TY - JOUR
T1 - Hospital time prior to death and pancreas histopathology
T2 - implications for future studies
AU - Kusmartseva, Irina
AU - Beery, Maria
AU - Philips, Tiffany
AU - Selman, Stephen
AU - Jadhav, Priyanka
AU - Wasserfall, Clive
AU - Muller, Axel
AU - Pugliese, Alberto
AU - Longmate, Jeffrey A.
AU - Schatz, Desmond A.
AU - Atkinson, Mark A.
AU - Kaddis, John S.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Aims/hypothesis: 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. Methods: 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 (OpenSPiltSPi3 days, 3 to OpenSPiltSPi6 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. Results: 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 OpenSPiltSPi12 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 OpenSPiltSPi 0.001). Conclusions/interpretation: 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. Data availability: 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.
AB - Aims/hypothesis: 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. Methods: 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 (OpenSPiltSPi3 days, 3 to OpenSPiltSPi6 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. Results: 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 OpenSPiltSPi12 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 OpenSPiltSPi 0.001). Conclusions/interpretation: 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. Data availability: 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.
KW - Basic science
KW - Clinical science
KW - Human
KW - Imaging (MRI/PET/other)
KW - Islets
KW - Islets(all)
KW - Pathophysiology/metabolism
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U2 - 10.1007/s00125-017-4494-x
DO - 10.1007/s00125-017-4494-x
M3 - Article
C2 - 29128936
AN - SCOPUS:85033437982
VL - 61
SP - 954
EP - 958
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 4
ER -