Direct Interaction Between CD34+ Hematopoietic Stem Cells and Mesenchymal Stem Cells Reciprocally Preserves Stemness

Rémi Safi, Tala Mohsen-Kanson, Farah Kouzi, Jamal El-Saghir, Vera Dermesrobian, Inés Zugasti, Kazem Zibara, Pablo Menéndez, Hiba El Hajj, Marwan El-Sabban*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background/Objectives: A specialized microenvironment in the bone marrow, composed of stromal cells including mesenchymal stem cells (MSCs), supports hematopoietic stem cell (HSC) self-renewal, and differentiation bands play an important role in leukemia development and progression. The reciprocal direct interaction between MSCs and CD34+ HSCs under physiological and pathological conditions is yet to be fully characterized. Methods: Here, we established a direct co-culture model between MSCs and CD34+ HSCs or MSCs and acute myeloid leukemia cells (THP-1, Molm-13, and primary cells from patients) to study heterocellular communication. Results: Following MSCs-CD34+ HSCs co-culture, the expression of adhesion markers N-Cadherin and connexin 43 increased in both cell types, forming gap junction channels. Moreover, the clonogenic potential of CD34+ HSCs was increased. However, direct contact of acute myeloid leukemia cells with MSCs reduced the expression levels of connexin 43 and N-Cadherin in MSCs. The impairment in gap junction formation may potentially be due to a defect in the acute myeloid leukemia-derived MSCs. Interestingly, CD34+ HSCs and acute myeloid leukemia cell lines attenuated MSC osteoblastic differentiation upon prolonged direct cell–cell contact. Conclusions: In conclusion, under physiological conditions, connexin 43 and N-Cadherin interaction preserves stemness of both CD34+ HSCs and MSCs, a process that is compromised in acute myeloid leukemia, pointing to the possible role of gap junctions in modulating stemness.

Original languageEnglish
Article number3972
JournalCancers
Volume16
Issue number23
DOIs
Publication statusPublished - 27 Nov 2024
Externally publishedYes

Keywords

  • acute myeloid leukemia
  • bone marrow
  • CD34 hematopoietic stem cells
  • connexin 43
  • gap junction
  • heterocellular interaction
  • mesenchymal stem cells
  • microenvironment
  • N-Cadherin

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