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J Nutr Hum Health 2017 Volume 1 Issue 2
Page 24
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July 24-26, 2017 | Vancouver, Canada
International conference on
DIABETES, NUTRITION, METABOLISM & MEDICARE
allied
academies
T
ransplantation of stem cells-derived beta cells has been
a target of diabetes research for many years, but has yet
to mature into a therapeutic option. We showed previously
that proliferating human islet-derived de-differentiated cells
(DIDs) exhibit many characteristics of mesenchymal stem
cells (MSC). Dispersed DIDs, induced by serum deprivation
to undergo mesenchymal-to-epithelial transition, aggregate
into epithelial cell clusters (ECCs). ECCs implanted under
kidney capsules of SKID mice tend to differentiate into
β-cell colony. Albeit in a large proportion of mice implanted
cells de-differentiate back to stem-like phenotype. As ECCs
disperse and undergo epithelial-to-mesenchymal transition
by re-addition of sera, we postulated that the differentiation
failure in vivo may have been due to an agent in the host
serum. We found that PDGF-BB alone mimics serum-induced
ECCs’ dispersal accompanied by accumulation of cytoplasmic
b-catenin and a decrease in the levels of insulin and glucagon
mRNAs. Moreover, PDGF-BB-induced dispersal of ECCs was a
more general phenomenon that occurred with bone marrow
MSC and dermal fibroblasts (DFs). In DIDs, BM-MSC, and
DFs, PDGF decreased the levels of DKK1 mRNA, suggesting
involvement of the Wnt signaling pathway. PDGF-BB
stimulated a significant increase in S473 phosphorylation of
Akt and the PI3K specific inhibitor (PIP828) partially inhibited
PDGF-BB-induced ECC dispersal. Lastly, the PDGF-receptor
(PDGF-R) antagonist JNJ-10198409 inhibited both PDGF-BB
and serum-induced ECC dispersal. Epidermal growth factor
(EGF), which shares most of the PDGF signaling pathway,
did not induce dispersal and only weakly stimulated Akt
phosphorylation. Hence, PDGF-BB mediated serum-induced
DIDs dispersal correlated with the activation of the PI3K-Akt
pathway. In conclusion, although we may manipulate cells to
change their physiology, the ultimate result depends onmany
uncontrolled and/or unknown factors. Our understandings
of the complexity of inter and an intracellular interaction
in vitro
and in vivo is still too sketchy to allow prediction of
therapeutic outcomes.
Biography
Yoram Oron is currently a Professor Emeritus at the Department of Physiology and
Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Israel. He received his
BSc in Chemistry and his MSc and PhD in Biochemistry from the Hebrew University
in Jerusalem. He further trained in diabetes research at the University of Virginia in
the laboratory of Professor Joseph Larner and continued to study signal transduction
pathways at Tel Aviv University, utilizing mainly the Xenopus oocyte system and elec-
trophysiology and microscopic imaging techniques as read-outs. In the last 12 years he
has changed the focus of his research to studying the biology of diabetes and pancre-
atic adenocarcinoma. In the past he served as Department Chair and as a Head of the
Office of International Academic Relations at Tel Aviv University. He has authored and
co-authored more than 110 peer-reviewed publications in quality journals, including
Nature, Science, PNAS, and J Physiol.
medfair@post.tau.ac.ilYoram Oron
Tel Aviv University, Israel
Subtle traps: Lessons from transplantation of pancreatic beta-precursor MSC