The effects of electrospun substrate-mediated cell colony morphology on the self-renewal of human induced pluripotent stem cells

Maldonado, Maricela; Wong, Lauren Y.; Echeverría, Cristina; Ico, Gerardo; Low, Karen; Fujimoto, Taylor; Johnson, Jed; Nam, Jin

doi:10.1016/j.biomaterials.2015.01.037

Cited by 51 publications

(60 citation statements)

References 53 publications

(33 reference statements)

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“…As shown in Figure A, both 130‐ and 330‐μm thick versions of the PU matrix showed robust attachment of CK positive cells after 8 days incubation. Although studies have been published indicating that the lack of a hydrophobic surface inhibits cell adhesion to uncoated PU matrices, the findings are in accordance with studies showing robust attachment of MSCs as well as iPSCs to Nanofiber Solutions scaffold in the absence of a protein coating (Gustafsson et al ., ; Maldonado et al ., ). To investigate growth of these cells on the matrix, parallel samples were incubated for 14 days and embedded for sectioning.…”

Section: Resultsmentioning

confidence: 96%

Full-thickness oesophageal regeneration in pig using a polyurethane mucosal cell seeded graft

Barron

Blanco

Aho

et al. 2017

J Tissue Eng Regen Med

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Malignant oesophageal pathology typically requires resection of a portion of oesophagus. The aim of this study was to investigate attachment and growth of swine oesophageal mucosal cells on electrospun synthetic nanofibre matrices of varying chemistries and to determine whether a mucosal-seeded graft, in a swine animal model, could induce regeneration. Swine mucosal oesophageal cells were isolated and seeded them onto five different matrix materials. Matrix samples were cultured for up to 14 days, after which matrices were analysed for cell attachment. Attachment varied for each of the matrix materials tested, with the most rigid showing the lowest levels of attachment. Importantly, sections of these matrices illustrated that multiple layers of mucosal cells formed, mimicking endogenous oesophageal structure. A tdTomato reporter line (mucosal tdt cells) was created to enable cell tracking. As polyurethane matrix was found optimal through in vitro testing, a graft was prepared using mucosal tdt cells, along with an unseeded control, and implanted into swine for determination of oesophageal regeneration. Mucosal seeded polyurethane grafts initiated full thickness regeneration of the oesophagus, including epithelial, submucosal, and skeletal muscle layers which were highly vascularized. Interestingly, an unseeded graft showed similar regeneration, indicating that the role of cells in the process of oesophageal regeneration is still unclear. The electrospun polyurethane matrix does appear suitable for multilayered cellular attachment and growth of oesophageal mucosal cells, and implantation of polyurethane grafts initiated full thickness regeneration of the oesophagus, indicating potential for oesophageal reconstruction in humans.

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Section: Resultsmentioning

confidence: 96%

Full-thickness oesophageal regeneration in pig using a polyurethane mucosal cell seeded graft

Barron

Blanco

Aho

et al. 2017

J Tissue Eng Regen Med

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“…Our approach is based on plug-and-play recordings without cell reseeding, which should greatly simplify the routine applications. More systematic studies will also be required for optimization of mechanic stiffness and mesh size of nanofibers for both hiPSC cultivation and lineage specific differentiation 46 . The patch form of differentiated cells could be robust, versatile, and easy to use for different cell-based assays.…”

Section: Discussionmentioning

confidence: 99%

Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers

Tang

Liu

et al. 2016

Nanoscale

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Extensive efforts have been devoted to develop new substrates for culture and differentiation of human induced pluripotent stem cells (hiPSCs) toward cardiac cell-based assays. A more exciting prospect is the construction of cardiac tissue for robust drug screening and cardiac tissue repairing. Here, we developed a patch method by electrospinning and crosslinking of monolayer gelatin nanofibers on a honeycomb frame made of poly(ethylene glycol) diacrylate (PEGDA). The monolayer of the nanofibrous structure can support cells with minimal exogenous contact and a maximal efficiency of cell-medium exchange whereas a single hiPSC colony can be uniformly formed in each of the honeycomb compartments. By modulating the treatment time of the ROCK inhibitor Y-27632, the shape of the hiPSC colony could be controlled from a flat layer to a hemisphere. Afterwards, the induction and differentiation of hiPSCs were achieved on the same patch, leading to a uniform cardiac layer with homogeneous contraction. This cardiac layer could then be used for extracellular recording with a commercial multi-electrode array, showing representative field potential waveforms of matured cardiac tissues with appropriate drug responses.

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“…93 Similarly, the stiffness of electrospun substrates controlled iPSC proliferation. 94 In adult and neonatal cardiomyocytes, compliant elastic matrices enhanced clonal expansion by suppressing maturation and promoting de-differentiation, modifying the sarcomere network, and promoting cell division. 95 …”

Section: Stem Cells Respond To Forcesmentioning

confidence: 99%

Mechanical forces direct stem cell behaviour in development and regeneration

Vining

Mooney

2017

Nat Rev Mol Cell Biol

1,172

958

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Stem cells and their local microenvironment, or niche, communicate through mechanical, cues to regulate cell fate and cell behaviour, and to guide developmental processes. During embryonic development, mechanical forces are involved in patterning and organogenesis. The physical environment of pluripotent stem cells regulates their differentiation and self-renewal. Mechanical and physical cues are also important in adult tissues, where adult stem cells require physical interactions with the extracellular matrix to maintain their potency. In vitro, synthetic models of the stem cell niche can be used to precisely control and manipulate the biophysical and biochemical properties of the stem cell microenvironment and examine how the mode and magnitude of mechanical cues, such as matrix stiffness or applied forces, direct stem cell differentiation and function. Fundamental insights on the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.

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The effects of electrospun substrate-mediated cell colony morphology on the self-renewal of human induced pluripotent stem cells

Cited by 51 publications

References 53 publications

Full-thickness oesophageal regeneration in pig using a polyurethane mucosal cell seeded graft

Full-thickness oesophageal regeneration in pig using a polyurethane mucosal cell seeded graft

Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers

Mechanical forces direct stem cell behaviour in development and regeneration

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