Transplantation of macroencapsulated tissue-engineered grafts (TEGs) is being investigated as a treatment for type 1 diabetes, but there is a critical need to measure TEG viability both in vitro and in vivo. Oxygen deficiency is the most critical issue preventing widespread implementation of TEG transplantation and delivery of supplemental oxygen (DSO) has been shown to enhance TEG survival and function in vivo. In this study, we demonstrate the first use of oxygen-17 magnetic resonance spectroscopy (17O-MRS) to measure the oxygen consumption rate (OCR) of TEGs and show that in addition to providing therapeutic benefits to TEGs, DSO with 17O2 can also enable measurements of TEG viability. Macroencapsulated TEGs containing βTC3 murine insulinoma cells were prepared with three fractional viabilities and provided with 17O2. Cellular metabolism of 17O2 into nascent mitochondrial water (H2 17O) was monitored by 17O-MRS and, from the measured data, OCR was calculated. For comparison, OCR was simultaneously measured on a separate, but equivalent sample of cells with a well-established stirred microchamber technique. OCR measured by 17O-MRS agreed well with measurements made in the stirred microchamber device. These studies confirm that 17O-MRS can quantify TEG viability noninvasively. Biotechnol. Bioeng. 2017;114: 1118–1121.
Bibliographical noteFunding Information:
This work was supported in part by the Minnesota Lions Diabetes Foundation, the Schott Family Foundation, the JDRF [grant 5-2013-141], and the NIH [grants P41 EB015894, S10 RR025031, R01 NS041262, and R01 NS070839]. The authors would like to thank all members of the Center for Magnetic Resonance Research, especially Drs. Wei Chen and Xiao-Hong Zhu. Additional thanks to Liberty Kirkeide, Dr. Thomas Suszynski, and Dr. Meri Firpo.
- bioartificial pancreas
- magnetic resonance spectroscopy
- tissue-engineered graft
- viability assessment