Superporous agarose scaffolds for encapsulation of adult human islets and human stem‐cell‐derived β cells for intravascular bioartificial pancreas applications

2021 ◽  
Author(s):  
Rebecca Shaheen ◽  
Rachel E. Gurlin ◽  
Rebecca Gologorsky ◽  
Charles Blaha ◽  
Pujita Munnangi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Islets ◽  
Human Stem Cell ◽  
Bioartificial Pancreas ◽  
Β Cells ◽  
Adult Human

scholarly journals Proteomic and Transcriptional Profiles of Human Stem Cell-Derived β Cells Following Enteroviral Challenge

2020 ◽  
Vol 8 (2) ◽  
pp. 295 ◽  
Author(s):  
Julius O. Nyalwidhe ◽  
Agata Jurczyk ◽  
Basanthi Satish ◽  
Sambra Redick ◽  
Natasha Qaisar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ex Vivo ◽  
Human Islets ◽  
Islet Autoimmunity ◽  
Type I ◽  
Human Stem Cell ◽  
Β Cells ◽  
Enteroviral Infection ◽  
Insulin Gene Expression ◽  
New Treatments

Enteroviral infections are implicated in islet autoimmunity and type 1 diabetes (T1D) pathogenesis. Significant β-cell stress and damage occur with viral infection, leading to cells that are dysfunctional and vulnerable to destruction. Human stem cell-derived β (SC-β) cells are insulin-producing cell clusters that closely resemble native β cells. To better understand the events precipitated by enteroviral infection of β cells, we investigated transcriptional and proteomic changes in SC-β cells challenged with coxsackie B virus (CVB). We confirmed infection by demonstrating that viral protein colocalized with insulin-positive SC-β cells by immunostaining. Transcriptome analysis showed a decrease in insulin gene expression following infection, and combined transcriptional and proteomic analysis revealed activation of innate immune pathways, including type I interferon (IFN), IFN-stimulated genes, nuclear factor-kappa B (NF-κB) and downstream inflammatory cytokines, and major histocompatibility complex (MHC) class I. Finally, insulin release by CVB4-infected SC-β cells was impaired. These transcriptional, proteomic, and functional findings are in agreement with responses in primary human islets infected with CVB ex vivo. Human SC-β cells may serve as a surrogate for primary human islets in virus-induced diabetes models. Because human SC-β cells are more genetically tractable and accessible than primary islets, they may provide a preferred platform for investigating T1D pathogenesis and developing new treatments.

scholarly journals Evidence for the presence of stem cell-like progenitor cells in human adult pancreas

2007 ◽  
Vol 195 (3) ◽  
pp. 407-414 ◽  
Author(s):  
Min Zhao ◽  
Stephanie A Amiel ◽  
Michael R Christie ◽  
Paolo Muiesan ◽  
Parthi Srinivasan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adult Life ◽  
Stem Cell Markers ◽  
Human Pancreas ◽  
Β Cells ◽  
Adult Human ◽  
Pancreatic Cells ◽  
Exocrine Cell ◽  
Cell Fractions ◽  
Unique Cell

The origin of cells replacing ageing β-cells in adult life is unknown. This study assessed the expression of classic stem cell markers: Oct4, Sox2 and CD34 in islet-enriched fractions versus exocrine cell-enriched fractions from 25 adult human pancreases following human islet isolation. Expression of Oct4, Sox2 and CD34 mRNAs was found in all cell samples, with no significant differences between endocrine and exocrine cell fractions. Immunohistochemical staining for Oct4, Sox2, CD133, CD34, CK19, insulin and nestin on human pancreas sections showed that the majority of Oct4+ve cells were found in the walls of small ducts. Similar localisations were observed for Sox2+ve cells. The majority of Sox2+ve cells were found to co-express Oct4 proteins, but not vice versa. Cells positive for Oct4 and Sox2 appeared to be a unique cell population in the adult human pancreases without co-expression for CK19, CD34, CD133, insulin and nestin proteins. The numbers of Oct4+ve and Sox2+ve cells varied among donors and were ∼1–200 and 1–30 per 100 000 pancreatic cells respectively.

scholarly journals Pluripotency-associated stem cell marker expression in proliferative cell cultures derived from adult human pancreas

