A mouse model of vascularized heterotopic spleen transplantation for studying spleen cell biology and transplant immunity

Jiao Jing Wang, Longhui Qiu, Ramiro Fernandez, Xin Yi Yeap, Charlie Xiaoying Lin, Zheng Jenny Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

The spleen is a unique lymphoid organ that plays a critical role in the homeostasis of the immune and hematopoietic systems. Patients that have undergone splenectomy regardless of precipitating causes are prone to develop an overwhelming post-splenectomy infection and experience increased risks of deep venous thrombosis and malignancies. Recently, epidemiological studies indicated that splenectomy might be associated with the occurrence of cardiovascular diseases, suggesting that physiological functions of the spleen have not yet been fully recognized. Here, we introduce a mouse model of vascularized heterotopic spleen transplantation, which not only can be utilized to study the function and behavioral activity of splenic immune cell subsets in different biologic processes, but also can be a powerful tool to test the therapeutic potential of spleen transplantation in certain diseases. The main surgical steps of this model include donor spleen harvest, the removal of recipient native spleen, and spleen graft revascularization. Using congenic mouse strains (e.g., mice with CD45.1/CD45.2 backgrounds), we observed that after syngeneic transplantation, both donor-derived splenic lymphocytes and myeloid cells migrated out of the graft as early as post-operative day 1, concomitant with the influx of multiple types of recipient cells, thus generating a unique chimera. Despite relatively challenging techniques, this procedure can be performed with >90% success rate. This model allows tracking the fate, longevity, and function of splenocytes during steady state and in a disease setting following a spleen transplantation, thereby offering a great opportunity to discover the distinct role for spleen-derived immune cells in different disease processes.

Original languageEnglish (US)
Article numbere59616
JournalJournal of Visualized Experiments
Volume2019
Issue number148
DOIs
StatePublished - Jun 2019

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Cytology
Heterotopic Transplantation
Transplantation (surgical)
Transplants
Cell Biology
Immunity
Spleen
Grafts
Splenectomy
Lymphocytes
Set theory
Transplantation
Isogeneic Transplantation
Tissue Donors
Congenic Mice
Anatomic Models
Hematopoietic System
Myeloid Cells
Venous Thrombosis
Epidemiologic Studies

Keywords

  • Cell biology
  • Issue 148
  • Medicine
  • Microsurgery
  • Model
  • Mouse
  • Spleen
  • Transplantation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Wang, Jiao Jing ; Qiu, Longhui ; Fernandez, Ramiro ; Yeap, Xin Yi ; Lin, Charlie Xiaoying ; Zhang, Zheng Jenny. / A mouse model of vascularized heterotopic spleen transplantation for studying spleen cell biology and transplant immunity. In: Journal of Visualized Experiments. 2019 ; Vol. 2019, No. 148.
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abstract = "The spleen is a unique lymphoid organ that plays a critical role in the homeostasis of the immune and hematopoietic systems. Patients that have undergone splenectomy regardless of precipitating causes are prone to develop an overwhelming post-splenectomy infection and experience increased risks of deep venous thrombosis and malignancies. Recently, epidemiological studies indicated that splenectomy might be associated with the occurrence of cardiovascular diseases, suggesting that physiological functions of the spleen have not yet been fully recognized. Here, we introduce a mouse model of vascularized heterotopic spleen transplantation, which not only can be utilized to study the function and behavioral activity of splenic immune cell subsets in different biologic processes, but also can be a powerful tool to test the therapeutic potential of spleen transplantation in certain diseases. The main surgical steps of this model include donor spleen harvest, the removal of recipient native spleen, and spleen graft revascularization. Using congenic mouse strains (e.g., mice with CD45.1/CD45.2 backgrounds), we observed that after syngeneic transplantation, both donor-derived splenic lymphocytes and myeloid cells migrated out of the graft as early as post-operative day 1, concomitant with the influx of multiple types of recipient cells, thus generating a unique chimera. Despite relatively challenging techniques, this procedure can be performed with >90{\%} success rate. This model allows tracking the fate, longevity, and function of splenocytes during steady state and in a disease setting following a spleen transplantation, thereby offering a great opportunity to discover the distinct role for spleen-derived immune cells in different disease processes.",
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A mouse model of vascularized heterotopic spleen transplantation for studying spleen cell biology and transplant immunity. / Wang, Jiao Jing; Qiu, Longhui; Fernandez, Ramiro; Yeap, Xin Yi; Lin, Charlie Xiaoying; Zhang, Zheng Jenny.

In: Journal of Visualized Experiments, Vol. 2019, No. 148, e59616, 06.2019.

Research output: Contribution to journalArticle

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AU - Wang, Jiao Jing

AU - Qiu, Longhui

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AU - Lin, Charlie Xiaoying

AU - Zhang, Zheng Jenny

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