TY - JOUR
T1 - Direct Interaction Between CD34+ Hematopoietic Stem Cells and Mesenchymal Stem Cells Reciprocally Preserves Stemness
AU - Safi, Rémi
AU - Mohsen-Kanson, Tala
AU - Kouzi, Farah
AU - El-Saghir, Jamal
AU - Dermesrobian, Vera
AU - Zugasti, Inés
AU - Zibara, Kazem
AU - Menéndez, Pablo
AU - El Hajj, Hiba
AU - El-Sabban, Marwan
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/11/27
Y1 - 2024/11/27
N2 - 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.
AB - 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.
KW - acute myeloid leukemia
KW - bone marrow
KW - CD34 hematopoietic stem cells
KW - connexin 43
KW - gap junction
KW - heterocellular interaction
KW - mesenchymal stem cells
KW - microenvironment
KW - N-Cadherin
UR - http://www.scopus.com/inward/record.url?scp=85211915797&partnerID=8YFLogxK
U2 - 10.3390/cancers16233972
DO - 10.3390/cancers16233972
M3 - Article
C2 - 39682159
AN - SCOPUS:85211915797
SN - 2072-6694
VL - 16
JO - Cancers
JF - Cancers
IS - 23
M1 - 3972
ER -