A 3D <i>ex vivo</i> mandible slice system for longitudinal culturing of transplanted dental pulp progenitor cells

Colombo, John S.; Howard-Jones, Rachel Anne; Young, Fraser; Waddington, Rachel J.; Errington, Rachel J.; Sloan, Alastair James

doi:10.1002/cyto.a.22680

Cited by 9 publications

(12 citation statements)

References 40 publications

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“…This is consistent with uninjected mandible slices (Appendix Fig. 1C) and with previously published results of uninjected mandible slices (Smith et al 2010;Sloan et al 2013;Roberts et al 2013;Colombo et al 2015).…”

Section: Histologysupporting

confidence: 93%

Ex Vivo Modeling of Multidomain Peptide Hydrogels with Intact Dental Pulp

et al. 2015

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Preservation of a vital dental pulp is a central goal of restorative dentistry. Currently, there is significant interest in the development of tissue engineering scaffolds that can serve as biocompatible and bioactive pulp-capping materials, driving dentin bridge formation without causing cytotoxic effects. Our earlier in vitro studies described the biocompatibility of multidomain peptide (MDP) hydrogel scaffolds with dental pulp-derived cells but were limited in their ability to model contact with intact 3-dimensional pulp tissues. Here, we utilize an established ex vivo mandible organ culture model to model these complex interactions. MDP hydrogel scaffolds were injected either at the interface of the odontoblasts and the dentin or into the pulp core of mandible slices and subsequently cultured for up to 10 d. Histology reveals minimal disruption of tissue architecture adjacent to MDP scaffolds injected into the pulp core or odontoblast space. Additionally, the odontoblast layer is structurally preserved in apposition to the MDP scaffold, despite being separated from the dentin. Alizarin red staining suggests mineralization at the periphery of MDP scaffolds injected into the odontoblast space. Immunohistochemistry reveals deposition of dentin sialophosphoprotein by odontoblasts into the adjacent MDP hydrogel, indicating continued functionality. In contrast, no mineralization or dentin sialophosphoprotein deposition is evident around MDP scaffolds injected into the pulp core. Collagen III expression is seen in apposition to gels at all experimental time points. Matrix metalloproteinase 2 expression is observed associated with centrally injected MDP scaffolds at early time points, indicating proteolytic digestion of scaffolds. Thus, MDP scaffolds delivered centrally and peripherally within whole dental pulp tissue are shown to be biocompatible, preserving local tissue architecture. Additionally, odontoblast function and pulp vitality are sustained when MDP scaffolds are intercalated between dentin and the odontoblast region, a finding that has significant implications when considering these materials as pulp-capping agents.

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Section: Histologysupporting

confidence: 93%

Ex Vivo Modeling of Multidomain Peptide Hydrogels with Intact Dental Pulp

et al. 2015

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“… 16 This method was later modified to include the use of green fluorescent protein (GFP) expressing DPSCs, enabling the visualisation of transplanted cells following injection into ex vivo mandible slice. 17 Although much of the work on DPSCs has been completed using monolayer culture systems, there is a fundamental need to better understand how these cells behave in a three-dimensional system, providing a more accurate reflection of their in vivo characteristics.…”

Section: Methodsmentioning

confidence: 99%

“… 16 This model was adapted by Colombo and colleagues to enable the study of dental pulp stem cell (DPSC) behaviour in an ex vivo environment. 17 DPSCs have characteristics similar to mesenchymal stem cells 18 19 and display migratory and odontoblast differentiation capacity in response to tissue damage. 19 20 21 Studying DPSC behaviour in an ex vivo mandible slice enables understanding of their multi-potency and how they may initiate bone repair in response to injury (Method 4).…”

Section: Introductionmentioning

confidence: 99%

Models of ex vivo explant cultures: applications in bone research

Marino¹,

Staines²,

Brown³

et al. 2016

BoneKEy Reports

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Ex vivo explant culture models are powerful tools in bone research. They allow investigation of bone and cartilage responses to specific stimuli in a controlled manner that closely mimics the in vivo processes. Because of limitations in obtaining healthy human bone samples the explant growth of animal tissue serves as a platform to study the complex physico-chemical properties of the bone. Moreover, these models enable preserving important cell–cell and cell–matrix interactions in order to better understand the behaviour of cells in their natural three-dimensional environment. Thus, the use of bone ex vivo explant cultures can frequently be of more physiological relevance than the use of two-dimensional primary cells grown in vitro. Here, we describe isolation and ex vivo growth of different animal bone explant models including metatarsals, femoral heads, calvaria, mandibular slices and trabecular cores. We also describe how these explants are utilised to study bone development, cartilage and bone metabolism, cancer-induced bone diseases, stem cell-driven bone repair and mechanoadaptation. These techniques can be directly used to understand mechanisms linked with bone physiology or bone-associated diseases.

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“…11-13 Therefore, the ex vivo biology system could be a good substitute for some in vivo and in vitro models in an experimental design which is relatively cost effective and ethically acceptable in terms of animal welfare. 14-16 …”

Section: Introductionmentioning

confidence: 99%

The use of rats and mice as animal models in ex vivo bone growth and development studies

Abubakar

Noordin

Azmi

et al. 2016

Bone & Joint Research

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In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine.Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610–618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2.

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A 3D ex vivo mandible slice system for longitudinal culturing of transplanted dental pulp progenitor cells

Cited by 9 publications

References 40 publications

Ex Vivo Modeling of Multidomain Peptide Hydrogels with Intact Dental Pulp

Ex Vivo Modeling of Multidomain Peptide Hydrogels with Intact Dental Pulp

Models of ex vivo explant cultures: applications in bone research

The use of rats and mice as animal models in ex vivo bone growth and development studies

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