2010-ASCB-Press-Book - page 7

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
10:00 am, U.S. Eastern Time
Sunday, December 12, 2010
Ian Gallicano
Georgetown University
Medical Center
3900 Reservoir Rd., NW
Med/Dent NE205
Washington, DC 20057
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
Shenglin Chen
, Asif Zakaria
and G. Ian Gallicano
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,
A grow-your-own-insulin transplant
strategy for men with type I
diabetes would turn sperm cell
precursors into pancreatic islets
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-
-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.
-islet–like cells were
bioengineered from germ-derived pluri-
potent stem (gPS) cells produced from
the SSCs. The engineered
-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
-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
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
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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