Materials as stem cell regulators

Murphy, William L.; McDevitt, Todd C.; Engler, Adam J.

doi:10.1038/nmat3937

Cited by 824 publications

(733 citation statements)

References 121 publications

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“…Moreover, the biomaterials may stimulate angiogenesis and promote differentiation of stem cells 12. Behaviours of the transplanted stem cells may be induced or manipulated by inherent material properties (such as adhesiveness, stiffness, nanostructure or degradability) 13. However, intramyocardial injection of stem cells and hydrogel matrix almost has no effect on restricting ventricular dilation.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium

Wang

et al. 2017

J Cellular Molecular Medi

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Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF‐1α, Tβ4, VEGF and SDF‐1 expression and decreased CXCL14 expression in hypoxic and serum‐deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF‐1α, Tβ4, VEGF, SDF‐1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial‐derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c‐kit+ cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c‐kit+ cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium

Wang

et al. 2017

J Cellular Molecular Medi

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“…[7,8] For example, by mimicking important features of a target tissue including the extracellular microenvironment, 3D-biomaterials have the potential to instruct cell fate and function in ways not previously attainable. [9] Therefore, although still exploratory, we envisage the synergism of stem-cell biology and 3D-biomaterial technology being influential in iPSC-based research and translation.…”

mentioning

confidence: 99%

3D Bioprinting Human Induced Pluripotent Stem Cell Constructs for In Situ Cell Proliferation and Successive Multilineage Differentiation

Tomaskovic-Crook

Wallace

et al. 2017

Adv Healthcare Materials

188

164

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The ability to create 3D tissues from induced pluripotent stem cells (iPSCs) is poised to revolutionize stem cell research and regenerative medicine, including individualized, patient‐specific stem cell‐based treatments. There are, however, few examples of tissue engineering using iPSCs. Their culture and differentiation is predominantly planar for monolayer cell support or induction of self‐organizing embryoids (EBs) and organoids. Bioprinting iPSCs with advanced biomaterials promises to augment efforts to develop 3D tissues, ideally comprising direct‐write printing of cells for encapsulation, proliferation, and differentiation. Here, such a method, employing a clinically amenable polysaccharide‐based bioink, is described as the first example of bioprinting human iPSCs for in situ expansion and sequential differentiation. Specifically, we have extrusion printed the bioink including iPSCs, alginate (Al; 5% weight/volume [w/v]), carboxymethyl‐chitosan (5% w/v), and agarose (Ag; 1.5% w/v), crosslinked the bioink in calcium chloride for a stable and porous construct, proliferated the iPSCs within the construct and differentiated the same iPSCs into either EBs comprising cells of three germ lineages—endoderm, ectoderm, and mesoderm, or more homogeneous neural tissues containing functional migrating neurons and neuroglia. This defined, scalable, and versatile platform is envisaged being useful in iPSC research and translation for pharmaceuticals development and regenerative medicine.

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“…Studies in murine ES cells (3,4) and tissue-specific stem cells (5)(6)(7)(8)(9)(10) indicate that the adhesive and mechanical properties of the substratum used can influence cell fate decisions (11). For example, human mesenchymal stem (hMS) cells are sensitive to changes in substrate elasticity and respond by differentiating toward distinct cell lineages depending on the stiffness of the matrix (5).…”

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confidence: 99%

Substratum-induced differentiation of human pluripotent stem cells reveals the coactivator YAP is a potent regulator of neuronal specification

Musah¹,

Wrighton

Zaltsman

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Physical stimuli can act in either a synergistic or antagonistic manner to regulate cell fate decisions, but it is less clear whether insoluble signals alone can direct human pluripotent stem (hPS) cell differentiation into specialized cell types. We previously reported that stiff materials promote nuclear localization of the Yes-associated protein (YAP) transcriptional coactivator and support long-term self-renewal of hPS cells. Here, we show that even in the presence of soluble pluripotency factors, compliant substrata inhibit the nuclear localization of YAP and promote highly efficient differentiation of hPS cells into postmitotic neurons. In the absence of neurogenic factors, the effective substrata produce neurons rapidly (2 wk) and more efficiently (>75%) than conventional differentiation methods. The neurons derived from substrate induction express mature markers and possess action potentials. The hPS differentiation observed on compliant surfaces could be recapitulated on stiff surfaces by adding small-molecule inhibitors of F-actin polymerization or by depleting YAP. These studies reveal that the matrix alone can mediate differentiation of hPS cells into a mature cell type, independent of soluble inductive factors. That mechanical cues can override soluble signals suggests that their contributions to early tissue development and lineage commitment are profound.H uman pluripotent stem (hPS) cells, which include human embryonic (hES) and human induced pluripotent stem cells, possess the remarkable capacity to self-renew indefinitely and differentiate into almost any specialized cell type (1, 2). They represent a potentially unlimited supply of cells for regenerative medicine, drug screening, and studies of human development. These applications require efficient and reproducible conditions to direct hPS cell differentiation into specialized cell types, including neuronal cells. To date, the focus has been on identifying soluble factors, such as growth factors and small molecules, that can influence hPS cell differentiation. The ability of insoluble signals to promote hPS cell-lineage specification remains less clear.Studies in murine ES cells (3, 4) and tissue-specific stem cells (5-10) indicate that the adhesive and mechanical properties of the substratum used can influence cell fate decisions (11). For example, human mesenchymal stem (hMS) cells are sensitive to changes in substrate elasticity and respond by differentiating toward distinct cell lineages depending on the stiffness of the matrix (5). These hMS cells, however, tend to exist in heterogeneous cell populations and lack a specific and unique cell characterization marker (12). Their differentiation capacity is restricted to a few tissues that arise from the mesoderm lineage, such as bone, fat, and cartilage. Indeed, there are questions about whether these cells undergo transdifferentiation to cell types, such as neurons (12)(13)(14). With the unique ability to differentiate into almost any cell type, hPS cells serve as an excellent model for und...

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Materials as stem cell regulators

Cited by 824 publications

References 121 publications

Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium

Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium

3D Bioprinting Human Induced Pluripotent Stem Cell Constructs for In Situ Cell Proliferation and Successive Multilineage Differentiation

Substratum-induced differentiation of human pluripotent stem cells reveals the coactivator YAP is a potent regulator of neuronal specification

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