Strategies for Oral Mucosal Repair by Engineering 3D Tissues with Pluripotent Stem Cells

Hewitt, Kyle J.; Shamis, Yulia; Gerami‐Naini, Behzad; Garlick, Jonathan A.

doi:10.1089/wound.2013.0480

Cited by 4 publications

(3 citation statements)

References 48 publications

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“…Three-dimensional (3D) culturing has become a novel strategy to generate tissues like oral mucosa, osteoclasts, and cardiomyocytes for regenerative therapy 21 – 23 . Compared to single-layer 2D culturing, 3D structures allow cells to freely distribute in a manner similar to the natural microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Promoting Induced Pluripotent Stem Cell-driven Biomineralization and Periodontal Regeneration in Rats with Maxillary-Molar Defects using Injectable BMP-6 Hydrogel

Chien

Chang

Wang

et al. 2018

Sci Rep

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Periodontal disease may cause considerable destruction of alveolar bone, periodontal ligaments (PDLs) and cementum and even lead to progressive oral dysfunction. Periodontal tissue regeneration is the ultimate goal of periodontal disease treatment to reconstruct both structures and functions. However, the regenerative efficiency is low, possibly due to the lack of a proper periodontal microenvironment. In this study, we applied an injectable and thermosensitive chitosan/gelatin/glycerol phosphate hydrogel to provide a 3D environment for transplanted stem cells and to enhance stem cell delivery and engraftment. The iPSCs-BMP-6-hydrogel complex promoted osteogenesis and the differentiation of new connective tissue and PDL formation. In animal models of maxillary-molar defects, the iPSCs-BMP-6-hydrogel-treated group showed significant mineralization with increased bone volume, trabecular number and trabecular thickness. Synergistic effects of iPSCs and BMP-6 increased both bone and cementum formation. IPSCs-BMP-6-hydrogel-treated animals showed new bone synthesis (increased ALP- and TRAP-positive cells), new PDL regeneration (shown through Masson’s trichrome staining and a qualification assay), and reduced levels of inflammatory cytokines. These findings suggest that hydrogel-encapsulated iPSCs combined with BMP-6 provide a new strategy to enhance periodontal regeneration. This combination not only promoted stem cell-derived graft engraftment but also minimized the progress of inflammation, which resulted in highly possible periodontal regeneration.

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Section: Discussionmentioning

confidence: 99%

Promoting Induced Pluripotent Stem Cell-driven Biomineralization and Periodontal Regeneration in Rats with Maxillary-Molar Defects using Injectable BMP-6 Hydrogel

Chien

Chang

Wang

et al. 2018

Sci Rep

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“…iPS technology reprograms somatic cells into a pluripotent state, and avoids ethical concerns associated with embryonic cells (15,16). Fibroblasts derived from iPS cells ('post-iPSF') were generated following reprogramming of a foreskin fibroblast source cell (pre-iPSF), and produced an augmented ECM enriched in GAG, fibronectin, Collagen type III (which is found in elevated levels in foetal ECM; this is notable as foetal wounds heal scar free), and enriched in vascular endothelial growth factor (VEGF) enhancing invitro vascularization (17)(18)(19)(20)(21)(22)(23)(24)(25)(26). In order to fully exploit the potential of rejuvenated ECM for scaffold fabrication, we refined ascorbic acid concentration (27) and cell seeding density (28,29) to enhance the quantity of post-iPSF ECM, while maintaining the same ECM constituents (13).…”

Section: Introductionmentioning

confidence: 99%

The Development of Tissue Engineering Scaffolds Using Matrix from iPS-Reprogrammed Fibroblasts

