A synopsis of factors regulating beta cell development and beta cell mass

Prasadan, Krishna; Shiota, Chiyo; Xiao, Xianmin; Ricks, David M.; Fusco, Joseph; Gittes, George K.

doi:10.1007/s00018-016-2231-0

Cited by 12 publications

(8 citation statements)

References 118 publications

(158 reference statements)

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“…Although comprehensive comparison between the adult and fetal pancreas ECM has not been made, it is well established that changes in gene and protein expression accompany functional changes as β cells mature. − Given the dynamic changes in the ECM that occur during development, we chose to expand our techniques and explore the utilization of label-free approach to identify differences in the ECM between the fetal pancreas and adult pancreas. A recently optimized data-dependent acquisition (DDA) method was employed to enable in-depth analysis of the pancreatic proteome without offline fractionation or extending the gradient time .…”

Section: Resultsmentioning

confidence: 99%

In Depth Quantification of Extracellular Matrix Proteins from Human Pancreas

Tremmel

et al. 2019

J. Proteome Res.

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Extracellular matrix (ECM) is an important component of the pancreatic microenvironment which regulates β cell proliferation, differentiation, and insulin secretion. Protocols have recently been developed for the decellularization of the human pancreas to generate functional scaffolds and hydrogels. In this work, we characterized human pancreatic ECM composition before and after decellularization using isobaric dimethylated leucine (DiLeu) labeling for relative quantification of ECM proteins. A novel correction factor was employed in the study to eliminate the bias introduced during sample preparation. In comparison to the commonly employed sample preparation methods (urea and FASP) for proteomic analysis, a recently developed surfactant and chaotropic agent assisted sequential extraction/on pellet digestion (SCAD) protocol has provided an improved strategy for ECM protein extraction of human pancreatic ECM matrix. The quantitative proteomic results revealed the preservation of matrisome proteins while most of the cellular proteins were removed. This method was compared with a well-established label-free quantification (LFQ) approach which rendered similar expressions of different categories of proteins (collagens, ECM glycoproteins, proteoglycans, etc.). The distinct expression of ECM proteins was quantified comparing adult and fetal pancreas ECM, shedding light on the correlation between matrix composition and postnatal β cell maturation. Despite the distinct profiles of *

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Section: Resultsmentioning

confidence: 99%

In Depth Quantification of Extracellular Matrix Proteins from Human Pancreas

Tremmel

et al. 2019

J. Proteome Res.

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“…Moreover, it is believed that VEGF (vascular endothelial growth factor) is predominantly secreted by β-cells in adult pancreas, affecting islet function and physiology [173]. Consequently, exogenous supplementation with VEGF has been associated with reduction in β-cell apoptosis and maintenance of β-cell mass [174].…”

Section: Mature β-Cellsmentioning

confidence: 99%

Stem cells differentiation into insulin-producing cells (IPCs): recent advances and current challenges

et al. 2022

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Type 1 diabetes mellitus (T1D) is a chronic disease characterized by an autoimmune destruction of insulin-producing β-pancreatic cells. Although many advances have been achieved in T1D treatment, current therapy strategies are often unable to maintain perfect control of glycemic levels. Several studies are searching for new and improved methodologies for expansion of β-cell cultures in vitro to increase the supply of these cells for pancreatic islets replacement therapy. A promising approach consists of differentiation of stem cells into insulin-producing cells (IPCs) in sufficient number and functional status to be transplanted. Differentiation protocols have been designed using consecutive cytokines or signaling modulator treatments, at specific dosages, to activate or inhibit the main signaling pathways that control the differentiation of induced pluripotent stem cells (iPSCs) into pancreatic β-cells. Here, we provide an overview of the current approaches and achievements in obtaining stem cell-derived β-cells and the numerous challenges, which still need to be overcome to achieve this goal. Clinical translation of stem cells-derived β-cells for efficient maintenance of long-term euglycemia remains a major issue. Therefore, research efforts have been directed to the final steps of in vitro differentiation, aiming at production of functional and mature β-cells and integration of interdisciplinary fields to generate efficient cell therapy strategies capable of reversing the clinical outcome of T1D.

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“…The signaling is initiated through the phosphorylation of smad proteins in the cytoplasmic and the translocation of this protein into the nucleus to alter gene transcription. Short-term inhibition of smad2/3 in the cell culture induced Nkx2.2-positive cells and promoted the maturation of endocrine cells (126). In pancreas development, notch signaling also regulates the cell fate.…”

Section: Generating Ipcsmentioning

confidence: 99%

Insulin-Producing Cell Transplantation Platform for Veterinary Practice

et al. 2020

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Diabetes mellitus (DM) remains a global concern in both human and veterinary medicine. Type I DM requires prolonged and consistent exogenous insulin administration to address hyperglycemia, which can increase the risk of diabetes complications such as retinopathy, nephropathy, neuropathy, and heart disorders. Cell-based therapies have been successful in human medicine using the Edmonton protocol. These therapies help maintain the production of endogenous insulin and stabilize blood glucose levels and may possibly be adapted to veterinary clinical practice. The limited number of cadaveric pancreas donors and the long-term use of immunosuppressive agents are the main obstacles for this protocol. Over the past decade, the development of potential therapies for DM has mainly focused on the generation of effective insulin-producing cells (IPCs) from various sources of stem cells that can be transplanted into the body. Another successful application of stem cells in type I DM therapies is transplanting generated IPCs. Encapsulation can be an alternative strategy to protect IPCs from rejection by the body due to their immunoisolation properties. This review summarizes current concepts of IPCs and encapsulation technology for veterinary clinical application and proposes a potential stem-cell-based platform for veterinary diabetic regenerative therapy.

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A synopsis of factors regulating beta cell development and beta cell mass

Cited by 12 publications

References 118 publications

In Depth Quantification of Extracellular Matrix Proteins from Human Pancreas

In Depth Quantification of Extracellular Matrix Proteins from Human Pancreas

Stem cells differentiation into insulin-producing cells (IPCs): recent advances and current challenges

Insulin-Producing Cell Transplantation Platform for Veterinary Practice

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