The Application of Activated Stem Cells from Human Exfoliated Deciduous Teeth (SHED) in Islet Transplantation for Novel Immunosuppressive Therapy

K. Ishiyama¹, M. Kato², S. Tsunekawa², Y. Miwa¹, K. Iwasaki¹, H. Kamiya², T. Kobayashi¹

¹Division of Kidney Transplantation, Department of Surgery, Aichi Medical University, Nagakute, Japan, ²Division of Diabetes, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan

Meeting: 2022 American Transplant Congress

Abstract number: 1178

Keywords: Immunosuppression, Islets

Topic: Clinical Science » Pancreas » 65 - Pancreas and Islet: All Topics

Session Information

Session Name: Pancreas and Islet: All Topics

Session Type: Poster Abstract

Date: Sunday, June 5, 2022

Session Time: 7:00pm-8:00pm

Presentation Time: 7:00pm-8:00pm

Location: Hynes Halls C & D

*Purpose: While various attempts have been made to improve the efficiency of islet transplantation, we have been working on the analysis of the mechanism of immune cell responses of innate and acquired immunity to the graft triggered by IBMIR (Instant Blood Mediated Inflammatory Reaction) and the development of the control method. We have recently reported that NK cells are activated after islet transplantation, resulting in islet graft injury, and that simultaneous transplantation of mesenchymal stem cells (MSC), which contribute to tissue repair and healing, suppresses post-transplant immune responses and improves the outcome of islet transplantation in the mouse model.In the present study, we investigated whether the same phenomenon could be confirmed in the human immune system using Stem Cells from Human Exfoliated Deciduous teeth (SHED) derived from dental pulp and bone marrow-derived MSC.

*Methods: Immunosuppressive function of SHED and MSC against human PBMC collected from volunteers was analyzed in vivo.

*Results: We examined the phenotype of these cells stimulated with inflammatory cytokines (IL-1b,TNF-a,IFN-g) by flow cytometry, and found that SHED did not show enhanced expression of MHC class 2 upon cytokine stimulation and showed a more stable cell population compared to bone marrow-derived MSC. Furthermore, PDL1, which is not expressed in naive condition, was found to be expressed in both SHED and MSC upon cytokine stimulation. PGE2 production was also observed in bone marrow-derived MSC under cytokine stimulation, but was more markedly enhanced in SHED. In addition, inhibition of activated human PBMC with anti CD3/CD28 magnetic bead was more potent when co-cultured with SHED than that with bone marrow-derived MSC. Interestingly, this inhibitory effect was cytokine-dependent manner and involved the PDL1-mediated pathway.

*Conclusions: We confirmed the immunosuppressive effect of activated SHED as well as the possibility of an inhibitory mechanism by both humoral factors and cell contact. Simultaneous transplantation of activated SHED with islets is expected to improve islet transplant outcomes.

To cite this abstract in AMA style:

Ishiyama K, Kato M, Tsunekawa S, Miwa Y, Iwasaki K, Kamiya H, Kobayashi T. The Application of Activated Stem Cells from Human Exfoliated Deciduous Teeth (SHED) in Islet Transplantation for Novel Immunosuppressive Therapy [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/the-application-of-activated-stem-cells-from-human-exfoliated-deciduous-teeth-shed-in-islet-transplantation-for-novel-immunosuppressive-therapy/. Accessed May 9, 2025.

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