Oxygen transporter for the hypoxic transplantation site

Abstract

Cell transplantation is a promising treatment for complementing lost function by replacing new cells with a desired function, e.g. pancreatic islet transplantation for diabetics. To prevent cell obliteration, oxygen supply is critical after transplantation, especially until the graft is sufficiently re-vascularized. To supply oxygen during this period, we developed a chemical-/electrical-free implantable oxygen transporter that delivers oxygen to the hypoxic graft site from ambient air by diffusion potential. This device is simply structured using a biocompatible silicone-based body that holds islets, connected to a tube that opens outside the body. In computational simulations, the oxygen transporter increased the oxygen level to >120 mmHg within grafts; in contrast, a control device that did not transport oxygen showed <6.5 mmHg. In vitro experiments demonstrated similar results. To test the effectiveness of the oxygen transporter in vivo, we transplanted pancreatic islets, which are susceptible to hypoxia, subcutaneously into diabetic rats. Islets transplanted using the oxygen transporter showed improved graft viability and cellular function over the control device. These results indicate that our oxygen transporter, which is safe and easily fabricated, effectively supplies oxygen locally. Such a device would be suitable for multiple clinical applications, including cell transplantations that require changing a hypoxic microenvironment into an oxygen-rich site.

Development of a novel method for measuring tissue oxygen pressure to improve the hypoxic condition in subcutaneous islet transplantation

“…Since a lack of oxygen is the most critical issue for preventing islet engraftment initially after transplantation, the delivery of exogenous oxygen may be effective for supporting the survival and function of islet grafts until revascularization occurs. In fact, unique in vivo treatment methods have been developed and tested in animal models, including localized oxygenation using a biocompatible device and bioartificial pancreas 27 , 29 and systemic oxygen inhalation 28 . To some extent, the improvement of islet engraftment in subcutaneous transplantation has been realized by these methods.…”

“…Islets were encountered with oxidative stress from isolation 22 , 23 , and after subcutaneous transplantation, islets are quite sensitive to hypoxia and require an adequate oxygen supply until the graft is revascularized 24 , 25 . Several methods have been introduced to supply oxygen to islets transplanted at the SC, to maintain transplanted cell viability and improve glucose tolerance 26 – 29 .…”

Design Considerations for Macroencapsulation Devices for Stem Cell Derived Islets for the Treatment of Type 1 Diabetes

“…Several external oxygenation technologies have been developed in the last number of years. [ 64 , 151 , 152 , 153 ] In the quest to create a bioartificial pancreas, the β ‐air device (Figure 3C ) has emerged at the forefront. This device, developed by Beta‐O 2 , comprises of: i) an alginate hydrogel containing immobilized islets, ii) an immunoisolating semi‐permeable membrane comprised of two hydrophilized PTFE membranes with a 0.45 µm pores, iii) a rubber silicone membrane that separates the encapsulated islets from the iv) oxygen reservoir.…”

Engineering Vascularized Islet Macroencapsulation Devices: An in vitro Platform to Study Oxygen Transport in Perfused Immobilized Pancreatic Beta Cell Cultures

“…However, periodic device maintenance may be required to refill the oxygen carriers. Additionally, Komatsu et al proposed an oxygen transporter device that utilizes ambient air to increase the oxygen tension in a subcutaneous transplant site ( Komatsu et al, 2018 ). This approach circumvents the need for oxygen refueling and has shown to improve encapsulated cell survival in small animal studies.…”