Heme oxygenase-1: Equally important in allogeneic hematopoietic stem cell transplantation and organ transplantation?

Abstract

The intracellular enzyme heme oxygenase-1 (HO-1) is responsible for the degradation of cell-free (cf) heme. Cfheme, released upon cell damage and cell death from hemoglobin, mitochondria and myoglobin, functions as a powerful damage-associated molecular pattern (DAMP). Indeed, cfheme plays a role in a myriad of diseases characterized by (systemic) inflammation, and its rapid degradation by HO-1 is pivotal to maintain homeostasis. In the past decade, HO-1 has been extensively studied for its potential protective role in different transplantation settings, including allogeneic hematopoietic stem cell transplantation (HSCT), solid organ transplantation and pancreatic islet transplantation. These studies have shown that HO-1 can be induced by a wide range of molecules, and that induction of HO-1 has the potential to significantly reduce the incidence and severity of transplantation-related complications such as graft-versus-host disease (GvHD) and ischemia/reperfusion injury (IRI). As such, further investigation into the use of HO-1-inducing agents in human transplantation settings to facilitate the potential use of these agents in the clinic is warranted. In this review, we summarize the literature of the past 10 years on the role of HO-1 in allogeneic HSCT, solid organ transplantation (focusing on kidney and liver) and pancreatic islet transplantation. Furthermore, we provide a hypothesis about the way that HO-1 is able to provide protection against acute GvHD after allogeneic HSCT. A total of 48 research articles and 17 review articles were included in this review.

Keywords: Allogeneic hematopoietic stem cell transplantation; Cell-free heme; Heme oxygenase-1; Kidney transplantation; Liver transplantation; Pancreatic islet transplantation.