The Emerging Roles of the Gaseous Signaling Molecules NO, H₂S, and CO in the Regulation of Stem Cells

Abstract

Stem cell technology can be used in tissue engineering and regenerative medicine to transplant stem cells of somatic, embryonic, or induced pluripotent origin, which have tremendous potential for the treatment of currently incurable diseases. Stem cells can maintain their stemness through their self-renewal capability while promoting tissue repair and regeneration through differentiation into various target tissue cells. These two major processes of stem cell biology are precisely regulated via extracellular and intracellular signals. Gaseous signaling molecules have recently been identified to play important roles in both physiology and pathophysiology, and inhalable nitric oxide (iNO) has even been applied as a therapeutic agent. Compared with chemical formulations, these molecules have lower molecular weights and are more likely to pass through the blood–brain barrier and between cells. Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), three major gaseous signaling molecules involved in biological functions, are emerging as regulators of stem cell processes such as self-renewal, differentiation, survival, anti-apoptotic effects, proliferation, and immune rejection. Although many reviews concerning the roles of gaseous signaling molecules in different diseases or systems are available, few have focused on the roles of these molecules in the regulation of stem cells. Therefore, the aim of this paper is to systematically review the current literature on the functions and mechanisms of the gaseous signaling molecules NO, H2S, and CO in different types of stem cells and to summarize the effects of these molecules on stem cell biology and in therapy.

Near-infrared fluorescent probe for hydrogen sulfide: high-fidelity ferroptosis evaluation in vivo during stroke

“…[13][14][15] As a gaseous signaling molecule, H 2 S plays an important role in human physiological and pathological processes. 16,17 H 2 S has been dened as an important endogenous neuroprotective agent that exerts protective effects through antioxidant, anti-inammatory, and anti-apoptotic mechanisms. 18,19 A signicant amount of evidence suggests that endogenous H 2 S is produced from cysteine desulfurization catalyzed by cystathionine g lyase (CSE) or cystathionine b synthase (CBS).…”

Progress and perspective on hydrogen sulfide donors and their biomedical applications

“…10,13,83,84 Given the gaseous nature of H 2 S, the straightforward inhalation of H 2 S might be a potential approach for H 2 S delivery. Like NO and CO, whose inhalable modalities have been approved for the treatment of pulmonary hypertension in newborns and launched into clinical trials for acute respiratory distress syndrome, 85 respectively, direct H 2 S inhalation indeed elicited extensive beneficial biological effects under multiple pathological conditions without producing unpleasant byproducts. [85][86][87][88][89][90][91][92][93][94][95][96][97][98][99] Notably, the landmark paper by Roth et al demonstrated that mice inhaling the desired dosage of H 2 S via modulating its partial pressure would undergo a suspended animation-like state.…”

“…Like NO and CO, whose inhalable modalities have been approved for the treatment of pulmonary hypertension in newborns and launched into clinical trials for acute respiratory distress syndrome, 85 respectively, direct H 2 S inhalation indeed elicited extensive beneficial biological effects under multiple pathological conditions without producing unpleasant byproducts. [85][86][87][88][89][90][91][92][93][94][95][96][97][98][99] Notably, the landmark paper by Roth et al demonstrated that mice inhaling the desired dosage of H 2 S via modulating its partial pressure would undergo a suspended animation-like state. 99 This might be instrumental in ameliorating suffering of patients after surgery, organs preservation and grafting, and so on.…”

Parts-per-billion-level detection of hydrogen sulfide based on doubly resonant photoacoustic spectroscopy with line-locking

“…Apart from personal safety, H 2 S can also corrode metallic equipment, resulting in economic losses [6] , [7] . Besides, H 2 S not only is an indicator of food spoilage [8] , [9] , [10] , but also has emerged as a endogenous signal molecule with crucial pathophysiological roles in cardiovascular function [11] . Very recently, ppb-level trace H 2 S has also been used as a biomarker for the early diagnosis and therapy of lung diseases such like asthma [4] .…”