2011 ◽  
Vol 211 (2) ◽  
pp. 169-176 ◽  
Author(s):  
Michael G White ◽  
Hussain R Al-Turaifi ◽  
Graham N Holliman ◽  
Ali Aldibbiat ◽  
Aiman Mahmoud ◽  
...  
Keyword(s):  
Stem Cell ◽  
Western Blot ◽  
Gradient Centrifugation ◽  
Stem Cell Marker ◽  
Stem Cell Markers ◽  
Human Pancreas ◽  
Cell Marker ◽  
Β Cells ◽  
Pancreatic Cell ◽  
Adult Human

The source of new β-cells in adult human pancreas remains incompletely elucidated with recent studies on rodents providing evidence for neogenesis from progenitor cells in addition to self-replication. The aim of this study was to investigate the expression of pluripotency-associated stem cell markers in proliferative cultures derived from adult human pancreas. Human pancreatic tissue was obtained from deceased donors following ethical approval and relative consent. Islet-enriched fraction was separated from the retrieved organ by digestion and density gradient centrifugation. Dissociated cells were seeded in adherent culture forming proliferative ‘islet survivor cells’ (ISCs). These were characterised at fifth passage by RT-PCR, immunofluorescence staining, FACS, western blot and transfection studies with an OCT4 promoter-driven reporter. Nuclear expression of the pluripotency-associated stem cell marker complex OCT4/SOX2/NANOG was confirmed in ISCs. The phenotype constituted ∼8% of the overall population. OCT4 biosynthesis was confirmed by western blot and activation of an exogenous OCT4 promoter. Co-expression of pluripotency-associated markers has been confirmed in proliferative primary cells derived from adult human pancreas. Further studies are required to elucidate whether these cells possess functional stem cell characteristics and assess potential for differentiation into pancreatic cell lineages including new β-cells.

scholarly journals Acquisition of Dynamic Function in Human Stem Cell-Derived β Cells

2019 ◽  
Vol 12 (2) ◽  
pp. 351-365 ◽  
Author(s):  
Leonardo Velazco-Cruz ◽  
Jiwon Song ◽  
Kristina G. Maxwell ◽  
Madeleine M. Goedegebuure ◽  
Punn Augsornworawat ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Stem Cell ◽  
Β Cells ◽  
Dynamic Function

scholarly journals Screening enteroviruses for β-cell tropism using foetal porcine β-cells

2001 ◽  
Vol 82 (8) ◽  
pp. 1909-1916 ◽  
Author(s):  
Merja Roivainen ◽  
Petri Ylipaasto ◽  
Jarkko Ustinov ◽  
Tapani Hovi ◽  
Timo Otonkoski
Keyword(s):  
Cell Function ◽  
Biological Properties ◽  
Human Islets ◽  
Cell Tropism ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Systematic Screening ◽  
Adult Human ◽  
Β Cell Function

Primary adult human insulin-producing β-cells are susceptible to infection by prototype strains of coxsackieviruses (CV) and infection may result in impaired β-cell function and/or cell death, as shown for coxsackie B virus (CVB) types 4 and 5, or have no apparent immediate adverse effects, as shown for CVA-9. Because of the limited availability of human pancreatic β-cells, the aim of this study was to find out if foetal porcine pancreatic islets could be used as a substitute in enterovirus (EV) screening. These cells resemble human β-cells in several biological properties. CVB infection resulted in a rapid progressive decline of insulin content and reponsiveness to insulin release. The amount of virus inoculum sufficient for this destruction was small, corresponding to only 55 infectious units per pancreas. In contrast to CVBs, CVA-9 replicated poorly, and sometimes not at all, in foetal porcine β-cells. The first signs of functional impairment and cell destruction, if present at all, were seen only after 1–3 weeks of incubation. Furthermore, CVA-16, several strains of echoviruses and human parechovirus type 1 were unable to replicate in foetal porcine pancreatic β-cells. Based on these results, foetal porcine islets are somewhat more sensitive to CVB infection than adult human islets, whereas many other human EV strains do not infect porcine β-cells. Therefore, foetal porcine β-cells cannot be used for systematic screening of human EV strains and isolates for β-cell tropism, but they might provide a useful model for detailed studies on the interaction of CVBs with β-cells.

scholarly journals Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived β cells

2019 ◽  
Vol 21 (2) ◽  
pp. 263-274 ◽  
Author(s):  
Gopika G. Nair ◽  
Jennifer S. Liu ◽  
Holger A. Russ ◽  
Stella Tran ◽  
Michael S. Saxton ◽  
...  
Keyword(s):  
Stem Cell ◽  
Endocrine Cell ◽  
Human Stem Cell ◽  
Β Cells ◽  
Cell Clustering
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