Santarella

O’Brien

Garlick

et al. 2021

Methods in Molecular Biology

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Tissue engineering solutions have been widely explored for enhanced healing of skin wounds. Diabetic foot ulcers (DFU) are particularly challenging wounds to heal for a variety of reasons, including aberrant ECM, dysregulation of vascularization, and persistent inflammation. Tissue engineering approaches, such as porous collagen-based scaffolds, have shown promise in replacing the current treatments of surgical debridement and topical treatments. Collagen-glycosaminoglycan scaffolds, which are FDA approved for diabetic foot ulcers, can benefit from further functionalization by incorporation of additional signalling factors or extracellular matrix molecules. One option for this is to incorporate matrix from a rejuvenated cell source, as wounds in younger patients heal more quickly. Induced pluripotent stem cells (iPS) are generated from somatic cells and share many functional similarities with embryonic stem cells (ES), while avoiding the ethical concerns. Fibroblasts differentiated from iPS cells have been shown to enrich their ECM with glycosaminoglycan (GAGs), collagen type III and fibronectin, to have an increased ECM production, and to be pro-angiogenic. Here we describe a technique to grow matrix from post-iPS fibroblasts, and to develop a scaffold from this matrix, in combination with collagen, with the goal of enhancing wound healing. By activating scaffolds with extracellular matrix (ECM) from fibroblasts derived from an iPS source (post-iPSF), the scaffolds are enriched with beneficial elements like GAGs, collagen type III, fibronectin, and VEGF. We believe these scaffolds can enhance skin regeneration and that the techniques can be modified for other tissue engineering applications.

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“…Cell studies were performed with HepG2 (cluster type) and SK-HEP-1 (monolayer type) cell lines as a co-culture model for carrying cells to the target site within the suture coating and on the surface respectively. Potential applications for such NFCA hydrogels are: cell-carrier systems including oral mucosa repair [ 33 , 34 ], ulcer treatment [ 35 , 36 ], and for example Crohn’s disease, which has been recently investigated in treatment of fistulas with adipose-derived stem cells [ 37 – 39 ], where cell transplantations were done with separate injections at the sutured internal openings of the fistulas. Additionally, cell co-culture systems enable different cell types to be utilized in a single treatment system [ 40 ], or a model that can be utilized in studies evaluating treatment efficiencies [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

Nanofibrillar cellulose-alginate hydrogel coated surgical sutures as cell-carrier systems

et al. 2017

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Hydrogel nanomaterials, especially those that are of non-human and non-animal origins, have great potential in biomedical and pharmaceutical sciences due to their versatility and inherent soft-tissue like properties. With the ability to simulate native tissue function, hydrogels are potentially well suited for cellular therapy applications. In this study, we have fabricated nanofibrillar cellulose-alginate (NFCA) suture coatings as biomedical devices to help overcome some of the limitations related to cellular therapy, such as low cell survivability and distribution out of target tissue. The addition of sodium alginate 8% (w/v) increased the NFCA hydrogel viscosity, storage and loss moduli by slightly under one order of magnitude, thus contributing significantly to coating strength. Confocal microscopy showed nearly 100% cell viability throughout the 2-week incubation period within and on the surface of the coating. Additionally, typical morphologies in the dual cell culture of spheroid forming HepG2 and monolayer type SK-HEP-1 were observed. Twelve out of 14 NFCA coated surgical sutures remained intact during the suturing operation with various mice and rat tissue; however, partial peeling off was observed in 2 of the coated sutures. We conclude that NFCA suture coatings could perform as cell-carrier systems for cellular based therapy and post-surgical treatment.

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Strategies for Oral Mucosal Repair by Engineering 3D Tissues with Pluripotent Stem Cells

Cited by 4 publications

References 48 publications

Promoting Induced Pluripotent Stem Cell-driven Biomineralization and Periodontal Regeneration in Rats with Maxillary-Molar Defects using Injectable BMP-6 Hydrogel

Promoting Induced Pluripotent Stem Cell-driven Biomineralization and Periodontal Regeneration in Rats with Maxillary-Molar Defects using Injectable BMP-6 Hydrogel

The Development of Tissue Engineering Scaffolds Using Matrix from iPS-Reprogrammed Fibroblasts

Nanofibrillar cellulose-alginate hydrogel coated surgical sutures as cell-carrier systems

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