Hospital time prior to death and pancreas histopathology: implications for future studies
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Diabetes research studies routinely rely upon the use of tissue samples from human organ donors. It remains unclear whether the length of hospital stay prior to organ donation affects the presence of cells infiltrating the pancreas or the frequency of replicating beta cells.
To address this, 39 organ donors without diabetes were matched for age, sex, BMI and ethnicity in groups of three. Within each group, donors varied by length of hospital stay immediately prior to organ donation (<3 days, 3 to <6 days, or ≥6 days). Serial sections from tissue blocks in the pancreas head, body and tail regions were immunohistochemically double stained for insulin and CD45, CD68, or Ki67. Slides were electronically scanned and quantitatively analysed for cell positivity.
No differences in CD45+, CD68+, insulin+, Ki67+ or Ki67+/insulin+ cell frequencies were found when donors were grouped according to duration of hospital stay. Likewise, no interactions were observed between hospitalisation group and pancreas region, age, or both; however, with Ki67 staining, cell frequencies were greater in the body vs the tail region of the pancreas (∆ 0.65 [unadjusted 95% CI 0.25, 1.04]; p = 0.002) from donors <12 year of age. Interestingly, frequencies were less in the body vs tail region of the pancreas for both CD45+ cells (∆ −0.91 [95% CI −1.71, −0.10]; p = 0.024) and insulin+ cells (∆ −0.72 [95% CI −1.10, −0.34]; p < 0.001).
This study suggests that immune or replicating beta cell frequencies are not affected by the length of hospital stay prior to donor death in pancreases used for research.
All referenced macros (adopted and developed), calculations, programming code and numerical dataset files (including individual-level donor data) are freely available on GitHub through Zenodo at https://doi.org/10.5281/zenodo.1034422
KeywordsBasic science Clinical science Human Imaging (MRI/PET/other) Islets Islets(all) Pathophysiology/metabolism
Network for Pancreatic Organ Donors with Diabetes
The authors thank A. Posgai (Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA) for editing and formatting the manuscript. Some of the data from this study was previously presented at the 9th annual JDRF nPOD Scientific Meeting in February 2017. Organ Procurement Organizations (OPO) partnering with nPOD to provide research resources are listed at http://www.jdrfnpod.org/for-partners/npod-partners. Our deepest apologies go to those colleagues whose work was not cited, or cited and not discussed in detail.
Jupyter Notebooks have been prepared to allow reproduction of all aspects of this study, including the matching process, pilot data analysis, power calculations, dataset preparation, statistical analysis and figure generation. All referenced macros (adopted and developed), calculations, programming code and numerical dataset files (including individual-level donor data) are freely available on GitHub through Zenodo at https://doi.org/10.5281/zenodo.1034422
This research was performed with the support of the nPOD, a collaborative type 1 diabetes research project, and was sponsored by the JDRF (25-2013-268, 25-2012-380, and 25-2007-874 to MAA, including a subcontract to JSK). Funding was also provided by the National Institutes of Health Human Islet Research Network (NIH HIRN, U01DK104147 to JSK) and a program project grant (P01 AI42288 to MAA).
Duality of interest
MAA and AP serve as executive directors of the nPOD program and JSK directs its data management core. All other authors declare that there is no duality of interest associated with their contribution to this manuscript.
IK conceived of the study, acquired and interpreted data and drafted and edited the manuscript. MB acquired and interpreted data. TP, SS and CW acquired data. AM analysed and interpreted data and edited the manuscript. PJ contributed to the conception of the study. AP, DS and JAL interpreted the data. MAA conceived of the study and edited the manuscript. JSK conceived of the study, analysed and interpreted the data and drafted and edited the manuscript. All authors critically reviewed the manuscript and approved the final version. JSK is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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