1. β3-Adrenoreceptors as ROS Balancer in Hematopoietic Stem Cell Transplantation.
- Author
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Pasha A, Calvani M, and Favre C
- Subjects
- Adrenergic beta-3 Receptor Antagonists therapeutic use, Animals, Bone Marrow drug effects, Bone Marrow metabolism, Bone Marrow pathology, Gene Expression Regulation, Hematologic Diseases drug therapy, Hematologic Diseases immunology, Hematologic Diseases pathology, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells drug effects, Hematopoietic Stem Cells immunology, Humans, Immune System Diseases drug therapy, Immune System Diseases immunology, Immune System Diseases pathology, Metabolism, Inborn Errors drug therapy, Metabolism, Inborn Errors genetics, Metabolism, Inborn Errors immunology, Metabolism, Inborn Errors pathology, Neoplasms drug therapy, Neoplasms immunology, Neoplasms pathology, Oxidative Stress, Propanolamines therapeutic use, Reactive Oxygen Species immunology, Receptors, Adrenergic, beta-3 immunology, Transplantation, Autologous, Transplantation, Homologous, Hematologic Diseases genetics, Hematopoietic Stem Cells metabolism, Immune System Diseases genetics, Neoplasms genetics, Reactive Oxygen Species metabolism, Receptors, Adrenergic, beta-3 genetics
- Abstract
In the last decades, the therapeutic potential of hematopoietic stem cell transplantation (HSCT) has acquired a primary role in the management of a broad spectrum of diseases including cancer, hematologic conditions, immune system dysregulations, and inborn errors of metabolism. The different types of HSCT, autologous and allogeneic, include risks of severe complications including acute and chronic graft-versus-host disease (GvHD) complications, hepatic veno-occlusive disease, lung injury, and infections. Despite being a dangerous procedure, it improved patient survival. Hence, its use was extended to treat autoimmune diseases, metabolic disorders, malignant infantile disorders, and hereditary skeletal dysplasia. HSCT is performed to restore or treat various congenital conditions in which immunologic functions are compromised, for instance, by chemo- and radiotherapy, and involves the administration of hematopoietic stem cells (HSCs) in patients with depleted or dysfunctional bone marrow (BM). Since HSCs biology is tightly regulated by oxidative stress (OS), the control of reactive oxygen species (ROS) levels is important to maintain their self-renewal capacity. In quiescent HSCs, low ROS levels are essential for stemness maintenance; however, physiological ROS levels promote HSC proliferation and differentiation. High ROS levels are mainly involved in short-term repopulation, whereas low ROS levels are associated with long-term repopulating ability. In this review, we aim summarize the current state of knowledge about the role of β3-adrenoreceptors (β3-ARs) in regulating HSCs redox homeostasis. β3-ARs play a major role in regulating stromal cell differentiation, and the antagonist SR59230A promotes differentiation of different progenitor cells in hematopoietic tumors, suggesting that β3-ARs agonism and antagonism could be exploited for clinical benefit.
- Published
- 2021
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