The effect of endothelial cells on hESC-derived pancreatic progenitors in a 3D environment

Weizman, Abraham; Michael, Inbal; Wiesel-Motiuk, Naama; Rezania, Alireza; Levenberg, Shulamit

doi:10.1039/c4bm00304g

Cited by 16 publications

(12 citation statements)

References 26 publications

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“…31,53,93,102,106,195–197 Furthermore, it was shown that successful differentiation into early ISC is possible in vitro; maturation, however, requires in vivo conditions. 31,101,196–200 There has been extensive research on the differentiation of insulin-secreting beta cells from human pluri- and multipotent stem cells (n = 47 studies), such as hiPSC, 53,106,107,201,202 hESC, 93,195,197–199,203–206 and MSC. 31,100–102,207–210 Again, these approaches are based on mimicking the processes of natural pancreas embryology by stepwise reproduction with the addition of growth factors and other molecules.…”

Section: Resultsmentioning

confidence: 99%

“…Scaffold size, mechanical stability, and diffusion distances affect the choice further. Among the in vivo studies included (n = 91) the ISC/scaffold construct was transplanted into subcutaneous locations (n = 31), 27,51,69,92–94,112,115,120,133,135,145,147,156,157,171,212–225 the peritoneal cavity (n = 19), 18,26,56,63,65–68,101,134,135,173,195,226–232 an omental pouch (n = 14), 57,59,81,118,119,163,174,225,233–238 the renal capsule (n = 18), 54,…”

Section: Resultsmentioning

confidence: 99%

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The emerging field of pancreatic tissue engineering: A systematic review and evidence map of scaffold materials and scaffolding techniques for insulin-secreting cells

et al. 2019

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A bioartificial endocrine pancreas is proposed as a future alternative to current treatment options. Patients with insulin-secretion deficiency might benefit. This is the first systematic review that provides an overview of scaffold materials and techniques for insulin-secreting cells or cells to be differentiated into insulin-secreting cells. An electronic literature survey was conducted in PubMed/MEDLINE and Web of Science, limited to the past 10 years. A total of 197 articles investigating 60 different materials met the inclusion criteria. The extracted data on materials, cell types, study design, and transplantation sites were plotted into two evidence gap maps. Integral parts of the tissue engineering network such as fabrication technique, extracellular matrix, vascularization, immunoprotection, suitable transplantation sites, and the use of stem cells are highlighted. This systematic review provides an evidence-based structure for future studies. Accumulating evidence shows that scaffold-based tissue engineering can enhance the viability and function or differentiation of insulin-secreting cells both in vitro and in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The emerging field of pancreatic tissue engineering: A systematic review and evidence map of scaffold materials and scaffolding techniques for insulin-secreting cells

et al. 2019

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“…While numerous protocols have been established, the in vitro production of β-cells can result in a heterogenous population consisting of polyhormonal endocrine cells in addition to monohormonal β-cells. Moreover, the transplantation of these insulin-producing β-cells does not result in all recipients returning to normoglycemia[12, 13], indicating the need to more consistently and efficiently promote maturation of insulin-producing β-cells [17, 21]. Consistent and efficient methods for differentiation to monohormonal β-cells are required for clinical translation to treat T1D.…”

Section: Introductionmentioning

confidence: 99%

Microporous scaffolds drive assembly and maturation of progenitors into β-cell clusters

et al. 2019

Preprint

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Human pluripotent stem cells (hPSCs) represent a promising cell source for the development of β -cells for use in therapies for type 1 diabetes. Current culture approaches provide the signals to drive differentiation towards β -cells, with the cells spontaneously assembling into clusters. Herein, we adapted the current culture systems to cells seeded on microporous biomaterials, with the hypothesis that the pores can guide the assembly into β -cell clusters of defined size that can enhance maturation. The microporous scaffold culture allows hPSC-derived pancreatic progenitors to form clusters at a consistent size as cells undergo differentiation to immature β -cells. By modulating the scaffold pore sizes, we observed 250-425 µm pore size scaffolds significantly enhance insulin expression and key β -cell maturation markers compared to suspension cultures. Furthermore, when compared to suspension cultures, the scaffold culture showed increased insulin secretion in response to glucose stimulus indicating the development of functional β -cells. In addition, scaffolds facilitated cell-cell interactions enabled by the scaffold design and cell-mediated matrix deposition of extracellular matrix (ECM) proteins associated with the basement membrane of islet cells. We further investigated the influence of ECM on cell development by incorporating an ECM matrix on the scaffold prior to cell seeding; however, their presence did not further enhance maturation. These results suggest the microporous scaffold culture facilitates 3D cluster formation, supports cellcell interactions, and provides a matrix similar to a basement membrane to drive in vitro hPSCderived β -cell maturation and demonstrates the feasibility of these scaffolds as a biomanufacturing platform.

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“…[21,70,73,129] Biomaterials more specifically scaffolds can also be employed to promote tissue structure. For instance, many epithelial-derived organoids contain tube-like structures such as the lung airway and intestine.…”

Section: Alveolar Organoidsmentioning

confidence: 99%

“…[71,72] Reports are beginning to emerge with the transplantation of hPSC-derived immature beta cells on microporous PLGA and PLLA scaffolds, but thus far have only reported some beta cell maturation in vivo and a short rescue of normoglycemia in diabetic mice. [70,73,74] Acinar and ductal organoids…”

Section: Islet Organoidsmentioning

confidence: 99%

Take a deep breath and digest the material: organoids and biomaterials of the respiratory and digestive systems

et al. 2017

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Human organoid models recapitulate many aspects of the complex composition and function of native organs. One of the main challenges in developing these models is the growth and maintenance of three-dimensional tissue structures and proper cellular organization that enable function. Biomaterials play an important role by providing a defined and tunable three-dimensional environment that is required for complex cellular organization and organoid growth in vitro or in vivo. This review summarizes organoids of the respiratory and digestive system, and the use of biomaterials to improve upon these model systems.

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The effect of endothelial cells on hESC-derived pancreatic progenitors in a 3D environment

Abstract: A 3D co-culture system of hESC-derived pancreatic progenitors and ECs that would take advantage of the potentially positive effects of ECs.

Cited by 16 publications

References 26 publications

The emerging field of pancreatic tissue engineering: A systematic review and evidence map of scaffold materials and scaffolding techniques for insulin-secreting cells

The emerging field of pancreatic tissue engineering: A systematic review and evidence map of scaffold materials and scaffolding techniques for insulin-secreting cells

Microporous scaffolds drive assembly and maturation of progenitors into β-cell clusters

Take a deep breath and digest the material: organoids and biomaterials of the respiratory and digestive systems

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