Three-dimensional polymer scaffolds for enhanced differentiation of human mesenchymal stem cells to hepatocyte-like cells: a comparative study

Chitrangi, Swati; Nair, Prabha D.; Khanna, Aparna

doi:10.1002/term.2136

Cited by 25 publications

(23 citation statements)

References 32 publications

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“…9,31,41,46,51 Our finding that 3D biomaterials are potent modulators of endothelial specification concurs with Zhang et al that demonstrated a significant improvement of endothelial differentiation 3D fibrin (45% efficiency), compared to 2D (10% efficiency) substrates. 58 We believe this is the first report of endothelial differentiation of iPSCs within 3D synthetic polymer scaffolds.…”

Section: Discussionsupporting

confidence: 90%

Microfibrous Scaffolds Enhance Endothelial Differentiation and Organization of Induced Pluripotent Stem Cells

et al. 2017

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INTRODUCTION Human induced pluripotent stem cells (iPSCs) are a promising source of endothelial cells (iPSC-ECs) for engineering three-dimensional (3D) vascularized cardiac tissues. To mimic cardiac microvasculature, in which capillaries are oriented in parallel, we hypothesized that endothelial differentiation of iPSCs within topographically aligned 3D scaffolds would be a facile one-step approach to generate iPSC-ECs as well as induce aligned vascular organization. METHODS Human iPSCs underwent endothelial differentiation within electrospun 3D polycaprolactone (PCL) scaffolds having either randomly oriented or parallel-aligned microfibers. Using transcriptional, protein, and endothelial functional assays, endothelial differentiation was compared between conventional two-dimensional (2D) films and 3D scaffolds having either randomly oriented or aligned microfibers. Furthermore, the role of parallel-aligned microfiber patterning on the organization of vessel-like networks was assessed. RESULTS The cells in both the randomly oriented and aligned 3D scaffolds demonstrated an 11-fold upregulation in gene expression of the endothelial phenotypic marker, CD31, compared to cells on 2D films. This upregulation corresponded to >3-fold increase in CD31 protein expression in 3D scaffolds, compared to 2D films. Concomitantly, other endothelial phenotypic markers including CD144 and endothelial nitric oxide synthase also showed significant transcriptional upregulation in 3D scaffolds by >7-fold, compared to 2D films. Nitric oxide production, which is characteristic of endothelial function, was produced 4-fold more abundantly in 3D scaffolds, compared to on 2D PCL films. Within aligned scaffolds, the iPSC-ECs displayed parallel-aligned vascular-like networks with 70% longer branch length, compared to cells in randomly oriented scaffolds, suggesting that fiber topography modulates vascular network-like formation and patterning. CONCLUSION Together, these results demonstrate that 3D scaffold structure promotes endothelial differentiation, compared to 2D substrates, and that aligned topographical patterning induces anisotropic vascular network organization.

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Section: Discussionsupporting

confidence: 90%

Microfibrous Scaffolds Enhance Endothelial Differentiation and Organization of Induced Pluripotent Stem Cells

et al. 2017

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“…For instance, several gelatin-based scaffolds have been tailored to support hepatic tissues. [179][180][181] In an interesting study, a chitosan/gelatin composite scaffold with an organized microstructure analogous to the physiological hepatic tissue was shown to support the growth and proper development of hepatocytes in vitro. 182 This indicates that mimicking the topography of the native tissue is essential to generate scaffolds for tissue replacement.…”

Section: Gelatin-cell Composites For Cartilage and Bone Tissue Regenementioning

confidence: 99%

Engineering and Functionalization of Gelatin Biomaterials: From Cell Culture to Medical Applications

Bello

Kim

et al. 2020

Tissue Engineering Part B: Reviews

399

259

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Health care and medicine were revolutionized in recent years by the development of biomaterials, such as stents, implants, personalized drug delivery systems, engineered grafts, cell sheets, and other transplantable materials. These materials not only support the growth of cells before transplantation but also serve as replacements for damaged tissues in vivo. Among the various biomaterials available, those made from natural biological sources such as extracellular proteins (collagen, fibronectin, laminin) have shown significant benefits, and thus are widely used. However, routine biomaterial-based research requires copious quantities of proteins and the use of pure and intact extracellular proteins could be highly cost ineffective. Gelatin is a molecular derivative of collagen obtained through the irreversible denaturation of collagen proteins. Gelatin shares a very close molecular structure and function with collagen and thus is often used in cell and tissue culture to replace collagen for biomaterial purposes. Recent technological advancements such as additive manufacturing, rapid prototyping, and three-dimensional printing, in general, have resulted in great strides toward the generation of functional gelatin-based materials for medical purposes. In this review, the structural and molecular similarities of gelatin to other extracellular matrix proteins are compared and analyzed. Current strategies for gelatin crosslinking and production are described and recent applications of gelatin-based biomaterials in cell culture and tissue regeneration are discussed. Finally, recent improvements in gelatin-based biomaterials for medical applications and future directions are elaborated.

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“…10 It is also used to replace defective body cells 82 and improve local tissue defects. 83 Cell therapies initially involved autologous bone marrow cell infusion, but methods for use of specific cells such as mesenchymal stem cells and macrophages have been developed.…”

Section: Use Of Tissue Specific Stem Cellsmentioning

confidence: 99%

Role of Biological Scaffolds, Hydro Gels and Stem Cells in Tissue Regeneration Therapy

Upadhyay¹

2017

ATROA

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Present review article emphasizes role of biological scaffolds, hydrogels and stem cells in tissue engineering mainly in regeneration or repairing of damaged tissues. Highly porous scaffold biomaterials are developed which act as templates for tissue regeneration and potentially guide the growth of new tissue. Present article also describes de-cellularization, cell printing, vascularization, integration of cross linking of methods for scaffolding of biomaterials to reproduce and recapitulate complexity in engineered tissues. It also explains different scaffold types, polymer hydrogels which are necessary for formation of microstructure, cell attachment, differentiation, tissue vascularization and integration. It also explains use of induced pluripotent stem cells (iPSCs) and engineered MSCs as new diagnostic and potential therapeutic tools to remove sustained damage and complications from organ failures. These engineered MSCs assist in making self-assembling supramolecular hydrogels, which have larger applications in cell therapy of intractable diseases and tissue regeneration. No doubt development of more advanced biomaterials, growth factors and stem cell derived products/factors and tissue transplantation methods based on cell regeneration programming will revolutionize the clinical therapeutics. This article suggests identification of new biomaterials/biomolecules such as growth factors, scaffolds, integration, adhesion and regulatory molecules and cell secreted factors which can induce major metabolic and signaling pathways during phase of tissue repairing and induction of regeneration. This innovative research area needs many conceptual improvements in organ therapies, methods and technological advancement to scale more services to the human society.

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Three-dimensional polymer scaffolds for enhanced differentiation of human mesenchymal stem cells to hepatocyte-like cells: a comparative study

Cited by 25 publications

References 32 publications

Microfibrous Scaffolds Enhance Endothelial Differentiation and Organization of Induced Pluripotent Stem Cells

Microfibrous Scaffolds Enhance Endothelial Differentiation and Organization of Induced Pluripotent Stem Cells

Engineering and Functionalization of Gelatin Biomaterials: From Cell Culture to Medical Applications

Role of Biological Scaffolds, Hydro Gels and Stem Cells in Tissue Regeneration Therapy

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