scholarly journals NIH Initiative to Improve Understanding of the Pancreas, Islet, and Autoimmunity in Type 1 Diabetes: The Human Pancreas Analysis Program (HPAP)

Diabetes ◽  
2019 ◽  
Vol 68 (7) ◽  
pp. 1394-1402 ◽  
Author(s):  
Klaus H. Kaestner ◽  
Alvin C. Powers ◽  
Ali Naji ◽  
Mark A. Atkinson ◽  
Keyword(s):  
Type 1 Diabetes ◽  
Human Pancreas ◽  
Analysis Program ◽  
Pancreas Islet

scholarly journals Substance Use Affects Type 1 Diabetes Pancreas Pathology: Implications for Future Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Brittany S. Bruggeman ◽  
Martha Campbell-Thompson ◽  
Stephanie L. Filipp ◽  
Matthew J. Gurka ◽  
Mark A. Atkinson ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Substance Use ◽  
Type 1 Diabetes ◽  
Chronic Pancreatitis ◽  
Fatty Infiltration ◽  
Organ Donors ◽  
Human Pancreas ◽  
Islet Amyloid ◽  
Control Organ

Access to human pancreas samples from organ donors has greatly advanced our understanding of type 1 diabetes pathogenesis; however, previous studies have shown that donors have a high rate of substance use, and its impact on pancreatic histopathology in this disease is not well described. One-hundred-thirty-one type 1 diabetes and 111 control organ donor pancreata from persons 12-89 years of age (mean 29.8 ± 15.5 years) within the Network for Pancreatic Organ donors with Diabetes (nPOD) were examined for insulin positivity, insulitis, amyloid staining, acute and chronic pancreatitis, and chronic exocrine changes (acinar atrophy, fibrosis, fatty infiltration, or periductal fibrosis); findings were compared by history of substance use. A secondary analysis compared exocrine pancreatic histopathologic findings in type 1 diabetes versus control organ donors regardless of substance use history. We observed a high but congruent rate of substance use in type 1 diabetes and control organ donors (66.4% and 64% respectively). Among donors with type 1 diabetes (but not controls), islet amyloid (OR 9.96 [1.22, 81.29]) and acute pancreatitis (OR 3.2 [1.06, 9.63]) were more common in alcohol users while chronic exocrine changes (OR 8.86 [1.13, 69.31]) were more common in cocaine users. Substance use impacted the pancreata of donors with type 1 diabetes more than controls. Overall, despite similar rates of substance use, acute pancreatitis (15.3% versus 4.5%, p=0.0061), chronic pancreatitis (29.8% versus 9.9%, p=0.0001), and chronic exocrine changes (73.3% versus 36.9%, p<0.0001) were more common in type 1 diabetes donors than controls. Alcohol and/or cocaine use in type 1 diabetes organ donors increases exocrine pancreas pathology and islet amyloid deposition but does not affect insulitis or insulin positivity. Exocrine pathology in type 1 diabetes donors is common, and further study of the pathophysiology of these changes is needed.

scholarly journals Proteomic Analysis of Disease Stratified Human Pancreas Tissue Indicates Unique Signature of Type 1 Diabetes

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135663 ◽  
Author(s):  
Tanya C. Burch ◽  
Margaret A. Morris ◽  
Martha Campbell-Thompson ◽  
Alberto Pugliese ◽  
Jerry L. Nadler ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Proteomic Analysis ◽  
Human Pancreas ◽  
Unique Signature

scholarly journals Pluripotent Stem Cell-Derived Pancreatic Progenitors and β-Like Cells for Type 1 Diabetes Treatment

Physiology ◽  
2018 ◽  
Vol 33 (6) ◽  
pp. 394-402 ◽  
Author(s):  
Rangarajan Sambathkumar ◽  
Adriana Migliorini ◽  
Maria Cristina Nostro
Keyword(s):  
Type 1 Diabetes ◽  
Pluripotent Stem Cells ◽  
Specific Cell ◽  
Human Pancreas ◽  
Cell Replacement Therapy ◽  
Pancreatic Progenitors ◽  
Specific Cell Surface

In this review, we focus on the processes guiding human pancreas development and provide an update on methods to efficiently generate pancreatic progenitors (PPs) and β-like cells in vitro from human pluripotent stem cells (hPSCs). Furthermore, we assess the strengths and weaknesses of using PPs and β-like cell for cell replacement therapy for the treatment of Type 1 diabetes with respect to cell manufacturing, engrafting, functionality, and safety. Finally, we discuss the identification and use of specific cell surface markers to generate safer populations of PPs for clinical translation and to study the development of PPs in vivo and in vitro.

Pancreas Islet Transplantation in Patients With Type 1 Diabetes Mellitus After Kidney Transplantation

2005 ◽  
Vol 37 (3) ◽  
pp. 1443-1445 ◽  
Author(s):  
M. Gonzalez Molina ◽  
A. Alonso ◽  
R. Briones ◽  
N. Fernandez ◽  
A. Caballero ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Kidney Transplantation ◽  
Type 1 Diabetes Mellitus ◽  
Islet Transplantation ◽  
Pancreas Islet

scholarly journals Multiomics single-cell analysis of human pancreatic islets reveals novel cellular states in health and type 1 diabetes

2021 ◽  
Author(s):  
Maria Fasolino ◽  
Gregory W. Schwartz ◽  
Maria L. Golson ◽  
Yue J. Wang ◽  
Ashleigh Morgan ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Single Cell ◽  
Pancreatic Islets ◽  
Mhc Class Ii ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Human Pancreas ◽  
Analytical Strategy ◽  
Ductal Cells

