2010-ASCB-Press-Book - page 7

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T h e A m e r i c a n s o c i e t y f o r C e l l B i o l o g y
News from
The American Society
for Cell Biology
50th Annual Meeting
Philadelphia, PA
December 11–15, 2010
Gametes to stem diabetes
EMBARGOED
FOR RELEASE
10:00 am, U.S. Eastern Time
Sunday, December 12, 2010
Contact
Ian Gallicano
Georgetown University
Medical Center
3900 Reservoir Rd., NW
Med/Dent NE205
Washington, DC 20057
202-687-0228
Author presents
Sunday, December 12, 2010
11:30 am–1:00 pm
Session: Metabolic Diseases I
Exhibit Halls A/B/C
Program: 703
Board B1113
Functional, Insulin-Secreting
Pancreatic Endoderm Derived
from Human Spermatogonial
Stem Cells
Anirudh Saraswathula
1
,
Shenglin Chen
2
, Asif Zakaria
2
,
and G. Ian Gallicano
2
1 Biotechnology and Life Sci-
ences Laboratory, Science
and Technology Division,
Thomas Jefferson High School
for Science and Technology,
Alexandria, VA
2 Department of Biochemistry
and Molecular and Cellular
Biology, Georgetown University
Medical Center, Washington,
DC
A grow-your-own-insulin transplant
strategy for men with type I
diabetes would turn sperm cell
precursors into pancreatic islets
D
espite the rising tide of diabetes
patients and dire predictions of
worse to come, diabetes treat-
ment has advanced little for decades
beyond blood testing and insulin replace-
ment. The only radically new approach to
type I diabetes in recent years has been
the Edmonton Protocol, named after the
Canadian city where the technique was
standardized, for transplanting insulin-
producing
b
-islet cells from deceased
donors into the pancreas of diabetic
patients who can no longer survive on
insulin injections. But a woeful shortage
of suitable donations and all the graft-
versus-host and immune suppression
problems associated with transplants
have hampered islet transplants.
Basic research presses ahead on po-
tential embryonic stem cell therapies for
type I diabetes, but a research team led by
Ian Gallicano at Georgetown University
Medical Center inWashington, DC, is ex-
ploring a more readily available source of
stem cells suitable for transformation into
transplantable islet cells—human sper-
matogonial stem cells (SSCs). These cells
are the earliest precursors of sperm cells
and could be taken from patients them-
selves and modified to secrete insulin.
Gallicano and colleagues report success
in the first stage of their plan—engineer-
ing insulin-secreting endodermal cells by
using human SSCs directly isolated from
human testicular tissue.
Gallicano’s
b
-islet–like cells were
bioengineered from germ-derived pluri-
potent stem (gPS) cells produced from
the SSCs. The engineered
b
-islet cells
secrete insulin and exhibit many of the
markers characteristic of normal islet
cells, including C-peptide (proinsulin)
production and the expression of PDX1, a
transcription factor involved in pancreatic
development. They also behave much like
somatic
b
-islet cells, says Gallicano. Most
significantly, human-derived islet cells
grafted into diabetic mice (who lacked
a transplant-rejecting immune system)
decreased blood-glucose levels of the
mice, demonstrating the ability to counter
diabetic hyperglycemia.
But Gallicano intends to treat men,
not mice. He envisions harvesting SSCs
from a diabetic male patient, transform-
ing them into gPS cells, and transplanting
them back into the original donor, where
they will differentiate into the missing
b
-
islet cells. This approach, says Gallicano,
avoids the entire donor-versus-host issue
since the donor and host are the same
man. “This method of obtaining
b
-islet–
like cells solves the problem of immune
rejection in male diabetes patients,” he
explains, “as treatment based on this re-
search would be ‘autologous’; that is, the
cells come from the patient and would be
recognized as ‘self.’”
Nor is this approach using sperm cell
precursors strictly “male-centric.” Gallica-
no contends that the fundamental aspects
of transforming male gametes into pluri-
potent stem cells could easily be applied
to the female counterpart, oocytes.
Confocal microscopy of pancreatic-like cells derived from human spermatogonial stem cells (SSCs)
shows production of insulin. Inset in (A) shows the differential interference contrast image of A and B.
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