Sickle Cell Disease: Pathogenesis, Diagnosis and Treatment

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 10 July 2025 | Viewed by 1417

Special Issue Editors


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Guest Editor
Department of Pediatrics, Emory University School of Medicine, Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
Interests: omics; fetal hemoglobin regulation; rheology; chronic pain

E-Mail Website
Guest Editor
Department of Pediatrics, Division of Pulmonology, Emory University School of Medicine, Atlanta, GA 30322, USA
Interests: sickle cell disease; acute chest syndrome; omics; immune system dysregulation

Special Issue Information

Dear Colleagues,

We are in an exciting era for sickle cell disease, with new drugs and gene therapies in the pipeline. With these opportunities come new questions: how do we select the best drug therapy and compare the efficacy of different gene therapy strategies? Along with these questions, there remains the question of if gene therapy is curative and even how to define a cure.

There are new devices, molecular tests, and sequencing strategies to help us answer these questions. In this Special Issue, we aim to describe the state of the science and review current applications for these new technologies. Articles describing ways to vet the safety and efficacy of gene therapy for SCD are welcome, as are articles describing omics studies or omics-based strategies that identify novel therapeutic pathways or elucidate sickle cell disease pathophysiology. Our major focus is on experimental cytology. We are also pleased to invite you to submit articles addressing new ways to assess red cell health and strategies that use existing or emerging biomarkers to identify acute complications or best second-line agents.

Dr. Vivien Sheehan
Dr. Ben Kopp
Guest Editors

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Keywords

  • sickle cell disease
  • vaso-occlusive events
  • acute chest syndrome
  • omics
  • gene therapy
  • red cell rheology
  • microfluidics

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Published Papers (1 paper)

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Research

18 pages, 3496 KiB  
Article
Heme-Oxygenase 1 Mediated Activation of Cyp3A11 Protects Against Non-Steroidal Pain Analgesics Induced Acute Liver Damage in Sickle Cell Disease Mice
by Ravi Vats, Ramakrishna Ungalara, Rikesh K. Dubey, Prithu Sundd and Tirthadipa Pradhan-Sundd
Cells 2025, 14(3), 194; https://doi.org/10.3390/cells14030194 - 28 Jan 2025
Viewed by 997
Abstract
Pain constitutes a significant comorbidity associated with sickle cell disease (SCD). Analgesics serve as the primary method for pain management; however, the long-term effects of these drugs on the liver of SCD patients remain not completely understood. Using real-time intravital imaging, we analyzed [...] Read more.
Pain constitutes a significant comorbidity associated with sickle cell disease (SCD). Analgesics serve as the primary method for pain management; however, the long-term effects of these drugs on the liver of SCD patients remain not completely understood. Using real-time intravital imaging, we analyzed the effect of non-steroidal analgesics (NSA) in the liver of control and SS (SCD) mice. Remarkably, we found completely opposing effects in the liver of control and SS mice post-NSA treatment. Whereas SS mice were able to better tolerate the NSA treatment acutely compared to their littermate controls, in the long term, these mice showed delayed resolution of liver injury and exacerbated fibrosis compared to control mice. Mechanistically, we found that SS mice were protected from cytotoxicity caused by NSA at baseline due to the significant activation of hepatic Kupffer cells, which produced heme-oxygenase 1 (HO-1). HO-1 promoted the activation of the cytoprotective enzyme Cyp3A11, which inhibited hepatic damage caused by NSA. However, in the long term, depletion of hepatic Kupffer cells led to reduced expression of HO-1, which blocked the activation of Cyp3A11, resulting in fibrosis and a delay in the resolution of liver injury and inflammation. These preclinical data provide a strong proof-of-concept for HO-1 as well as Cyp3A11 as cytoprotectors against NSA-induced liver damage in the Townes model of SCD and support further development of these compounds as potential novel therapies for end-organ damage in SCD. Full article
(This article belongs to the Special Issue Sickle Cell Disease: Pathogenesis, Diagnosis and Treatment)
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