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Project description:Engineering functional tissues for transplantation requires insight into epigenetic mechanisms that regulate stem cell fate. We have developed the Wnt-induced osteogenic tissue model (WIOTM), a platform that recapitulates human osteogenesis, and identified acetylation of histone H3 at lysine 14 (H3K14ac) as a critical epigenetic regulator in human skeletal stem cells (hSSCs). In WIOTM, localized Wnt signals drive asymmetric cell division (ACD), yielding a proximal hSSC with high H3K14ac and a distal daughter with reduced H3K14ac that migrates into the 3D collagen matrix and initiate osteogenic differentiation. Disrupting H3K14ac in hSSCs abrogates ACD and WIOTM formation. To test whether hSSCs maintain H3K14ac in vivo, we formed the WIOTM on Wnt-functionalized polymer bandages and transplanted them into calvarial defects. The WIOTM contributed to bone repair, and human cells adjacent to the bandages retained high H3K14ac despite the injury environment. These findings establish WIOTM as both a mechanistic and translational platform for regenerative medicine.
2026-03-09 | GSE310736 | GEO
Project description:Engineering functional tissues for transplantation requires insight into epigenetic mechanisms that regulate stem cell fate. We have developed the Wnt-induced osteogenic tissue model (WIOTM), a platform that recapitulates human osteogenesis, and identified acetylation of histone H3 at lysine 14 (H3K14ac) as a critical epigenetic regulator in human skeletal stem cells (hSSCs). In WIOTM, localized Wnt signals drive asymmetric cell division (ACD), yielding a proximal hSSC with high H3K14ac and a distal daughter with reduced H3K14ac that migrates into the 3D collagen matrix and initiate osteogenic differentiation. Disrupting H3K14ac in hSSCs abrogates ACD and WIOTM formation. To test whether hSSCs maintain H3K14ac in vivo, we formed the WIOTM on Wnt-functionalized polymer bandages and transplanted them into calvarial defects. The WIOTM contributed to bone repair, and human cells adjacent to the bandages retained high H3K14ac despite the injury environment. These findings establish WIOTM as both a mechanistic and translational platform for regenerative medicine.
2026-03-09 | GSE310734 | GEO
Project description:Engineering functional tissues for transplantation requires insight into epigenetic mechanisms that regulate stem cell fate. We have developed the Wnt-induced osteogenic tissue model (WIOTM), a platform that recapitulates human osteogenesis, and identified acetylation of histone H3 at lysine 14 (H3K14ac) as a critical epigenetic regulator in human skeletal stem cells (hSSCs). In WIOTM, localized Wnt signals drive asymmetric cell division (ACD), yielding a proximal hSSC with high H3K14ac and a distal daughter with reduced H3K14ac that migrates into the 3D collagen matrix and initiate osteogenic differentiation. Disrupting H3K14ac in hSSCs abrogates ACD and WIOTM formation. To test whether hSSCs maintain H3K14ac in vivo, we formed the WIOTM on Wnt-functionalized polymer bandages and transplanted them into calvarial defects. The WIOTM contributed to bone repair, and human cells adjacent to the bandages retained high H3K14ac despite the injury environment. These findings establish WIOTM as both a mechanistic and translational platform for regenerative medicine.
2026-03-09 | GSE310733 | GEO
Project description:Wnt-materials sustain H3K14-acetylation in human skeletal stem cells for tissue engineering and bone repair
| PRJNA1367000 | ENA
Project description:This review discusses and summarizes the recent developments and advances in the use of biodegradable materials for bone repair purposes. The choice between using degradable and non-degradable devices for orthopedic and maxillofacial applications must be carefully weighed. Traditional biodegradable devices for osteosynthesis have been successful in low or mild load bearing applications. However, continuing research and recent developments in the field of material science has resulted in development of biomaterials with improved strength and mechanical properties. For this purpose, biodegradable materials, including polymers, ceramics and magnesium alloys have attracted much attention for osteologic repair and applications. The next generation of biodegradable materials would benefit from recent knowledge gained regarding cell material interactions, with better control of interfacing between the material and the surrounding bone tissue. The next generations of biodegradable materials for bone repair and regeneration applications require better control of interfacing between the material and the surrounding bone tissue. Also, the mechanical properties and degradation/resorption profiles of these materials require further improvement to broaden their use and achieve better clinical results.
