mineralized bone nodules and produced osteogenic extracellular matrix, based on immunostaining for osteopontin and osteocalcin. However, there were marked differences in the morphology of osteo-mESCs and levels of mRNA expression for osteogenic genes. In response to the addition of proinflammatory cytokines interleukin-1b, tumor necrosis factor-a, and interferon-g to the culture medium, primary osteoblasts showed increased production of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) at early time points and decreases in cell viability. In contrast, osteo-mESCs maintained viability and did not produce NO and PGE 2 until day 21. The formation of bone nodules by primary osteoblasts was reduced markedly after cytokine stimulation but was unaffected in osteo-mESCs. Cell sorting of osteo-mESCs by cadherin-11 (cad-11) showed clear osteogenesis of cad-11+ cells compared to unsorted osteo-mESCs and cad-11 -cells. Moreover, the cad-11 + cells showed a significant response to cytokines, similar to primary osteoblasts. Overall, these results show that while osteo-mESC cultures, without specific cell sorting, show characteristics of osteoblasts, there are also marked differences, notably in their responses to cytokine stimuli. These findings are relevant to understanding the differentiation of stem cells and especially developing in vitro models of disease, testing new drugs, and developing cell therapies.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Comparison of Osteogenic Differentiation of Embryonic Stem Cells and Primary Osteoblasts Revealed by Responses to IL-1β, TNF-α, and IFN-γ

Sidney

Kirkham

Buttery

2014

Stem Cells and Development

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“…20 Previous to implantation, the differentiation conditions for committing MAPCs to osteoprogenitor cells in vitro have required long culture periods, as in differentiation of human embryonic stem cells into mesenchymal Color images available online at www.liebertpub.com/tea precursors. 5,[40][41][42] However, to satisfy the demand of high osteoprogenitor cell numbers to regenerate large skeletal defects via a tissue-engineered approach, novel aggregate culture conditions were used here to assure a consistent MAPC osteogenic differentiation on a large scale. 17 More than 1000 progenitor cells/cm 3 have been required for bone healing to occur.…”

Section: Discussionmentioning

confidence: 99%

Titanium-Enriched Hydroxyapatite–Gelatin Scaffolds with Osteogenically Differentiated Progenitor Cell Aggregates for Calvaria Bone Regeneration

Ferreira

Padilla

Urkasemsin

et al. 2013

Tissue Engineering Part A

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Adequate bony support is the key to re-establish both function and esthetics in the craniofacial region. Autologous bone grafting has been the gold standard for regeneration of problematic large bone defects. However, poor graft availability and donor-site complications have led to alternative bone tissue-engineering approaches combining osteoinductive biomaterials and three-dimensional cell aggregates in scaffolds or constructs. The goal of the present study was to generate novel cell aggregate-loaded macroporous scaffolds combining the osteoinductive properties of titanium dioxide (TiO 2 ) with hydroxyapatite-gelatin nanocomposites (HAP-GEL) for regeneration of craniofacial defects. Here we investigated the in vivo applicability of macroporous (TiO 2 )-enriched HAP-GEL scaffolds with undifferentiated and osteogenically differentiated multipotent adult progenitor cell (MAPC and OD-MAPC, respectively) aggregates for calvaria bone regeneration. The silane-coated HAP-GEL with and without TiO 2 additives were polymerized and molded to produce macroporous scaffolds. Aggregates of the rat MAPC were precultured, loaded into each scaffold, and implanted to rat calvaria criticalsize defects to study bone regeneration. Bone autografts were used as positive controls and a poly(lacticco-glycolic acid) (PLGA) scaffold for comparison purposes. Preimplanted scaffolds and calvaria bone from pig were tested for ultimate compressive strength with an Instron 4411 Ò and for porosity with microcomputerized tomography (mCT). Osteointegration and newly formed bone (NFB) were assessed by mCT and nondecalcified histology, and quantified by calcium fluorescence labeling. Results showed that the macroporous TiO 2 -HAP-GEL scaffold had a comparable strength relative to the natural calvaria bone (13.8 -4.5 MPa and 24.5 -8.3 MPa, respectively). Porosity was 1.52 -0.8 mm and 0.64 -0.4 mm for TiO 2 -HAP-GEL and calvaria bone, respectively. At 8 and 12 weeks postimplantation into rat calvaria defects, greater osteointegration and NFB were significantly present in the TiO 2 -enriched HAP-GEL constructs with OD-MAPCs, compared to the undifferentiated MAPCloaded constructs, cell-free HAP-GEL with and without titanium, and PLGA scaffolds. The tissue-engineered TiO 2 -enriched HAP-GEL constructs with OD-MAPC aggregates present a potential useful therapeutic approach for calvaria bone regeneration.

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“…There are reports of attempts to generate osteo-and chondroprogenitors (also known as bone marrow-derived mesenchymal stem cells [MSCs]) from embryonic stem cells (ESCs) [1][2][3][4][5][6][7][8][9][10] and iPSCs [11][12][13][14]. However, there are three broad limitations in performing these types of studies.…”

Section: Introductionmentioning

confidence: 99%

“…Studies reliant on EBs are limited by variability and substitute a black box for a true mechanistic understanding of differentiation processes. Third, although bone formation can be assayed with great specificity by in vivo transplantation, many studies that do so are limited by an incomplete collection or presentation of data or analysis of the results [5,10,13,[18][19][20][21][22][23][24]. Thus, reports on the formation of bone or cartilage from donor cells are sometimes premature based on the evidence presented.…”

Section: Introductionmentioning

confidence: 99%

Directed Differentiation of Human Induced Pluripotent Stem Cells Toward Bone and Cartilage: In Vitro Versus In Vivo Assays

Phillips

Kuznetsov

Cherman

et al. 2014

Stem Cells Translational Medicine

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The ability to differentiate induced pluripotent stem cells (iPSCs) into committed skeletal progenitors could allow for an unlimited autologous supply of such cells for therapeutic uses; therefore, we attempted to create novel bone-forming cells from human iPSCs using lines from two distinct tissue sources and methods of differentiation that we previously devised for osteogenic differentiation of human embryonic stem cells, and as suggested by other publications. The resulting cells were assayed using in vitro methods, and the results were compared with those obtained from in vivo transplantation assays. Our results show that true bone was formed in vivo by derivatives of several iPSC lines, but that the successful cell lines and differentiation methodologies were not predicted by the results of the in vitro assays. In addition, bone was formed equally well from iPSCs originating from skin or bone marrow stromal cells (also known as bone marrow-derived mesenchymal stem cells), suggesting that the iPSCs did not retain a "memory" of their previous life. Furthermore, one of the iPSC-derived cell lines formed verifiable cartilage in vivo, which likewise was not predicted by in vitro assays. STEM CELLS

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Expansion and Characterization of Human Embryonic Stem Cell-Derived Osteoblast-Like Cells

Cited by 26 publications

References 48 publications

Comparison of Osteogenic Differentiation of Embryonic Stem Cells and Primary Osteoblasts Revealed by Responses to IL-1β, TNF-α, and IFN-γ

Comparison of Osteogenic Differentiation of Embryonic Stem Cells and Primary Osteoblasts Revealed by Responses to IL-1β, TNF-α, and IFN-γ

Titanium-Enriched Hydroxyapatite–Gelatin Scaffolds with Osteogenically Differentiated Progenitor Cell Aggregates for Calvaria Bone Regeneration

Directed Differentiation of Human Induced Pluripotent Stem Cells Toward Bone and Cartilage: In Vitro Versus In Vivo Assays

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