Decorin improves human pancreatic β-cell function and regulates ECM expression in vitro

Urbanczyk, Max; Jeyagaran, Abiramy; Zbinden, Aline; Lu, Chuan-En; Marzi, Julia; Kuhlburger, Laurence; Nahnsen, Sven; Layland, Shannon L.; Duffy, Garry P.; Schenke‐Layland, Katja

doi:10.1016/j.matbio.2022.12.005

Cited by 10 publications

(3 citation statements)

References 115 publications

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“…The 10-day spheroids, adult donor islets (from the McDonald Laboratory, Alberta, Canada), and 10-week-old fetal tissues (from the University of Tübingen, Tübingen, Germany) were prepared for IF staining, as previously described 40 . Briefly, samples were washed with PBS, fixed in 4% PFA, and embedded in paraffin with a Shandon Citadel 1000 (Thermo Fisher Scientific, Waltham, MA, USA).…”

Section: Immunofluorescence (If) Staining and Quantificationmentioning

confidence: 99%

Forward programming of hiPSCs towards beta-like cells using Ngn3, Pdx1, and MafA

Jeyagaran,

Urbanczyk,

Layland

et al. 2024

Sci Rep

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Transplantation of stem cell-derived β-cells is a promising therapeutic advancement in the treatment of type 1 diabetes mellitus. A current limitation of this approach is the long differentiation timeline that generates a heterogeneous population of pancreatic endocrine cells. To address this limitation, an inducible lentiviral overexpression system of mature β-cell markers was introduced into human induced-pluripotent stem cells (hiPSCs). Following the selection of the successfully transduced hiPSCs, the cells were treated with doxycycline in the pancreatic progenitor induction medium to support their transition toward the pancreatic lineage. Cells cultured with doxycycline presented the markers of interest, NGN3, PDX1, and MAFA, after five days of culture, and glucose-stimulated insulin secretion assays demonstrated that the cells were glucose-responsive in a monolayer culture. When cultured as a spheroid, the markers of interest and insulin secretion in a static glucose-stimulated insulin secretion assay were maintained; however, insulin secretion upon consecutive glucose challenges was limited. Comparison to human fetal and adult donor tissues identified that although the hiPSC-derived spheroids present similar markers to adult insulin-producing cells, they are functionally representative of fetal development. Together, these results suggest that with optimization of the temporal expression of these markers, forward programming of hiPSCs towards insulin-producing cells could be a possible alternative for islet transplantation.

show abstract

Section: Immunofluorescence (If) Staining and Quantificationmentioning

confidence: 99%

Forward programming of hiPSCs towards beta-like cells using Ngn3, Pdx1, and MafA

Jeyagaran,

Urbanczyk,

Layland

et al. 2024

Sci Rep

Self Cite

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“… 219 Decorin can also promote autophagy by chronic suppression of Met bioactivity in trophoblasts. 220 Decorin binds to vascular endothelial growth factor receptor 2 (VEGFR2) resulting in the phosphorylation of AMPK at Thr 172 which among its regulation of a plethora of catabolic processes, is capable of initiating autophagy 221 , 222 , 223 ( Figure 6 A). Concurrently, AMPK phosphorylation results in an attenuation of the mTOR axis, an anti-autophagic coordinator of anabolic pathways.…”

Section: Proteoglycans and Heparanase As Proautophagic Secreted Factorsmentioning

confidence: 99%

Global impact of proteoglycan science on human diseases

Xie,

Schaefer,

Iozzo

2023

iScience

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“…The 10-day spheroids, adult donor islets (from the McDonald Laboratory, Alberta, Canada), and 10-weekold fetal tissues (from the University of Tübingen, Tübingen, Germany) were prepared for IF staining, as previously described [43]. Brie y, samples were washed with PBS, xed in 4% PFA, and embedded in para n with a Shandon Citadel 1000 (Thermo Fisher Scienti c, Waltham, MA, USA).…”

Section: Immuno Uorescence (If) Staining and Quanti Cationmentioning

confidence: 99%

Forward programming of hiPSCs towards beta-like cells using Ngn3, Pdx1, and MafA

Jeyagaran,

Urbanczyk,

Layland

et al. 2023

Preprint

Self Cite

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Transplantation of stem cell-derived β-cells is a promising therapeutic advancement in the treatment of type 1 diabetes mellitus. A current limitation of this approach is the long differentiation timeline of up to two months that generates a heterogeneous population of pancreatic endocrine cells. To address this limitation, an inducible lentiviral overexpression system of mature β-cell markers was introduced into human induced-pluripotent stem cells (hiPSCs). Following selection of the successfully transduced hiPSCs, the cells were treated with doxycycline in pancreatic progenitor induction medium to support their transition towards the pancreatic lineage. Cells cultured with doxycycline presented the markers of interest, NGN3, PDX1, and MAFA, after five days of culture, and glucose-stimulated insulin secretion assays demonstrated that the cells were glucose-responsive in a monolayer culture. When cultured as a spheroid, the markers of interest and insulin secretion in a parallel glucose-stimulated insulin secretion assay were maintained; however, insulin secretion upon consecutive glucose challenges was limited. Comparison to human fetal and adult donor tissues identified that although the hiPSC-derived spheroids present similar markers to adult insulin-producing cells, they are functionally representative of fetal development. Together, these results suggest that with optimization of the temporal expression of these markers, forward programming of hiPSCs towards insulin-producing cells could be a possible alternative for islet transplantation.

show abstract

Decorin improves human pancreatic β-cell function and regulates ECM expression in vitro

Cited by 10 publications

References 115 publications

Forward programming of hiPSCs towards beta-like cells using Ngn3, Pdx1, and MafA

Forward programming of hiPSCs towards beta-like cells using Ngn3, Pdx1, and MafA

Global impact of proteoglycan science on human diseases

Forward programming of hiPSCs towards beta-like cells using Ngn3, Pdx1, and MafA

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