Islet Cell Transplantation for Treating Type 1 Diabetes: The Bright Future of Drug Designing and Development-Juniper Publishers
Novel Approaches in Drug Designing & Development (NAPDD)
The revolutionary process of islet transplantation
for treating type 1 diabetes has been limited by the high level of graft
failure. The process of islet isolation alone has been shown to
negatively impact islet survival and function in vivo. In
addition, insults mediated by the instant blood-mediated inflammatory
reaction, hypoxia, ischemia and immune response significantly impact the
islet allograft post transplantation [1,2].
Moreover, the immune response to alloantigens and recurrence of
autoimmunity contribute to pancreatic islet transplant dysfunction [3].
Several approaches are being developed and tried to overcome this
serious problem and novel drug designing is heavily involved with
promising results and bright rewards. Some of these approaches are being
discussed briefly in this commentary.
Regenerating islet-derived protein 3 alpha; a
pancreatic secretory protein, which functions as an antimicrobial
peptide in control of inflammation and cell proliferation has been shown
to enhance islet engraftments through its cytocprotective effect and
advance the therapeutic efficacy of islet transplantation in mice [1].
Further, human mesenchymal stromal cells were shown
to have therapeutic potential in allogeneic islet transplantation for
type 1 diabetes patients and to promote islet survival and function in
vivo. Some of the mechanisms which promote islet regeneration/survival
include cyto protective and immune modulatory properties with expression
up-regulation of Annexin A1, Elastin microfibril interface 1 and
integrin-linked protein kinase [2].
Moreover, the adoptive transfer of T regulatory cells
which play a central role in maintaining immune homeostasis and
peripheral tolerance to foreign antigens in humans has the potential to
significantly improve islet graft survival. The combination of islet and
T regulatory cells co-transplantation was shown to be feasible and to
have great potential to improve islet graft survival with the
possibility to wean off or withdraw traditional immunosuppressive agents
and improve patient quality of life [3].
Additionally, red ginseng has been reported to
enhance insulin secretion-stimulating and anti-apoptotic activities in
pancreatic beta-cells improving islet cell and graft function after
isolation and transplantation, respectively. Islet pretreatment with red
ginseng showed 1.4-fold higher glucose-induced insulin secretion than
did control islets. Red ginseng pretreatment up regulated B-cell
lymphoma 2 (Bcl-2) expression and down regulated Bcl-associated X
protein (BAX), caspase-3, and inducible nitric oxide synthase (iNOS)
expression. On the other hand, glucose-induced insulin release, NO, and
apoptosis were significantly improved in red ginseng-pretreated islets
compared with cytokine-treated islets in mice [4].
Similarly, islet PEGylation was shown to protect
against nonspecific islet destruction in the early post-transplant
period of intra portal islet transplantation in rats leading to better
islet mass preservation and post-transplant outcomes [5].
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