The Development of novel techniques for locoregional delivery of therapeutics to the pancreas

The pancreas has a complex anastomotic blood supply which has previously limited clinical intervention to this gland. However, with advances in microcatheter technologies, direct delivery of therapeutics to the pancreas in humans is now possible using endovascular approaches and imaging guidance.  To date, similar techniques have not been possible in small animal models.  Hence, we have developed a novel technique to delivery therapeutic agents directly to the pancreas, via its arterial blood supply, thereby minimizing non-target delivery and bypassing organs of the reticuloendothelial system.  

Pancreatic regeneration with mesenchymal stem cells

MSCs can act as a “mobile drug store” to protect and regenerate damaged cells through the release of anti-inflammatory, angiogenic, immunomodulatory, anti-fibrotic and anti-apoptotic factors. Since T1D is characterized by the destruction of β cells by autoreactive immune-mediated inflammatory responses and islet microvascular abnormalities, MSCs provide an appealing therapeutic strategy for regenerating the endocrine pancreas. We are examining the effect of delivering MSCs directly to the pancreas in diabetic animal models, via its arterial blood supply

The effects of pulsed focused ultrasound on the pancreas for mesenchymal stem cell homing

In contrast to continuous-focused ultrasound (cFUS), which deposits energy in tissues to generate extreme temperatures for ablative therapy, pulsed focused ultrasound (pFUS) utilizes short cycles of sound waves to shake tissue. This causes a transient local increase in chemoattractants (i.e. cytokines, trophic factors and cell adhesion molecules) with only very minimal temperature elevations within a normal physiological range (i.e. 1-3oC).  Up-regulation of these chemoattractants generates a “molecular zip-code”, which provides signals for MSC homing, permeability and retention.  Hence, we are examining the effects of pFUS on the pancreas.

Co-transplantation of pancreatic islets with mesenchymal stem cells

Type 1 diabetes results from the autoimmune destruction of insulin-producing ß-cells. ß-cell replacement therapies, which includes islet transplantation, represent a therapeutic alternative to the administration of exogenous insulin. However, the lack of an established islet microcirculation, hypoxia as well as immunological rejection have caused islet graft failure after islet transplantation. Mesenchymal stem cells (MSCs) possess anti-inflammatory, immune-regulatory and pro-angiogenic properties. Hence, we are investigating whether co-transplantation of MSCs with pancreatic islets will facilitate islet engraftment and survival to achieve long term glycemic control.

Construction of active bioscaffolds for islet transplantation

Although, pancreatic islet transplantation was initially hailed as a cure for T1D, this technique has failed to reach its full clinical potential.  The main reason for this failure is that 50-70% of islets are lost immediately following transplantation due to increased oxidative stress and hypoxia and the considerable time it takes islets to establish their own blood supply to ensure their survival.  We are creating biocompatible 3D structures which contain spaces to accommodate islets.  Our bioscaffolds will aim to facilitate oxygen generation and angiogenesis, both of which are essential for islet survival and function.