Pluripotent stem cells as a source of osteoblasts for bone tissue regeneration

Zhu, Hui; Kimura, Takaharu; Swami, Srilatha; Wu, Joy Y.

doi:10.1016/j.biomaterials.2018.02.009

Cited by 37 publications

(35 citation statements)

References 61 publications

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“…Moreover, these assays do not correlate with in vivo bone formation, a more robust determination of osteoblast function . We have demonstrated that mouse embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) derived from Col2.3GFP transgenic mice, in which GFP expression marks osteoblasts, can be successfully differentiated to Col2.3GFP + osteoblast cells . We confirmed that Col2.3GFP + cells are enriched for osteoblast populations.…”

Section: Introductionmentioning

confidence: 89%

“…Genotyping was performed on tail genomic DNA to confirm the presence of the Col2.3GFP transgene. Tail tips were snipped, minced, trypsinized, and plated to derive fibroblast cells . Col2.3GFP fibroblasts were expanded for two passages and frozen for future use.…”

Section: Methodsmentioning

confidence: 99%

“…Calvarial osteoblasts were harvested by serial collagenase digestion as previously described, differentiated in osteogenic medium, and harvested after 3 weeks . Bone chips were harvested from Col2.3GFP transgenic mice and subjected to osteogenic differentiation as previously described …”

Section: Methodsmentioning

confidence: 99%

“…MSCs harvested from bone marrow stromal cells, as well as pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have been used as sources of osteoblasts and demonstrate osteogenic potential in vitro and/or in vivo . However, mesenchymal stromal cells gradually lose their multipotency and are limited by large donor variation, while ESCs and iPSCs are limited by low osteogenic differentiation efficiency and the risk of teratoma formation . Another approach, the direct conversion (or reprogramming) of adult somatic cells to an alternative cell lineage, has shown potential for clinical regeneration.…”

Section: Introductionmentioning

confidence: 99%

“…We confirmed that Col2.3GFP + cells are enriched for osteoblast populations. However, directed differentiation of pluripotent stem cells into osteoblasts is limited by low yields …”

Section: Introductionmentioning

confidence: 99%

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Direct Reprogramming of Mouse Fibroblasts into Functional Osteoblasts

Zhu

Swami

Yang

et al. 2019

Journal of Bone and Mineral Research

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Although induced pluripotent stem cells hold promise as a potential source of osteoblasts for skeletal regeneration, the induction of pluripotency followed by directed differentiation into osteoblasts is time consuming and low yield. In contrast, direct lineage reprogramming without an intervening stem/progenitor cell stage would be a more efficient approach to generate osteoblasts. We screened combinations of osteogenic transcription factors and identified four factors, Runx2, Osx, Dlx5, and ATF4, that rapidly and efficiently reprogram mouse fibroblasts derived from 2.3 kb type I collagen promoter‐driven green fluorescent protein (Col2.3GFP) transgenic mice into induced osteoblast cells (iOBs). iOBs exhibit osteoblast morphology, form mineralized nodules, and express Col2.3GFP and gene markers of osteoblast differentiation. The global transcriptome profiles validated that iOBs resemble primary osteoblasts. Genomewide DNA methylation analysis demonstrates that within differentially methylated loci, the methylation status of iOBs more closely resembles primary osteoblasts than mouse fibroblasts. We further demonstrate that Col2.3GFP+ iOBs have transcriptome profiles similar to GFP+ cells harvested from Col2.3GFP mouse bone chips. Functionally, Col2.3GFP+ iOBs form mineralized bone structures after subcutaneous implantation in immunodeficient mice and contribute to bone healing in a tibia bone fracture model. These findings provide an approach to derive and study osteoblasts for skeletal regeneration. © 2019 American Society for Bone and Mineral Research.

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Section: Introductionmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…We confirmed that Col2.3GFP + cells are enriched for osteoblast populations. However, directed differentiation of pluripotent stem cells into osteoblasts is limited by low yields …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Direct Reprogramming of Mouse Fibroblasts into Functional Osteoblasts

Zhu

Swami

Yang

et al. 2019

Journal of Bone and Mineral Research

Self Cite

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Bone, Stem Cells and Regeneration: Tissue Engineering Approaches

Grigoriadis

2021

Encyclopedia of Life Sciences

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The potential for regenerating bone and cartilage for cell‐based therapies has increased markedly in the past decades primarily due to advances in the understanding of molecular controls of embryonic skeletal development, in identification of refined stem cell/progenitor populations that are suitable for tissue regeneration, and in the discoveries of novel biomaterials that can mimic tissue architecture. In particular, modelling how the embryo makes the appropriate molecular decisions to fine tune the development of specific bone and cartilage subpopulations that form the complex skeleton has provided a platform upon which regenerative strategies can be translated to the clinic. It is, therefore, imperative to understand the basic biology of bone and skeletal tissues and apply lessons from developmental biology to identify the unique and appropriate cell populations that have potent regenerative potential when combined with optimal biomaterials. Key Concepts Bone/cartilage tissue engineering requires interaction between stem cells and biomaterials. Choosing the appropriate stem cell populations is extremely important and depends on the biological application studies. The use of directed differentiation of pluripotent stem cells that mimic developmental processes is an important advance in tissue engineering. Choosing the appropriate biomaterial with specific tunable properties is essential for supporting stem cell differentiation. Three‐dimensional approaches for tissue formation are important for translational studies. Defined preclinical models are necessary for screening stem cell/biomaterials constructs.

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Volumetric Printing of Thiol‐Ene Photo‐Cross‐Linkable Poly(ε‐caprolactone): A Tunable Material Platform Serving Biomedical Applications

et al. 2023

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Current thoroughly described biodegradable and cross‐linkable polymers mainly rely on acrylate cross‐linking. However, despite the swift cross‐linking kinetics of acrylates, the concomitant brittleness of the resulting materials limits their applicability. Here, photo‐cross‐linkable poly(ε‐caprolactone) networks through orthogonal thiol‐ene chemistry are introduced. The step‐growth polymerized networks are tunable, predictable by means of the rubber elasticity theory and it is shown that their mechanical properties are significantly improved over their acrylate cross‐linked counterparts. Tunability is introduced to the materials, by altering Mc (or the molar mass between cross‐links), and its effect on the thermal properties, mechanical strength and degradability of the materials is evaluated. Moreover, excellent volumetric printability is illustrated and the smallest features obtained via volumetric 3D‐printing to date are reported, for thiol‐ene systems. Finally, by means of in vitro and in vivo characterization of 3D‐printed constructs, it is illustrated that the volumetrically 3D‐printed materials are biocompatible. This combination of mechanical stability, tunability, biocompatibility, and rapid fabrication by volumetric 3D‐printing charts a new path toward bedside manufacturing of biodegradable patient‐specific implants.

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Pluripotent stem cells as a source of osteoblasts for bone tissue regeneration

Cited by 37 publications

References 61 publications

Direct Reprogramming of Mouse Fibroblasts into Functional Osteoblasts

Direct Reprogramming of Mouse Fibroblasts into Functional Osteoblasts

Bone, Stem Cells and Regeneration: Tissue Engineering Approaches

Volumetric Printing of Thiol‐Ene Photo‐Cross‐Linkable Poly(ε‐caprolactone): A Tunable Material Platform Serving Biomedical Applications

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