Impaired bone marrow microenvironment and stem cells in transfusion-dependent beta-thalassemia.

Xiaoya Zhou, Li Huang, Jieying Wu, Yuhua Qu, Hua Jiang, Jinqiu Zhang, SiYuan Qiu, Can Liao, Xiang Xu, Jianchuan Xia, Qizhou Lian

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2022;146():112548

PMID: 34923340

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Abstract

Beta-thalassemia (BT) is a hereditary disease caused by abnormal hemoglobin synthesis with consequent ineffective erythropoiesis. Patients with thalassemia major are dependent on long-term blood transfusions with associated long-term complications such as iron overload (IO). This excess iron can result in tissue damage, impaired organ function, and increased morbidity. Growing evidence has demonstrated that IO contributes to impairment of the bone marrow (BM) microenvironment that largely impacts the function of BM mesenchymal stem cells, hematopoietic stem cells, and endothelial cells. In this article, we review recent progress in the understanding of iron metabolism and the perniciousness induced by IO. We highlight the importance of understanding the cross-talk between BM stem cells and the BM microenvironment, particularly the pathological effect of IO on BM stem cells and BT-associated complications. We also provide an update on recent novel therapies to cure transfusion-dependent beta-thalassemia and iron overload-induced complications for their future clinical application.

Address: Cord Blood Bank, Guangzhou Institute of Eugenics and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510000, China.; Department of Haematology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510000, China.; Department of Surgery, The University of Hong Kong Shenzhen Hospital, Shenzhen 518053, China.; Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing 400042, China.; Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.; Cord Blood Bank, Guangzhou Institute of Eugenics and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510000, China; Department of Surgery, The University of Hong Kong Shenzhen Hospital, Shenzhen 518053, China; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong; HKUMed Laboratory of Cellular Therapeutics, The University of Hong Kong, Hong Kong. Electronic address: [email protected].

DOI: 10.1016/j.biopha.2021.112548

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MeSH Terms: Blood Transfusion, Bone Marrow, Bone Marrow Cells, Erythroid Cells, Hematopoietic Stem Cells, Humans, Iron, Iron Chelating Agents, Iron Overload, Mesenchymal Stem Cells, Stem Cell Niche, beta-Thalassemia