The New Generation of Beta-Cells: Replication, Stem Cell Differentiation, and the Role of Small Molecules

Borowiak, Malgorzata

doi:10.1900/rds.2010.7.93

Cited by 17 publications

(22 citation statements)

References 82 publications

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“…These various types of stem cells, especially human ESCs (hESCs) and human iPSCs (hiPSCs), have enormous potential for the study of human development and disease. For instance, hPSCs have been differentiated into diverse cell types such as cardiomyocytes [82], beta-pancreatic cells [83], neurons and glia [84], retina [85], and even three-dimensional structures such as the optic cup [86], typically by directed manipulation of intracellular and extracellular signaling pathways via protein or small molecule treatments, intercellular interactions, mechanotransduction, or matrix-mediated cues [87] (Figure 3). These differentiation protocols allow access to cell populations, including transient developmental progenitors and terminally differentiated cells that would otherwise be unattainable from human tissue.…”

Section: Reviewmentioning

confidence: 99%

Modeling the blood–brain barrier using stem cell sources

Lippmann

Al‐Ahmad

Palecek

et al. 2013

Fluids Barriers CNS

111

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The blood–brain barrier (BBB) is a selective endothelial interface that controls trafficking between the bloodstream and brain interstitial space. During development, the BBB arises as a result of complex multicellular interactions between immature endothelial cells and neural progenitors, neurons, radial glia, and pericytes. As the brain develops, astrocytes and pericytes further contribute to BBB induction and maintenance of the BBB phenotype. Because BBB development, maintenance, and disease states are difficult and time-consuming to study in vivo, researchers often utilize in vitro models for simplified analyses and higher throughput. The in vitro format also provides a platform for screening brain-penetrating therapeutics. However, BBB models derived from adult tissue, especially human sources, have been hampered by limited cell availability and model fidelity. Furthermore, BBB endothelium is very difficult if not impossible to isolate from embryonic animal or human brain, restricting capabilities to model BBB development in vitro. In an effort to address some of these shortcomings, advances in stem cell research have recently been leveraged for improving our understanding of BBB development and function. Stem cells, which are defined by their capacity to expand by self-renewal, can be coaxed to form various somatic cell types and could in principle be very attractive for BBB modeling applications. In this review, we will describe how neural progenitor cells (NPCs), the in vitro precursors to neurons, astrocytes, and oligodendrocytes, can be used to study BBB induction. Next, we will detail how these same NPCs can be differentiated to more mature populations of neurons and astrocytes and profile their use in co-culture modeling of the adult BBB. Finally, we will describe our recent efforts in differentiating human pluripotent stem cells (hPSCs) to endothelial cells with robust BBB characteristics and detail how these cells could ultimately be used to study BBB development and maintenance, to model neurological disease, and to screen neuropharmaceuticals.

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Section: Reviewmentioning

confidence: 99%

Modeling the blood–brain barrier using stem cell sources

Lippmann

Al‐Ahmad

Palecek

et al. 2013

Fluids Barriers CNS

111

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“…To overcome these limits and achieve customization and scalability, we developed a new 3D printed NG using biocompatible functionalized polymers, fillable with ECM-like PL gel matrix to better nurture the pancreatic islets or other insulin secreting cells, such as ILIPAs, derived by MSCs or other sources. 32 …”

Section: Discussionmentioning

confidence: 99%

Three-dimensional printed polymeric system to encapsulate human mesenchymal stem cells differentiated into islet-like insulin-producing aggregates for diabetes treatment

et al. 2016

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Diabetes is one of the most prevalent, costly, and debilitating diseases in the world. Pancreas and islet transplants have shown success in re-establishing glucose control and reversing diabetic complications. However, both are limited by donor availability, need for continuous immunosuppression, loss of transplanted tissue due to dispersion, and lack of vascularization. To overcome the limitations of poor islet availability, here, we investigate the potential of bone marrow–derived mesenchymal stem cells differentiated into islet-like insulin-producing aggregates. Islet-like insulin-producing aggregates, characterized by gene expression, are shown to be similar to pancreatic islets and display positive immunostaining for insulin and glucagon. To address the limits of current encapsulation systems, we developed a novel three-dimensional printed, scalable, and potentially refillable polymeric construct (nanogland) to support islet-like insulin-producing aggregates’ survival and function in the host body. In vitro studies showed that encapsulated islet-like insulin-producing aggregates maintained viability and function, producing steady levels of insulin for at least 4 weeks. Nanogland—islet-like insulin-producing aggregate technology here investigated as a proof of concept holds potential as an effective and innovative approach for diabetes cell therapy.

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“…High content chemical screenings have also revealed new small molecules involved in inducing DE cells from ESCs. Borowiak et al reported that IDE1 and IDE2 induced nearly 80% of ESCs to form SOX17expressing DE cells, a higher efficiency than that achieved by activin A or Nodal [20,21]. Studies with Pdx1-eGFP reporter line also confirmed that these DE cells were able to further differentiate into pancreatic progenitors.…”

Section: Generating Definitive Endoderm and Pancreatic Endocrine Cellmentioning

confidence: 96%

Generation of Insulin-Producing Cells From Pluripotent Stem Cells: From the Selection of Cell Sources to the Optimization of Protocols

Liew

2010

Rev Diabet Stud

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The pancreas arises from Pdx1-expressing progenitors in developing foregut endoderm in early embryo. Expression of Ngn3 and NeuroD1 commits the cells to form endocrine pancreas, and to differentiate into subsets of cells that constitute islets of Langerhans. β-cells in the islets transcribe gene-encoding insulin, and subsequently process and secrete insulin, in response to circulating glucose. Dysfunction of β-cells has profound metabolic consequences leading to hyperglycemia and diabetes mellitus. β-cells are destroyed via autoimmune reaction in type 1 diabetes (T1D). Type 2 diabetes (T2D), characterized by impaired β-cell functions and reduced insulin sensitivity, accounts for 90% of all diabetic patients. Islet transplantation is a promising treatment for T1D. Pluripotent stem cells provide an unlimited cell source to generate new β-cells for patients with T1D. Furthermore, derivation of induced pluripotent stem cells (iPSCs) from patients captures "disease-in-a-dish" for autologous cell replacement therapy, disease modeling, and drug screening for both types of diabetes. This review highlights essential steps in pancreas development, and potential stem cell applications in cell regeneration therapy for diabetes mellitus.

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The New Generation of Beta-Cells: Replication, Stem Cell Differentiation, and the Role of Small Molecules

Cited by 17 publications

References 82 publications

Modeling the blood–brain barrier using stem cell sources

Modeling the blood–brain barrier using stem cell sources

Three-dimensional printed polymeric system to encapsulate human mesenchymal stem cells differentiated into islet-like insulin-producing aggregates for diabetes treatment

Generation of Insulin-Producing Cells From Pluripotent Stem Cells: From the Selection of Cell Sources to the Optimization of Protocols

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