Adipose-Derived Mesenchymal Stem Cell Facilitate Hematopoietic Stem Cell Proliferation via the Jagged-1/Notch-1/Hes Signaling Pathway

Hongbo Wang; Xiaojuan Bi; Rongyao Zhang; Hailong Yuan; Jianli Xu; Kaile Zhang; Songqing Qi; Xue Zhang; Ming Jiang

doi:10.1155/2023/1068405

Adipose-Derived Mesenchymal Stem Cell Facilitate Hematopoietic Stem Cell Proliferation via the Jagged-1/Notch-1/Hes Signaling Pathway

Stem Cells Int. 2023 Nov 9:2023:1068405. doi: 10.1155/2023/1068405. eCollection 2023.

Authors

Hongbo Wang^{1

2}, Xiaojuan Bi³, Rongyao Zhang^{1

2}, Hailong Yuan^{1

2}, Jianli Xu^{1

2}, Kaile Zhang^{1

2}, Songqing Qi^{1

2}, Xue Zhang^{1

2}, Ming Jiang^{1

2}

Affiliations

¹ Hematology Center, The First Affiliated Hospital of Xinjiang Medical University (Xinjiang Uygur Autonomous Region Institute of Hematology), Urumqi 830054, China.
² Stem Cell Research Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
³ The State Key Laboratory of Pathogenesis and Prevention of Central Asian High Incidence Diseases, Institute of Clinical Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.

Abstract

Background: Poor graft function (PGF) is a life-threatening complication following hematopoietic stem cell transplantation (HSCT). Current therapies, such as CD34⁺ cell infusion, have shown limited effectiveness. Conversely, mesenchymal stem cells (MSCs) show potential in addressing PGF. Adipose-derived mesenchymal stem cells (ADSCs) effectively support long-term hematopoietic stem cell proliferation. Therefore, this study aimed to investigate the mechanisms underlying the long-term hematopoietic support provided by ADSCs.

Methods: ADSCs were isolated from mice and subsequently identified. In vitro experiments involved coculturing ADSCs as feeders with Lin-Sca-1⁺c-kit⁺ (LSK) cells from mice for 2 and 5 weeks. The number of LSK cells was quantified after coculture. Scanning electron microscopy was utilized to observe the interaction between ADSCs and LSK cells. Hes-1 expression was assessed using western blot and real-time quantitative PCR. An γ-secretase inhibitor (GSI) was used to confirm the involvement of the Jagged-1/Notch-1/Hes-1 pathway in LSK cell expansion. Additionally, Jagged-1 was knocked down in ADSCs to demonstrate its significance in ADSC-mediated hematopoietic support. In vivo experiments were conducted to study the hematopoietic support provided by ADSCs through the infusion of LSK, LSK + fibroblasts, and LSK + ADSCs, respectively. Mouse survival, platelet count, leukocyte count, and hemoglobin levels were monitored.

Results: ADSCs showed high-Jagged-1 expression and promoted LSK cell proliferation. There was a direct interaction between ADSCs and LSK cells. After coculture, Hes-1 expression increased in LSK cells. Moreover, GSI-reduced LSK cell proliferation and Hes-1 expression. Knockdown of Jagged-1 attenuated ADSCs-mediated promotion of LSK cell proliferation. Furthermore, ADSCs facilitated hematopoietic recovery and promoted the survival of NOD/SCID mice.

Conclusion: The hematopoietic support provided by ADSCs both in vivo and in vitro may be mediated, at least in part, through the Jagged-1/Notch-1 signaling pathway. These findings provide valuable insights into the mechanisms underlying ADSCs-mediated hematopoietic support and may have implications for improving the treatment of PGF following HSCT.