Monitoring and improving oxygenation of organs, cells, and tissue engineered grafts

Abstract

Oxygen is vital to the survival of many living things, and evolution has provided the human body with a complex cardiovascular system to ensure that all of the cells in the body are provided with adequate oxygen. Achieving adequate oxygen delivery remains of critical importance to the clinical management of many human diseases and has been the impetus for the development of many medical procedures and technologies. Despite much advancement in the understanding about oxygen delivery in the body, the current inability to attain life-sustaining levels of tissue oxygenation remains the major limitation for the emerging fields of cell, tissue, and organ replacement. There is a large body of research focused on developing methods to improve vascularization and oxygen supply for transplanted cells, tissues and organs, and this substantial challenge will require an interdisciplinary approach utilizing both engineering principles and a broad understanding of the physical science. The islet transplantation process can be divided into three critical steps: tissue procurement and preservation; isolation, culture and shipment; and graft transplantation and monitoring. To begin, whole organ oxygen consumption rate (WOOCR) measurements are presented for the assessment of organ viability, followed by the description of new techniques for improving the efficacy of pancreas cooling during procurement, and the use of hypothermic machine perfusion (HMP) to improve pancreas preservation. These methods can be used to qualify biological tissue products and to evaluate and improve organ procurement and preservation. Next, HMP combined with silicon-rubber-membrane (SRM) culture systems are presented as techniques to improve the quality of tissues isolated from juvenile porcine pancreata, and advanced nutrient supplementation with suspension culture systems are shown to improve β-cell expansion. Finally, 19F-MRS oximetry techniques are presented for non-invasive oxygen monitoring of tissue-engineered grafts (TEGs), and these techniques are further applied to develop, implement, and validate a novel method for oxygen delivery to an implanted tissue-engineered islet grafts.