TY - JOUR
T1 - Protection of liver sinusoids by intravenous administration of human Muse cells in a rat extra-small partial liver transplantation model
AU - Shono, Yoshihiro
AU - Kushida, Yoshihiro
AU - Wakao, Shohei
AU - Kuroda, Yasumasa
AU - Unno, Michiaki
AU - Kamei, Takashi
AU - Miyagi, Shigehito
AU - Dezawa, Mari
N1 - Funding Information:
This study was supported by the Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (17K10504); and collaborative research development with Life Science Institute, Inc. The authors thank Chikako Sato (Department of Surgery), Yasuko Furukawa (Department of Surgery), Chie Kajiwara (Department of Stem Cell Biology and Histology), and Minaka Sato (Department of Stem Cell Biology and Histology) for their skillful technical assistance.
Funding Information:
The authors of this manuscript have conflicts of interest to disclose as described by the . Yoshihiro Kushida, Shohei Wakao, Yasumasa Kuroda, and Mari Dezawa are parties to a co‐development and co‐research agreement with Life Science Institute, Inc. (LSII: Tokyo, Japan). Mari Dezawa and Shohei Wakao have a patent for Muse cells, and the Muse cell isolation method is licensed to LSII. Yoshihiro Kushida, Shohei Wakao, Yasumasa Kuroda, and Mari Dezawa received a joint research grant from LSII. American Journal of Transplantation
Funding Information:
This study was supported by the Grants‐in‐Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (17K10504); and collaborative research development with Life Science Institute, Inc. The authors thank Chikako Sato (Department of Surgery), Yasuko Furukawa (Department of Surgery), Chie Kajiwara (Department of Stem Cell Biology and Histology), and Minaka Sato (Department of Stem Cell Biology and Histology) for their skillful technical assistance.
Publisher Copyright:
© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.
PY - 2021/6
Y1 - 2021/6
N2 - Small-for-size syndrome (SFSS) has a poor prognosis due to excessive shear stress and sinusoidal microcirculatory disturbances in the acute phase after living-donor liver transplantation (LDLT). Multilineage-differentiating stress enduring (Muse) cells are reparative stem cells found in various tissues and currently under clinical trials. These cells selectively home to damaged sites via the sphingosine-1-phosphate (S1P)–S1P receptor 2 system and repair damaged tissue by pleiotropic effects, including tissue protection and damaged/apoptotic cell replacement by differentiating into tissue-constituent cells. The effects of intravenously administered human bone marrow-Muse cells and -mesenchymal stem cells (MSCs) (4 × 105) on liver sinusoidal endothelial cells (LSECs) were examined in a rat SFSS model without immunosuppression. Compared with MSCs, Muse cells intensively homed to the grafted liver, distributed to the sinusoids and vessels, and delivered improved blood chemistry and Ki-67(+) proliferative hepatocytes and -LSECs within 3 days. Tissue clearing and three-dimensional imaging by multiphoton laser confocal microscopy revealed maintenance of the sinusoid continuity, organization, and surface area, as well as decreased sinusoid interruption in the Muse group. Small-interfering RNA-induced knockdown of hepatocyte growth factor and vascular endothelial growth factor-A impaired the protective effect of Muse cells on LSECs. Intravenous injection of Muse cells might be a feasible approach for LDLT with less recipient burden.
AB - Small-for-size syndrome (SFSS) has a poor prognosis due to excessive shear stress and sinusoidal microcirculatory disturbances in the acute phase after living-donor liver transplantation (LDLT). Multilineage-differentiating stress enduring (Muse) cells are reparative stem cells found in various tissues and currently under clinical trials. These cells selectively home to damaged sites via the sphingosine-1-phosphate (S1P)–S1P receptor 2 system and repair damaged tissue by pleiotropic effects, including tissue protection and damaged/apoptotic cell replacement by differentiating into tissue-constituent cells. The effects of intravenously administered human bone marrow-Muse cells and -mesenchymal stem cells (MSCs) (4 × 105) on liver sinusoidal endothelial cells (LSECs) were examined in a rat SFSS model without immunosuppression. Compared with MSCs, Muse cells intensively homed to the grafted liver, distributed to the sinusoids and vessels, and delivered improved blood chemistry and Ki-67(+) proliferative hepatocytes and -LSECs within 3 days. Tissue clearing and three-dimensional imaging by multiphoton laser confocal microscopy revealed maintenance of the sinusoid continuity, organization, and surface area, as well as decreased sinusoid interruption in the Muse group. Small-interfering RNA-induced knockdown of hepatocyte growth factor and vascular endothelial growth factor-A impaired the protective effect of Muse cells on LSECs. Intravenous injection of Muse cells might be a feasible approach for LDLT with less recipient burden.
KW - animal models: murine
KW - basic (laboratory) research/science
KW - cellular transplantation (non-islet)
KW - donors and donation: living
KW - liver transplantation/hepatology
KW - liver transplantation: living donor
KW - regenerative medicine
KW - stem cells
KW - tissue injury and repair
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U2 - 10.1111/ajt.16461
DO - 10.1111/ajt.16461
M3 - Article
C2 - 33350582
AN - SCOPUS:85099379327
SN - 1600-6135
VL - 21
SP - 2025
EP - 2039
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 6
ER -