Growth and differentiation of human bone marrow osteoprogenitors on novel calcium phosphate cements

Oreffo, Richard O.C.; Driessens, F. C. M.; Planell, Josep A.; Triffitt, James T.

doi:10.1016/s0142-9612(98)00084-2

Cited by 110 publications

(78 citation statements)

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“…Various in vitro bone regeneration strategies have relied on the use of the osteogenic supplements (dexamethasone, ascorbic acid, and b-glycerophosphate) to induce mineralization in vitro, 12,13,49,51,[53][54][55][56][57][58][59][60][61][62] and each supplement has been shown to be imperative to induce mineralization of MSCs in vitro. 9,[11][12][13][14][15][16][17]22,29,[63][64][65][66][67] The main rationale behind the use of these supplements is to provide signaling proteins or enzymes to activate mineral production by MSCs.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Freeman

Stevens

Owens

et al. 2016

Tissue Engineering Part A

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In vitro bone regeneration strategies that prime mesenchymal stem cells (MSCs) with chondrogenic factors, to mimic aspects of the endochondral ossification process, have been shown to promote mineralization and vascularization by MSCs both in vitro and when implanted in vivo. However, these approaches required the use of osteogenic supplements, namely dexamethasone, ascorbic acid, and b-glycerophosphate, none of which are endogenous mediators of bone formation in vivo. Rather MSCs, endothelial progenitor cells, and chondrocytes all reside in proximity within the cartilage template and might paracrineally regulate osteogenic differentiation. Thus, this study tests the hypothesis that an in vitro bone regeneration approach that mimics the cellular niche existing during endochondral ossification, through coculture of MSCs, endothelial cells, and chondrocytes, will obviate the need for extraneous osteogenic supplements and provide an alternative strategy to elicit osteogenic differentiation of MSCs and mineral production. The specific objectives of this study were to (1) mimic the cellular niche existing during endochondral ossification and (2) investigate whether osteogenic differentiation could be induced without the use of any external growth factors. To test the hypothesis, we evaluated the mineralization and vessel formation potential of (a) a novel methodology involving both chondrogenic priming and the coculture of human umbilical vein endothelial cells (HUVECs) and MSCs compared with (b) chondrogenic priming of MSCs alone, (c) addition of HUVECs to chondrogenically primed MSC aggregates, (d-f) the same experimental groups cultured in the presence of osteogenic supplements and (g) a noncoculture group cultured in the presence of osteogenic growth factors alone. Biochemical (DNA, alkaline phosphatase [ALP], calcium, CD31 + , vascular endothelial growth factor [VEGF]), histological (alcian blue, alizarin red), and immunohistological (CD31 + ) analyses were conducted to investigate osteogenic differentiation and vascularization at various time points (1, 2, and 3 weeks). The coculture methodology enhanced both osteogenesis and vasculogenesis compared with osteogenic differentiation alone, whereas osteogenic supplements inhibited the osteogenesis and vascularization (ALP, calcium, and VEGF) induced through coculture alone. Taken together, these results suggest that chondrogenic and vascular priming can obviate the need for osteogenic supplements to induce osteogenesis of human MSCs in vitro, while allowing for the formation of rudimentary vessels.

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Section: Discussionmentioning

confidence: 99%

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Freeman

Stevens

Owens

et al. 2016

Tissue Engineering Part A

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“…Cell culture studies indicated that there was no significant limitation in cell viability after 1 week of exposure to FeHA when compared to pure HA. The initial decrease in cell viability at days 1 and 3 may be due to the fact that although HA is biocompatible, some recent studies have shown that calcium phosphates can have an inhibitory effect on osteoblast in vitro [33][34][35]. Although in vitro cell culture studies are useful tools for initial-stage biological screening of biomaterials, behavior in vivo is completely different.…”

Section: Discussionmentioning

confidence: 99%

A Comparative Study of the Sintering Behavior of Pure and Iron-Substituted Hydroxyapatite

Kramer¹,

Zilm²,

Wei³

2013

Bioceram Dev Appl

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Hydroxyapatite (HA) is a widely studied biomaterial for bone grafting and tissue engineering applications. The crystal structure of HA lends itself to a wide variety of substitutions, which allows for tailoring of material properties. Iron is of interest in ion substitution in HA due to its magnetic properties. The synthesis and characterization of iron-substituted hydroxyapatite (FeHA) have been widely studied, but there is a lack of studies on the sintering behaviors of FeHA materials compared to pure HA. Studying the sintering behavior of a substituted apatite provides information regarding how the substitution affects material characteristics such as stability and bulk mechanical properties, thereby providing insight into which applications are appropriate for the substituted material. In this study both pure HA and FeHA were synthesized, pressed into pellets, and then sintered at temperatures ranging from 900-1300°C and 600-1100°C, respectively. The study thoroughly examined the comparative sintering behaviors of the two materials using density measurements, mechanical testing, X-ray diffraction, and electron microscopy. It was found that FeHA is considerably less thermally stable than pure HA, with decomposition beginning around 1200°C for pure HA samples, while at 700°C for the FeHA. The FeHA also had a much lower mechanical strength than that of the pure HA. An in vitro cell culture study was conducted by immersing FeHA powder in cell culture media, with HA powder at equivalent doses as a control, verified that FeHA is a biocompatible material. Although the FeHA would be unsuitable for bulk applications, it is a potential material for a variety of biomedical applications including drug delivery, cancer hyperthermia, and bone tissue engineering composites.

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“…These were based on the utilization of supports, as gels and sponges of collagen type I, PLGA foam, DegraPol, agarose, Matrigel, or methylcellulose. 7,10,15,16,18,20,22,25,26,30,32,34,37,39 Normal human osteogenic cells, osteoblasts from prepubertal-age donors, or bone marrow stromal fibroblasts adhering to scaffolding of HAP/ TC, 16,20,25,26,30,34 collagraft, 26 collagen sponges, 15,39 or bone chips 5 were utilized to produce specifically 3D structures designed for direct implantation in vivo.…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional cultures of normal human osteoblasts: proliferation and differentiation potential in vitro and upon ectopic implantation in nude mice

Ferrera

Poggi

Biassoni

et al. 2002

Bone

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Growth and differentiation of human bone marrow osteoprogenitors on novel calcium phosphate cements

Cited by 110 publications

References 0 publications

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

A Comparative Study of the Sintering Behavior of Pure and Iron-Substituted Hydroxyapatite

Three-dimensional cultures of normal human osteoblasts: proliferation and differentiation potential in vitro and upon ectopic implantation in nude mice

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