| S-EPMC5512653 | biostudies-other
Project description:Although skeletal muscle is highly regenerative following injury or disease, endogenous self-regeneration is severely impaired in conditions of volume traumatic muscle loss. Consequently, tissue engineering approaches are a promising means to regenerate skeletal muscle. Biological scaffolds serve as not only structural support for the promotion of cellular ingrowth but also impart potent modulatory signaling cues that may be beneficial for tissue regeneration. In this work, the progress of tissue engineering approaches for skeletal muscle engineering and regeneration is overviewed, with a focus on the techniques to create biomimetic engineered tissue using extracellular cues. These factors include mechanical and electrical stimulation, geometric patterning, and delivery of growth factors or other bioactive molecules. The progress of evaluating the therapeutic efficacy of these approaches in preclinical models of muscle injury is further discussed.
| S-EPMC6589032 | biostudies-literature
Project description:Bone morphogenetic proteins (BMPs) participate in multiple stages of the fetal skeletogenic program from promoting cell condensation to regulating chondrogenesis and bone formation through endochondral ossification. Here, we show that these pleiotropic functions are recapitulated when recombinant BMPs are used to augment skeletal tissue repair. In addition to their well-documented ability to stimulate chondrogenesis in a skeletal injury, we show that recombinant BMPs (rBMPs) simultaneously suppress the differentiation of skeletal progenitor cells in the endosteum and bone marrow cavity to an osteoblast lineage. Both the prochondrogenic and antiosteogenic effects are achieved because rBMP inhibits endogenous beta-catenin-dependent Wnt signaling. In the injured periosteum, this repression of Wnt activity results in sox9 upregulation; consequently, cells in the injured periosteum adopt a chondrogenic fate. In the injured endosteum, rBMP also inhibits Wnt signaling, which results in the runx2 and collagen type I downregulation; consequently, cells in this region fail to differentiate into osteoblasts. In muscle surrounding the skeletal injury site, rBMP treatment induces Smad phosphorylation followed by exuberant cell proliferation, an increase in alkaline phosphatase activity, and chondrogenic differentiation. Thus different populations of adult skeletal progenitor cells interpret the same rBMP stimulus in unique ways, and these responses mirror the pleiotropic effects of BMPs during fetal skeletogenesis. These mechanistic insights may be particularly useful for optimizing the reparative potential of rBMPs while simultaneously minimizing their adverse outcomes.
| S-EPMC3153130 | biostudies-literature
Project description:Materials based on biodegradable polyesters, such as poly(butylene terephthalate) (PBT) or poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT), have potential application as pro-regenerative scaffolds for bone tissue engineering. Herein, the preparation of films composed of PBT or PBTAT and an engineered spider silk protein, (eADF4(C16)), that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported. Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering.
| S-EPMC5456849 | biostudies-literature
Project description:There has been an escalation in reports over the last decade examining the efficacy of bone marrow derived mesenchymal stem/stromal cells (BMSC) in bone tissue engineering and regenerative medicine-based applications. The multipotent differentiation potential, myelosupportive capacity, anti-inflammatory and immune-modulatory properties of BMSC underpins their versatile nature as therapeutic agents. This review addresses the current limitations and challenges of exogenous autologous and allogeneic BMSC based regenerative skeletal therapies in combination with bioactive molecules, cellular derivatives, genetic manipulation, biocompatible hydrogels, solid and composite scaffolds. The review highlights the current approaches and recent developments in utilizing endogenous BMSC activation or exogenous BMSC for the repair of long bone and vertebrae fractures due to osteoporosis or trauma. Current advances employing BMSC based therapies for bone regeneration of craniofacial defects is also discussed. Moreover, this review discusses the latest developments utilizing BMSC therapies in the preclinical and clinical settings, including the treatment of bone related diseases such as Osteogenesis Imperfecta.
| S-EPMC7767389 | biostudies-literature
Project description:During DNA replication, thousands of replication origins are activated across the genome. Chromatin architecture contributes to origin specification and usage, yet it remains unclear which chromatin features impact on DNA replication. Here, we perform a RNAi screen for chromatin regulators implicated in replication control by measuring RPA accumulation upon replication stress. We identify six factors required for normal rates of DNA replication and characterize a function of the bromodomain and PHD finger-containing protein 3 (BRPF3) in replication initiation. BRPF3 forms a complex with HBO1 that specifically acetylates histone H3K14, and genomewide analysis shows high enrichment of BRPF3, HBO1 and H3K14ac at ORC1-binding sites and replication origins found in the vicinity of TSSs. Consistent with this, BRPF3 is necessary for H3K14ac at selected origins and efficient origin activation. CDC45 recruitment, but not MCM2-7 loading, is impaired in BRPF3-depleted cells, identifying a BRPF3-dependent function of HBO1 in origin activation that is complementary to its role in licencing. We thus propose that BRPF3-HBO1 acetylation of histone H3K14 around TSS facilitates efficient activation of nearby replication origins.
| S-EPMC4718456 | biostudies-literature