Bioreactors Addressing Diabetes Mellitus

Minteer, Danielle M.; Gerlach, Jörg C.; Marra, Kacey G.

doi:10.1177/1932296814548215

Cited by 9 publications

(7 citation statements)

References 48 publications

(88 reference statements)

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“…Defects in adipose tissue are caused by congenital abnormalities, traumatic injuries and tumor resections in various areas of the body and require better tissue engineering strategies for repair [1, 2]. Physiologically relevant and sustainable adipose models will also enhance our understanding of cell biology and provide novel experimental systems in vitro to study metabolism and metabolic disease mechanisms, such as obesity and type II diabetes [3]. …”

Section: Introductionmentioning

confidence: 99%

Long term perfusion system supporting adipogenesis

Abbott

Raja

Wang

et al. 2015

Methods

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Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight.

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Section: Introductionmentioning

confidence: 99%

Long term perfusion system supporting adipogenesis

Abbott

Raja

Wang

et al. 2015

Methods

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“…Confocal laser scanning microscopy (CLSM, Olympus FV1000) was performed to observe live/dead cells. Immunohistochemistry and gene expression analyses were performed according to the manufacturer’s protocol. , …”

Section: Methodsmentioning

confidence: 99%

“…Immunohistochemistry and gene expression analyses were performed according to the manufacturer's protocol. 5,6 2.5. In Vivo Studies.…”

Section: Methodsmentioning

confidence: 99%

Injectable and Self-Adaptive Gel Scaffold Based on Heparin Microspheres for Adipogenesis of Human Adipose-Derived Stem Cells

Zhai,

Tao,

et al. 2023

Biomacromolecules

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An injectable and self-adaptive heparin microsphere-based cell scaffold was developed to achieve adipose regeneration. Simultaneously, the cell scaffold exhibited a dynamic architecture, self-regulated glucose levels, sustained insulin delivery, and steady viscoelastic properties for adipogenesis. The dynamic cell scaffold is cross-linked by the boronate−diol interaction among heparin-based microspheres, which have boronate and maltose groups. Because of the boronate−maltose ester bonds, the gelatinous complex would be partially dismantled and readily display glucose-sensitive performance by free glucose via competitive displacement. The dynamic cross-linking heparin microsphere scaffold can deliver the lipogenic drug insulin to enhance lipid filling, which has an impact on fat tissue enhancement. A 4-week in vitro cell culture demonstrated that the dynamic heparin microsphere-based cell scaffold, through loading with insulin, showed significantly higher efficiency in promoting ASC differentiation compared with traditional 3D culture methods. In vivo histological results further demonstrated that there was a significant increase in adipose in the proposed cell scaffold, which proved to be statistically significant compared with traditional biomaterials. Notable stain expression of the FABP4 and PPAR-γ genes was also observed in the dynamic cell scaffold containing insulin, which was more similar to natural fat.

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“…When cultured directly under high external flow rates, shear stress damages peripheral islet cells, reducing glucose-stimulated metabolism and calcium response ( Shenkman et al, 2009 ; Sankar et al, 2011 ; Silva et al, 2013 ). However, blood flow ( Wang et al, 2010 ) and islet culture in bioreactors ( Minteer et al, 2014 ) also improves mass transfer to pancreatic islets ( Wu et al, 2014 ), improving islet survival and function ( Lock et al, 2011 ; Sankar et al, 2011 ) – particularly if the islets are protected from shear stress ( Jun et al, 2019 ). Islets with endothelial cells co-cultured under external flow have higher endothelial cell survival compared to static culture which may improve islet functionality and health ex vivo , perhaps by mediating regeneration of islet ECM within aggregates ( Sankar et al, 2011 ; Jun et al, 2019 ).…”

Section: Cell–matrix Interactionsmentioning

confidence: 99%

Developmentally-Inspired Biomimetic Culture Models to Produce Functional Islet-Like Cells From Pluripotent Precursors

Tran

Moraes

Hoesli

2020

Front. Bioeng. Biotechnol.

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Insulin-producing beta cells sourced from pluripotent stem cells hold great potential as a virtually unlimited cell source to treat diabetes. Directed pancreatic differentiation protocols aim to mimic various stimuli present during embryonic development through sequential changes of in vitro culture conditions. This is commonly accomplished by the timed addition of soluble signaling factors, in conjunction with cell-handling steps such as the formation of 3D cell aggregates. Interestingly, when stem cells at the pancreatic progenitor stage are transplanted, they form functional insulinproducing cells, suggesting that in vivo microenvironmental cues promote beta cell specification. Among these cues, biophysical stimuli have only recently emerged in the context of optimizing pancreatic differentiation protocols. This review focuses on studies of cell-microenvironment interactions and their impact on differentiating pancreatic cells when considering cell signaling, cell-cell and cell-ECM interactions. We highlight the development of in vitro cell culture models that allow systematic studies of pancreatic cell mechanobiology in response to extracellular matrix proteins, biomechanical effects, soluble factor modulation of biomechanics, substrate stiffness, fluid flow and topography. Finally, we explore how these new mechanical insights could lead to novel pancreatic differentiation protocols that improve efficiency, maturity, and throughput.

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Bioreactors Addressing Diabetes Mellitus

Cited by 9 publications

References 48 publications

Long term perfusion system supporting adipogenesis

Long term perfusion system supporting adipogenesis

Injectable and Self-Adaptive Gel Scaffold Based on Heparin Microspheres for Adipogenesis of Human Adipose-Derived Stem Cells

Developmentally-Inspired Biomimetic Culture Models to Produce Functional Islet-Like Cells From Pluripotent Precursors

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