In Vivo Noninvasive Monitoring of Dissolved Oxygen Concentration Within an Implanted Tissue-Engineered Pancreatic Construct

Abstract

The function of an implanted tissue-engineered pancreatic construct is influenced by many in vivo factors; however, assessing its function is based primarily on end physiologic effects. As oxygen significantly affects cell function, we established a dual perfluorocarbon method that utilizes 19 F nuclear magnetic resonance spectroscopy, with perfluorocarbons as oxygen concentration markers, to noninvasively monitor dissolved oxygen concentration (DO) in bTC-tet cell-containing alginate beads and at the implantation milieu. Beads were implanted in the peritoneal cavity of normal and streptozotocin-induced diabetic mice. Using this method, the feasibility of acquiring real-time in vivo DO measurements was demonstrated. Results showed that the mouse peritoneal environment is hypoxic and the DO is further reduced when bTC-tet cell constructs were implanted. The DO within cell-containing beads decreased considerably over time and could be correlated with the relative changes in the number of viable encapsulated cells. The reduction of construct DO due to the metabolic activity of the bTC-tet cells was also compatible with the implant therapeutic function, as observed in the reversal of hyperglycemia in diabetic mice. The importance of these findings in assessing implant functionality and host animal physiology is discussed.

Development and Validation of Noninvasive Magnetic Resonance Relaxometry for the In Vivo Assessment of Tissue-Engineered Graft Oxygenation

“…Eleven publications reporting information on PFCE R 1 oxygen sensitivity were identified. 28,[30][31][32][33][34][35][36][38][39][40] One was excluded for inconsistent reporting of data 38 and another was excluded for results that differed from other reported data by several standard deviations, 40 leaving eleven reported calibrations 28,[30][31][32][33][34][35][36]39 that were combined with our data for analysis. Oxygen sensitivity decreased (-6.39 · 10 -5 mmHg -1…”

“…PFC-loaded alginate beads implanted into the rodent kidney capsule, peritoneal cavity, and quadriceps femoris muscle reveal a hypoxic environment unconducive to islet survival. 38,[42][43][44] Macroencapsulated cell systems, however, are often implanted into the subcutaneous space 2 and these studies, limited to microencapsulation, did not examine the oxygen availability of this site.…”

Therapeutic Effects of a Non–β Cell Bioartificial Pancreas in Diabetic Mice

“…Estimates of transplant volumes to normalize glycemia were based on reported insulin secretion from microencapsulated βTC-tet cells that restored normoglycemia in STZ-induced diabetic mice (13). EINS data from Figure 1C indicated that 7.5 mL microcapsules would be sufficient to control glycemia, but due to space restrictions, 3 mL (corresponding to 9x10 7 EINS cells) was the maximum volume attempted for transplant in mice.…”

Analysis of acquired resistance to metronomic oral topotecan chemotherapy plus pazopanib after prolonged preclinical potent responsiveness in advanced ovarian cancer

“…Within the context of the model of ovarian cancer used in our studies, it has been previously noted that the intraperitoneal cavity in mice is hypoxic [38]. As such, progression of disease in this environment may be strongly influenced by the expression or inhibition of HIF-1 alpha and/or HIF-2α.…”