2. Academic Validation
  3. VLA-4 agonist promotes engraftment and immune reconstitution of allogeneic hematopoietic stem cells

VLA-4 agonist promotes engraftment and immune reconstitution of allogeneic hematopoietic stem cells

  • Blood Adv. 2026 May 12;10(9):3103-3117. doi: 10.1182/bloodadvances.2025017456.
Qiaomei He 1,  Xi Sun 1,  Lin Veronica Chen 2,  Jun Yang 1,  Ying Gao 3,  Liping Wan 1,  Yu Cai 1,  Xiao Zhou 1,  Lianghua Shen 1,  Peiyao Jiang 1,  Jiayu Liu 1,  Xiaodan Ding 1,  Lu Li 1,  Yin Tong 1,  Huiying Qiu 1,  Chongmei Huang 1,  Baoxia Dong 1,  Kun Zhou 1,  Yuqin Yang 4,  Pengran Wang 1,  Xiaozhen Liang 3,  Yan Zhang 1,  Bo O Zhou 5,  Fang Zhang 1 6,  Xianmin Song 1
Affiliations

Affiliations

  • 1 Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Ear, Nose and Throat Institute, Department of Facial Plastic and Reconstructive Surgery, Eye & ENT Hospital, Fudan University, Shanghai, China.
  • 3 Key Laboratory of Molecular Virology and Immunology, Chinese Academy of Sciences, Shanghai, China.
  • 4 Department of Laboratory Animal Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5 Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • 6 Key Laboratory of Stem Cells and Tissue Engineering (Ministry of Education), Zhongshan Medical School, Sun Yat-sen University, Guangzhou, China.
PMID: 41758999 DOI: 10.1182/bloodadvances.2025017456
Abstract

Full engraftment and early immune reconstitution of donor hematopoietic stem cells (HSCs) after allogeneic HSC transplantation (allo-HSCT) are crucial. However, effective and safe clinical modality remains lacking. Here, very late antigen-4 (VLA-4) was identified as a pivotal target for HSC engraftment, and one of its agonists was identified, which significantly promotes donor HSC engraftment and long-term hematopoietic reconstitution by enhancing its self-renewal capacity in allogeneic transplantation and serial xenotransplantation mouse models. Furthermore, the VLA-4 agonist facilitated early immune reconstitution by augmenting T-cell differentiation from HSCs, with the reconstituted immune cells exhibiting potent Antiviral effects without exacerbating acute graft-versus-host disease. Mechanistically, VLA-4 A2 activated extracellular signal-regulated kinase 1/2 phosphorylation to regulate HSC function and lymphoid progenitor differentiation, without inducing leukemogenic gene expression. These findings underscore the significant clinical translational potential of the VLA-4 agonist in promoting HSC engraftment and early cellular immune reconstitution after allo-HSCT.

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