136 
Monitoring Stem Cell Research 
TABLE 1: COMPARISON OF INSULIN-PRODUCING CELLS 
DERIVED FROM HUMAN STEM CELLS 
References 
Cell Source: 
Clonally 
Isolated / 
Marked? 
Beta-cell 
markers 
Ultrastructural 
Examination to 
Ensure En- 
dogenous 
Insulin Produc- 
tion 
Glucose- 
responsive 
Insulin 
Secretion? 
In Vivo Studies 
Tumorigenicity? 
Abraham 
et al, 2002 
(46) ; 
Zuiewski 
et al, 2001 
(47) 
Clonally 
isolated 
adult stem 
cells (derived 
from adult 
pancreatic 
islets) 
PDX-1 {+) 
CK-19 (-(-) 
Insulin 
mRNA(-f); 
Insulin protein 
(-(-); No ultra- 
structural 
examination 
Not as- 
sessed 
None 
Not assessed 
Assady 
et al, 
2001(48) 
Clonally 
isolated 
embryonic 
stem cells 
PDX-1 (-): 
GK(+): 
GLUT-2 (-1-) 
Insulin mRNA 
(+) 
Insulin protein 
(-K): No ultra- 
structural 
examination; 
possible insu- 
lin uptake from 
serum 
No 
None 
Not assessed 
Zhao et al, 
2002 (49) 
Uncloned 
cadaver 
islets (cul- 
tured in 
vitro) 
I 
CK-19 (-h) 
Preproinsulin 
mRNA(+); 
Insulin protein 
(+): 
electron mi- 
croscopy 
insulin secre- 
tory granuoles 
(+) 
Yes 
High blood glu- 
cose concentra- 
tions reversed in 
STZ/SCID mice 
Not assessed 
Zalzman 
et al, 2003 
(50) 
Cloned fetal 
liver cells: 
immortalized 
with human 
telomerase 
£ind trans- 
duced 
with rat 
PDX-1 
Human and 
rat PDX-1 
(+): GK(-): 
GLUT-2 (-) 
Insulin mRNA 
(+): Insulin 
protein (+); 
No ultra- struc- 
tural examina- 
tion 
Yes 
High blood glu- 
cose concentra- 
tions reversed in 
STZ/NOD-SCID 
mice; high blood 
glucose returned 
upon graft removal 
No tumors at 
3 months after 
transplantation 
Beta-cell-specific markers: PDX-1: (a.k.a IPF-1), a regulatory gene important for 
beta-cell function; Glucokinase (GK), an enzyme that detects high levels of glu- 
cose and modulates insulin release; GLUT-2, a protein associated vvhth glucose- 
responsive insulin secretion. CK-19 is a marker for pancreatic duct cells. Insulin 
production criteria: synthesis of messenger RNA for insulin or preproinsulin; tests 
for the presence of insulin protein; and ultrastructural studies (electron micros- 
copy) to determine the presence of typical insulin secretory granules. In addition, 
the glucose-responsiveness of insulin production and release, an essential char- 
acteristic of normal beta-cell function, was assessed in a number of the studies 
described above. Both mouse models of Type-1 diabetes used mice that had a 
condition known as Severe Combined Immunodeficiency (SCID) and were treated 
with streptozotocin (STZ), a dmg that induces selective destmction of the insulin- 
producing cells. The mice in the Zalzman study were also bom with a form of 
mouse diabetes, and are called Non-Obese Diabetic (NOD) mice. 
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