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CSHL
Computational Cell Biology
Islet Assessment
July 2012
Allan J. Ropski
University of Illinois at Chicago
Department of Surgery
Islets of Langerhans
• Islet Potency Index
▫ FDA requirement for use as a biological drug
▫ Sterility, identity, and purity are established
• Reliably predict transplant outcomes
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Glucose-stimulated insulin secretion; β-cell specific
In-vivo streptozotocin treated mice; Potency Index
UIC-MS islet assays
Phase III human clinical trials*; 52-week follow-up
• Microfluidic optimization
▫ Ca2+; Mitochondrial Potential; Insulin release
▫ High-throughput assays
Human Islet Cell Composition
• 6 isolations
• 32 sampled islets
• Ranges
α-cells
β-cells
δ-cells
28 – 75%
10 – 65%
1 – 22%
Assessment of Human Pancreatic Islet Architecture and Composition by Laser Scanning
Confocal Microscopy
Journal of Histochemistry & Cytochemistry; Volume 53(9): 1087–1097, 2005
Marcela Brissova, Michael J. Fowler, Wendell E. Nicholson, Anita Chu, Boaz Hirshberg, David M. Harlan, and Alvin C.
Powers
C
β-Cell
Tr
an
r
2
Zn+
sp
o
rte
Zn+
Glycolysis
High glucose
insulin
granules
Zn+
Zn+
Zn+
Zn+
pyruvate
Zn+
N
Mitochondria
B
Ca2+
ATP
K+
TP
l
K+
-A
K+
nn
e
Ch
a
K+
K+
Ca2+
2+
K+
K+
Ca2+
KATP-dependent depolarization
Ca2+
l
K+
K+
Phase I
Ca
K+
Ca2+
Ca2+
Ca2+
ne
K+
K+
Ca2+
an
l hypopolarization
Zn+
Ch
Time (min)
Insulin secretion
Ca2+
Ca2+
Calcium
concentration
Glucose
Gl
ut
Microfluidic System