Xenogeneic Humoral Immune Responses to Human Mesenchymal Stem Cells in Mice

Jun Man Hong, Jin Hee Kim, Gwang Hoon Kim, Hyun Mu Shin, Young il Hwang

Research output: Contribution to journalArticlepeer-review


Background and Objectives: Many preclinical studies have been conducted using animal disease models to determine the effectiveness of human mesenchymal stem cells (hMSCs) for treating immune and inflammatory diseases based on the belief that hMSCs are not immunogenic across species. However, several researchers have suggested xenogeneic immune responses to hMSCs in animals, still without detailed features. This study aimed to investigate a xenogeneic humoral immune response to hMSCs in mice in detail. Methods and Results: Balb/c mice were intraperitoneally injected with adipose tissue-derived or Wharton’s jelly-derived hMSCs. Sera from these mice were titrated for each isotype. To confirm specificity of the antibodies, hMSCs were stained with the sera and subjected to a flow cytometic analysis. Spleens were immunostained for proliferating cell nuclear antigen to verify the germinal center formation. Additionally, splenocytes were subjected to a flow cytometric analysis for surface markers including GL-7, B220, CD4, CD8, CD44, and CD62L. Similar experiments were repeated in C57BL/6 mice. The results showed increased IgG1 and IgG2a titers in the sera from Balb/c mice injected with hMSCs, and the titers were much higher in the secondary sera than in the primary sera. These antibodies were specifically stained the hMSCs. Germinal centers were observed in the spleen, and flow cytometric analysis of the splenocytes showed higher frequencies of centroblasts (B220 GL7) and memory T cells (CD62L CD44) both in CD4 and CD8 subsets. Similar results were obtained for C57BL/6 mice. Conclusions: hMSCs induced a humoral immune response in mice, with characters of T cell-dependent immunity.

Original languageEnglish
Pages (from-to)291-300
Number of pages10
JournalInternational Journal of Stem Cells
Issue number3
StatePublished - Aug 2022


  • Adipose tissue-derived
  • Human mesenchymal stem cells
  • Humoral immune response
  • T cell-dependent immunity
  • Wharton’s jelly-derived
  • Xenogeneic immune response


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