2. Academic Validation
  3. Mesenchymal stromal cells counteract with age-related immune decline and enhance vaccine efficacy by modulating endogenous splenic marginal reticular cells in elderly models

Mesenchymal stromal cells counteract with age-related immune decline and enhance vaccine efficacy by modulating endogenous splenic marginal reticular cells in elderly models

  • Cell Mol Immunol. 2026 Feb;23(2):220-235. doi: 10.1038/s41423-025-01381-9.
Jialing Liu # 1 2 3,  Zhishan Li # 1 2 3,  Qiong Ke # 2 3 4,  Qiuli Liu # 2 3 5,  Yueming Sun 1 2 3,  Rong Yan 2 3,  Huolin Ye 5,  Yuxi Zhang 2 3,  Jie Ren 6,  Hong Chen 7,  Gang Li 2 3,  Tao Wang 2 3,  Xubo Li 8,  Yuzhe Wang 2 3,  Yuan Qiu 2 3,  Xiaoran Zhang 2 3,  Zhenxia Yao 2 3,  Rui Fang 7,  Jianqi Feng 7,  Lili Chen 9,  Weiqiang Li 10 11 12,  Xiaoyong Chen 13 14,  Andy Peng Xiang 15 16 17
Affiliations

Affiliations

  • 1 Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
  • 2 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China.
  • 3 National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 4 Department of Histoembryology and Cell Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
  • 5 Biotherapy Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • 6 Department of Medical Ultrasonication, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 7 Center for Stem Cells Translational Medicine, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, China.
  • 8 Department of Microsurgery, Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 9 Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China. [email protected].
  • 10 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China. [email protected].
  • 11 National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. [email protected].
  • 12 Department of Histoembryology and Cell Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China. [email protected].
  • 13 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China. [email protected].
  • 14 National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. [email protected].
  • 15 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China. [email protected].
  • 16 National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. [email protected].
  • 17 Department of Histoembryology and Cell Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China. [email protected].
  • # Contributed equally.
PMID: 41514017 DOI: 10.1038/s41423-025-01381-9
Abstract

Vaccination is the preferred strategy for preventing infections such as influenza in elderly individuals; however, its efficacy is often suboptimal due in part to age-related declines in immune function. In this study, we discovered that the infusion of mesenchymal stromal cells (MSCs) restored defects in the splenic stromal cell network and lymphocyte architecture in aged mice while also increasing specific antibody levels following vaccine immunization. This significantly protected aging mice from influenza Infection. Mechanistically, the delivered MSCs localized in the splenic marginal zones, where they positioned themselves near marginal reticular cells (MRCs) and stimulated MRC proliferation, partially through the action of vascular endothelial growth factor A (VEGFA). This MSC‒MRC interaction orchestrated the reconstruction of the stromal network, thereby restoring lymphocyte homeostasis and germinal center reactions. Importantly, the MSC-mediated enhancement of the vaccine response was further validated in aged cynomolgus monkeys. Collectively, our findings provide new insights into the application of MSCs in addressing age-related immune decline and highlight splenic MRCs as critical therapeutic targets.

Keywords

Aging; Marginal reticular cells (MRCs); Mesenchymal stromal cells (MSCs); Vaccine response; Vascular endothelial growth factor A (VEGFA).

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