Adipose tissue-derived mesenchymal stem cells ameliorate bone marrow aplasia related with graft-versus-host disease in experimental murine models

Yukiko Nishi; Akikazu Murakami; Yuko Murayama; Narutoshi Tsukahara; Shiki Okamoto; Sawako Nakachi; Kazuho Morichika; Keita Tamaki; Hirofumi Noguchi; Masayuki Matsushita; Ken-Nosuke Karube; Takuya Fukushima; Satoko Morishima; Hidehiro Kishimoto; Hiroaki Masuzaki

doi:10.1016/j.trim.2019.03.004

Adipose tissue-derived mesenchymal stem cells ameliorate bone marrow aplasia related with graft-versus-host disease in experimental murine models

Transpl Immunol. 2019 Aug:55:101205. doi: 10.1016/j.trim.2019.03.004. Epub 2019 Apr 1.

Authors

Affiliations

¹ Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
² Department of Parasitology & Immunopathoetiology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
³ Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
⁴ Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
⁵ Department of Pathology and Cell Biology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
⁶ Laboratory of Hematoimmunology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
⁷ Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. Electronic address: hiroaki@med.u-ryukyu.ac.jp.

PMID: 30946889
DOI: 10.1016/j.trim.2019.03.004

Abstract

Graft-versus-host disease (GVHD) constitutes the most frequent complications after the allogeneic hematopoietic stem cell transplantation for a variety of hematological malignancies. In the present study, we explored the prophylactic potential of adipose tissue-derived mesenchymal stem cells (AD-MSCs) in controlling GVHD in murine models with a special focus on bone marrow aplasia related with acute GVHD. The CB6F1 mice were induced GVHD by the injection intravenously of C57BL/6 (B6-Ly-5.1) splenocytes without conditioning irradiation or chemotherapy. AD-MSCs from C3H mice were injected intravenously via tail veins. GVHD was assessed using flowcytometry analysis of peripheral blood cells and histopathologic analysis of target organs. Histopathological analyses revealed that AD-MSCs markedly suppressed the infiltration of lymphocytes into liver as well as the aplasia in bone marrow. This study is the first to clarify the effectiveness of AD-MSCs against bone marrow aplasia in GVHD, supporting a rationale of AD-MSCs for ameliorating bone marrow suppression and infectivity after allo-HSCT in human clinics.

Keywords: Adipose tissue derived mesenchymal stem cells; Aplasia; Bone marrow; Graft-versus-host disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue
Allografts
Animals
Bone Marrow Diseases* / etiology
Bone Marrow Diseases* / immunology
Bone Marrow Diseases* / pathology
Bone Marrow Diseases* / therapy
Disease Models, Animal
Graft vs Host Disease* / etiology
Graft vs Host Disease* / immunology
Graft vs Host Disease* / pathology
Graft vs Host Disease* / therapy
Hematopoietic Stem Cell Transplantation*
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells / immunology*
Mesenchymal Stem Cells / pathology
Mice