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Morphologic Analysis of Beta Cell Growth in Transplant Models

Thursday, 8 December, 2005 - 16:00
Campus: Brussels Health Campus
Faculty: Medicine and Pharmacy
auditorium R. Vanden Driessche
Marika Bogdani
phd defence

Insulin-dependent diabetes develops following a
massive and selective death of pancreatic beta cells.
Transplantation of insulin-producing tissue is since long
considered as a treatment of choice for diabetes.
Clinical success has been achieved with beta cell
allografts but can not be extrapolated to larger
numbers since there is a serious shortage in organ

The capacity of fetal and neonatal pancreases to
generate new beta cells harbors the property of
producing large numbers of beta cells for
transplantation. The mechanisms underlying growth of
the beta cell mass may involve formation of new beta
cells from as yet unidentified precursor cells and/or
from proliferating beta cells. The relative contribution
of both pathways is unknown. It is also unclear whether
one or both operate in all stages of life and whether
they can be activated in grafts.

The Diabetes Research Center-VUB undertakes studies
to identify preparations and conditions in which new
beta cells are formed. The work presented in this thesis
has been conducted within the framework of this
program. Its first part investigates whether beta cells
can be formed from postnatal human pancreatic nonendocrine
cell preparations. The second part
examines beta cell formation from prenatal porcine
pancreatic endocrine cell preparations. A
morphometric method was developed to quantify
and monitor changes in size and number of beta cells
implanted as grafts, and thus of the beta mass in
transplant recipients. Human duct cell preparations
from donors under age 10 years were found to
generate insulin-positive cells following transplantation.
This property was not identified in duct cell
preparations obtained from older donors. We also
demonstrate that immature beta cells can achieve a
sustained renewal and growth of the beta cell mass.
Implants of pure fetal porcine endocrine cells
preparations grow in size mainly as a result of an
increase in beta cell number; they mature functionally,
so that they prevent development of diabetes without
a decline in their insulin reserves. The presently used
preparations can thus serve further work on the
regulation of beta cell proliferation and differentiation,
and on development of new sources of beta cells.