Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials

Jeon, Ok Hee; Panicker, Leelamma M.; Lu, Qiaozhi; Chae, Jeremy J.; Feldman, Ricardo A.; Elisseeff, Jennifer H.

doi:10.1038/srep26761

Cited by 132 publications

(116 citation statements)

References 41 publications

(61 reference statements)

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“…Recently, several studies have produced bone-like matrix by seeding human PSCs on different 3D scaffolds [40–43] and using perfusion bioreactors [44, 45]. Jeon et al used a biomimetic approach to regenerate bone by 3D coculture of human PSC-derived osteoblasts and osteoclasts within a synthetic scaffolds [46]. We have recently developed protocols to direct the differentiation of hESCs to vascular cells [20, 47].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Osteogenic Potential of Green Fluorescent Protein Labelled Human Embryonic Stem Cell‐Derived Osteoprogenitors

Islam

Sriram

et al. 2016

Stem Cells International

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Cellular therapy using stem cells in bone regeneration has gained increasing interest. Various studies suggest the clinical utility of osteoprogenitors-like mesenchymal stem cells in bone regeneration. However, limited availability of mesenchymal stem cells and conflicting evidence on their therapeutic efficacy limit their clinical application. Human embryonic stem cells (hESCs) are potentially an unlimited source of healthy and functional osteoprogenitors (OPs) that could be utilized for bone regenerative applications. However, limited ability to track hESC-derived progenies in vivo greatly hinders translational studies. Hence, in this study, we aimed to establish hESC-derived OPs (hESC-OPs) expressing green fluorescent protein (GFP) and to investigate their osteogenic differentiation potential in vitro. We fluorescently labelled H9-hESCs using a plasmid vector encoding GFP. The GFP-expressing hESCs were differentiated into hESC-OPs. The hESC-OPsGFP+ stably expressed high levels of GFP, CD73, CD90, and CD105. They possessed osteogenic differentiation potential in vitro as demonstrated by increased expression of COL1A1, RUNX2, OSTERIX, and OPG transcripts and mineralized nodules positive for Alizarin Red and immunocytochemical expression of osteocalcin, alkaline phosphatase, and collagen-I. In conclusion, we have demonstrated that fluorescently labelled hESC-OPs can maintain their GFP expression for the long term and their potential for osteogenic differentiation in vitro. In future, these fluorescently labelled hESC-OPs could be used for noninvasive assessment of bone regeneration, safety, and therapeutic efficacy.

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Section: Discussionmentioning

confidence: 99%

In Vitro Osteogenic Potential of Green Fluorescent Protein Labelled Human Embryonic Stem Cell‐Derived Osteoprogenitors

Islam

Sriram

et al. 2016

Stem Cells International

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“…Another alternative can be represented by the use of human iPSCs (hiPSCs), which have been recently employed in bone TE for regenerative applications (TheinHan et al, 2013; Kang et al, 2014; Tang et al, 2014; Jeon et al, 2016; Ji et al, 2016). These cells may constitute an interesting cell source for the design of in vitro models of healthy and pathologic bone tissue.…”

Section: Bone In Vitro Modelsmentioning

confidence: 99%

Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

Caddeo

Boffito

Sartori

2017

Front. Bioeng. Biotechnol.

213

172

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In the tissue engineering (TE) paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D) microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix, the composition of which varies as a function of the tissue, the degree of maturation, and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D) models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the “3Rs” guiding principles for a more ethical research. The design of 3D engineered tissue models is currently in its development stage, showing high potential in overcoming the limitations of already available models. However, many issues are still opened, concerning the identification of the optimal scaffold-forming materials, cell source and biofabrication technology, and the best cell culture conditions (biochemical and physical cues) to finely replicate the native tissue and the surrounding environment. In the near future, 3D tissue-engineered models are expected to become useful tools in the preliminary testing and screening of drugs and therapies and in the investigation of the molecular mechanisms underpinning disease onset and progression. In this review, the application of TE principles to the design of in vitro 3D models will be surveyed, with a focus on the strengths and weaknesses of this emerging approach. In addition, a brief overview on the development of in vitro models of healthy and pathological bone, heart, pancreas, and liver will be presented.

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“…An attractive alternative to cell lines is bone cells derived from induced pluripotent stem cells (iPSCs). These would be the ideal resources for the necessary human cell studies and groups have already demonstrated that iPSCs can be used to derive osteoblasts 110 and osteoclasts 111 .…”

Section: Future Directionsmentioning

confidence: 99%

Using GWAS to identify novel therapeutic targets for osteoporosis

Sabik

Farber

2017

Translational Research

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Osteoporosis is a common, increasingly prevalent, global health burden characterized by low bone mineral density (BMD) and increased risk of fracture. Despite its significant impact on human health, there is currently a lack of highly effective treatments free of side effects for osteoporosis. Therefore, a major goal in the field is to identify new drug targets. Genetic discovery has been shown to be effective in the unbiased identification of novel drug targets and genome-wide association studies (GWASs) have begun to provide insight into genetic basis of osteoporosis. Over the last decade, GWASs have led to the identification of ~100 loci associated with BMD and other bone traits related to risk of fracture. However, there have been limited efforts to identify the causal genes underlying the GWAS loci or the mechanisms by which GWAS loci alter bone physiology. In this review, we summarize the current state of the field and discuss strategies for causal gene discovery and the evidence that the novel genes underlying GWAS loci are likely to be a new source of drug targets.

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Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials

Cited by 132 publications

References 41 publications

In Vitro Osteogenic Potential of Green Fluorescent Protein Labelled Human Embryonic Stem Cell‐Derived Osteoprogenitors

In Vitro Osteogenic Potential of Green Fluorescent Protein Labelled Human Embryonic Stem Cell‐Derived Osteoprogenitors

Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

Using GWAS to identify novel therapeutic targets for osteoporosis

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