Volatile compounds emission from teratogenic human pluripotent stem cells observed during their differentiation in vivo

Abstract

Several investigations point out that the volatile fraction of metabolites, often called volatilome, might signal the difference processes occurring in living beings, both in vitro and in vivo. These studies have been recently applied to stem cells biology, and preliminary results show that the composition of the volatilome of stem cells in vitro changes along the differentiation processes leading from pluripotency to full differentiation. The identification of pluripotent stem cells is of great importance to improve safety in regenerative medicine avoiding the formation of teratomas. In this paper, we applied gas chromatography and gas sensor array to the study of the volatilome released by mice transplanted with human induced pluripotent stem cells (hiPSCs) or embryoid bodies (EBs) derived from hiPSCs at 5 days and spontaneously differentiated cells at 27 day. Gas chromatography analysis finds that, in mice transplanted with hiPSCs, the abundance of 13 volatile compounds increases four weeks after the implant and immediately before the formation of malignant teratomas (grade 3) become observable. The same behaviour is also followed by the signals of the gas sensors. Besides this event, the gas-chromatograms and the sensors signals do not show any appreciable variation related neither among the groups of transplanted mice nor respect to a placebo population. This is the first in vivo observation of the change of volatile metabolites released by human induced pluripotent stem cells and hiPSCs-derived cells during the differentiation process. These results shed further light on the differentiation mechanisms of stem cells and suggest possible applications for diagnostic purposes for an early detection of tumor relapse after surgery.

Targeting LOX-1 Inhibits Colorectal Cancer Metastasis in an Animal Model

“…Octane-4-methyl was found at altered concentrations in the breath of patients affected by colorectal cancer (41) and lung cancer (42), while the content of nonanal in breath has been related to lung cancer (30) and ovarian cancer (43). Furthermore, both these compounds are also present among those VOCs signaling the differentiation of pluripotent stem cells (44). Here, we found that nonanal and octane-4-methyl are also released by saline injected mice, thus these compounds are likely related to normal metabolic processes and amplified by the injection of DLD-1 cells.…”

Corroles at work: a small macrocycle for great applications

“…Similar sensor arrays were used in recent years to measure the volatile compounds released by murine models to study gene knockdown in colon cancer, 184 the differentiation of pluripotent human stem cells, 185 and the progression of malaria infection. 186 A further example of the electronic nose was given by an array of four resistive porphyrins and corroles-functionalized ZnO nanoparticles assembled and tested as compared to various volatile compounds and real samples too.…”

Sensor array and gas chromatographic detection of the blood serum volatolomic signature of COVID-19

“…These sensors have been used in several metabolomics studies. For instance, they have been used in breath analysis to detect lung cancer (Gasparri et al, 2016;Di Natale et al, 2003) and tuberculosis (Zetola et al, 2017), to study in vivo and in vitro the differentiation processes of stem cells (Capuano et al, 2017;(Capuano et al, 2018) ), to study the volatile compounds of a murine model of cancer related protein knockdown (Murdocca et al, 2019), and to analyze the volatile compounds released by malaria murine models (Capuano et al, 2017) and malaria infected human erythrocytes (Capuano et al, 2019).…”