AbstractType 1 diabetes (T1D) is an autoimmune disease of only partially defined etiology in which immune cells destroy insulin-producing beta cells. Using single-cell transcriptomics and an advanced analytical strategy to assess pancreatic islets of T1D, autoantibody-positive, and non-diabetic organ donors, we identified both canonical cell types and rare insulin-expressing cells with a hybrid mixture of endocrine and exocrine gene signatures within all donors. We further found elevated expression of MHC Class II pathway genes in exocrine ductal cells of T1D donors, which we confirmed through CyTOF, in situ imaging mass cytometry, and immunofluorescence analysis. Taken together, our multimodal analyses identify novel cell types and processes that may contribute to T1D immunopathogenesis and provide new cellular and molecular insights into human pancreas function.

scholarly journals Overview of Cellular Transplantation in Diabetes Mellitus: Focus on the Metabolic Outcome

2015 ◽  
Vol 2015 ◽  
pp. 1-8
Author(s):  
Livio Luzi ◽  
Stefano Benedini ◽  
Andrea Caumo ◽  
Ileana Terruzzi
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Islet Transplantation ◽  
Immunosuppressive Drugs ◽  
Cell Therapies ◽  
Cellular Transplantation ◽  
Major Disadvantage ◽  
Pancreas Islet

Diabetes mellitus is a metabolic disease possible to treat via several different therapeutic approaches. Since the advent of insulin in 1922, type 1 diabetes mellitus has become a chronic treatable disease. Nonetheless, type 1 diabetes mellitus can be a devastating disease when the macro- and microangiopathic complications take place after several years of illness. Starting from the eighties, pancreas/islet transplantation has become a potential innovative treatment of diabetes mellitus. The major advantage of pancreas/islet transplantation is the restoration of c-peptide cosecretion along with insulin; the major disadvantage is the need to administer immunosuppressive drugs which are diabetogenic themselves. Islet transplantation is the progenitor of more recent forms of cellular and stem cell therapies which will be reviewed herein. Cellular therapies for diabetes mellitus are still an experimental procedure. Herein we present the actual current achievements and an outlook of close future possible advancements in the area of cellular transplantation for the cure of diabetes mellitus.

scholarly journals The healthy exocrine pancreas contains preproinsulin-specific CD8 T cells that attack islets in type 1 diabetes

2020 ◽  
Vol 6 (42) ◽  
pp. eabc5586 ◽  
Author(s):  
Christine Bender ◽  
Teresa Rodriguez-Calvo ◽  
Natalie Amirian ◽  
Ken T. Coppieters ◽  
Matthias G. von Herrath
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Cd8 T Cells ◽  
Human Pancreas ◽  
Healthy Individuals ◽  
High Frequencies ◽  
Histocompatibility Complex ◽  
Diabetes Development ◽  
Specific Trigger

Preproinsulin (PPI) is presumably a crucial islet autoantigen found in patients with type 1 diabetes (T1D) but is also recognized by CD8+ T cells from healthy individuals. We quantified PPI-specific CD8+ T cells within different areas of the human pancreas from nondiabetic controls, autoantibody-positive donors, and donors with T1D to investigate their role in diabetes development. This spatial cellular quantitation revealed unusually high frequencies of autoreactive CD8+ T cells supporting the hypothesis that PPI is indeed a key autoantigen. To our surprise, PPI-specific CD8+ T cells were already abundantly present in the nondiabetic pancreas, thus questioning the dogma that T1D is caused by defective thymic deletion or systemic immune dysregulation. During T1D development, these cells accumulated in and around islets, indicating that an islet-specific trigger such as up-regulation of major histocompatibility complex class I might be essential to unmask beta cells to the immune system.

scholarly journals Whole-Slide Image Analysis of Human Pancreas Samples to Elucidate the Immunopathogenesis of Type 1 Diabetes Using the QuPath Software

2021 ◽  
Vol 8 ◽  
Author(s):  
Paola S. Apaolaza ◽  
Peristera-Ioanna Petropoulou ◽  
Teresa Rodriguez-Calvo
Keyword(s):  
Type 1 Diabetes ◽  
Image Analysis ◽  
Islets Of Langerhans ◽  
Cell Function ◽  
Immune Cell ◽  
Scientific Discovery ◽  
Morphological Characteristics ◽  
Human Pancreas ◽  
Analysis Tools

Type 1 diabetes is a chronic disease of the pancreas characterized by the loss of insulin-producing beta cells. Access to human pancreas samples for research purposes has been historically limited, restricting pathological analyses to animal models. However, intrinsic differences between animals and humans have made clinical translation very challenging. Recently, human pancreas samples have become available through several biobanks worldwide, and this has opened numerous opportunities for scientific discovery. In addition, the use of new imaging technologies has unraveled many mysteries of the human pancreas not merely in the presence of disease, but also in physiological conditions. Nowadays, multiplex immunofluorescence protocols as well as sophisticated image analysis tools can be employed. Here, we described the use of QuPath—an open-source platform for image analysis—for the investigation of human pancreas samples. We demonstrate that QuPath can be adequately used to analyze whole-slide images with the aim of identifying the islets of Langerhans and define their cellular composition as well as other basic morphological characteristics. In addition, we show that QuPath can identify immune cell populations in the exocrine tissue and islets of Langerhans, accurately localizing and quantifying immune infiltrates in the pancreas. Therefore, we present a tool and analysis pipeline that allows for the accurate characterization of the human pancreas, enabling the study of the anatomical and physiological changes underlying pancreatic diseases such as type 1 diabetes. The standardization and implementation of these analysis tools is of critical importance to understand disease pathogenesis, and may be informative for the design of new therapies aimed at preserving beta cell function and halting the inflammation caused by the immune attack.

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