The availability of donors for transplantation
of human b-cells as a form of treatment for type II diabetes
is limited. Introduction of differentiated human bone
marrow-derived mesenchymal stem cells (MSCs) would
allow transplantation of an autologous source of b-cells.
This would alleviate the limitations of availability and/or
allogenic rejection following pancreatic or islet
transplantation.
Materials and methods Bone marrow cells were
obtained from three adult type II diabetic volunteers and
three nondiabetic donors. After 3 days in culture, adherent
MSCs were expanded for two passages. At passage 3,
differentiation was carried out in a three-staged procedure.
Cells were cultured in a glucose-rich medium containing
activation and growth factors including B27, betacellulin,
activin A, and nicotinamde. These cells were evaluated for
endocrine characteristics by flow cytometry and
morphology. Differentiated cells were transplanted under
the kidney capsule of diabetic nude mice and their diabetic
status was tested by oral glucose tolerance tests.
Results Following differentiation, cells expressed the
hormones insulin, glucagon, and somatostatin. No
differences in cell characteristics were noted between
diabetic and nondiabetic donors. Hormones were
detectable by immunomicroscopy in some cells.
Transplantation into diabetic mice resulted in secretion of
human insulin, near-normalization of glucose levels, and
improvements in glucose intolerance. When the MSCbearing
kidneys were removed, rapid return of diabetic
state was noted. Histology of the removed kidneys
identified insulin-positive cells in the graft.
Conclusion Human MSCs from diabetic and nondiabetic
donors can be differentiated in vitro to form insulinproducing
cells that can restore normoglycemia in diabetic
mice. This source of material for autologous
transplantation offers new opportunities for the treatment
of diabetes. Egypt J Pathol 00:000–000 c 2016 Egyptian
Journal of Pathology. |
