Murine bone marrow mesenchymal stromal cells have reduced hematopoietic maintenance ability in sickle cell disease

Alice Tang, Ana Nicolle Strat, Mahmudur Rahman, Helen Zhang, Weili Bao, Yunfeng Liu, David Shi, Xiuli An, Deepa Manwani, Patricia Shi, Karina Yazdanbakhsh, Avital Mendelson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Sickle cell disease (SCD) is characterized by hemolytic anemia, which can trigger oxidative stress, inflammation, and tissue injury that contribute to disease complications. Bone marrow mesenchymal stromal cells (MSCs) tightly regulate hematopoietic stem cell (HSC) homeostasis in health and disease, but their functionality in SCD remains unclear. We identified for the first time that murine SCD MSCs have altered gene signatures, reduced stem cell properties, and increased oxidative stress, due in part to hemolysis. Murine SCD MSCs had lower HSC maintenance ability in vitro and in vivo, as manifested by increased HSC mobilization and decreased HSC engraftment after transplant. Activation of Toll-like receptor-4 through p65 in MSCs further contributed to MSC dysfunction. Transfusions led to an improved MSC and HSC oxidative state in SCD mice. Improving the regulation between MSCs and HSCs has vital implications for enhancing clinical HSC transplantation and gene therapy outcomes and for identification of new molecular targets for alleviating SCD complications.

Original languageEnglish (US)
Pages (from-to)2570-2582
Number of pages13
JournalBlood
Volume138
Issue number24
DOIs
StatePublished - Dec 16 2021

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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