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O c t o b e r 1 5 - 1 6 , 2 0 1 8 | T o k y o , J a p a n
Obesity Congress 2018, Diabetes Congress 2018 & Vaccines Congress 2018
Note:
Page 34
Biomedical Research | ISSN: 0976-1683| Volume 29
2nd WORLD OBESITY CONGRESS
2nd WORLD VACCINES AND IMMUNOLOGY CONGRESS
&
&
DIABETES AND ENDOCRINOLOGY
International Conference on
Joint Event on
OF EXCELLENCE
IN INTERNATIONAL
MEETINGS
YEARS
Sarah Ferber, Biomed Res 2018, Volume 29 | DOI: 10.4066/biomedicalresearch-C5-012
AUTOLOGOUS CELL REPLACEMENT
THERAPY FOR DIABETIC PATIENTS BY
LIVER TRANSDIFFERENTIATION
T rans differentiation is the direct reprogramming of adult cells into alternate
cell types with different function. Liver to pancreas transdifferentiation (TD)
induced by ectopic expression of pancreatic transcription factors (pTFs) was
first described by our group both in vivo and in human liver cells in vitro. The
keynote lecture will disclose our understanding of the mechanism of liver to
pancreas TD and will describe this approach’s industrial implementation as an
autologous cell replacement therapy for diabetic patients. Our data suggest
that TD occurs in predisposed liver cells that display specific characteristics.
Moreover, TD-propensity can be extended tomost of the cells by epigeneticma-
nipulations, hence, increasing the trans differentiation efficiency. Using primary
cultures of liver derived from >20 human donors we have identified a sub-pop-
ulation of human liver cells that are persistently predisposed to undergo TD
(5-15% of the cells). Upon ectopic pTFs expression, 70% of the predisposed
liver cells produced and secreted the processed hormone in a glucose-regulat-
ed manner. Epigenetic analyses suggested that pancreatic genes’ chromatin
is more transcrpition-permissive in TD-predisposed than in recalcitrant liver
cells. TD-predisposed liver cells display a reduced level of DNA methylation
which further decreases upon the induction of reprogramming. Using epigene-
tic modifiers, we could convert TD-resistant liver cells into TD-permissive cells.
Moreover, in vitro culturing of the AIP cells in a 3D organoid manner, and their
exposure to a suitable and relevant niche, increased the transdifferentiated liv-
er cells maturation insulin production. In summary, pancreatic TD is restricted
to a specific cell population within the adult liver tissue, which harbors obligato-
ry signaling patterns and specifically permissive epigenome. The extension of
TD-propensity to most of the cells in culture/tissue, is expected to dramatically
increase this process efficiency bringing it closer to its therapeutic implemen-
tation, as an autologous cell replacement therapy for diabetic patients.
Biography
Sarah Ferber is graduated at the Technion under the
supervision of Prof. Hershko and Prof. Ciechanover
on revealing the Biology of the ubiquitin system for
protein degradation (Nobel Prize in 2004). She com-
pleted her post-Doctoral studies at Harvard Medical
School on the regulation of insulin secretion and
moved to Diabetes Cell Therapy in UTSW-Dallas TX.
She established her own research lab at Sheba Med-
ical ctr. Israel and was the first to demonstrate liver
to pancreas trans differentiation in vivo and in human
tissues in vitro for generating an autologous insulin
producing tissue. She has since published in lead-
ing journals, and her papers were cited >2700 times.
She has been serving as an editorial board member
of reputed journals and on the Israeli and the Euro-
pean boards of Gene and Cell Therapy Societies. She
serves as Orgenesis’ CSO and founder and is the in-
ventor of >10 patents on adult cells reprogramming.
Sarah Ferber
Sheba Medical Center, Israel