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Protection of liver sinusoids by intravenous administration of human Muse cells in a rat extra‐small partial liver transplantation model
Author(s) -
Shono Yoshihiro,
Kushida Yoshihiro,
Wakao Shohei,
Kuroda Yasumasa,
Unno Michiaki,
Kamei Takashi,
Miyagi Shigehito,
Dezawa Mari
Publication year - 2021
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.16461
Subject(s) - medicine , sinusoid , mesenchymal stem cell , transplantation , hepatocyte growth factor , stem cell , bone marrow , haematopoiesis , microbiology and biotechnology , hepatocyte , cell therapy , pathology , cancer research , receptor , biology , in vitro , biochemistry
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 × 10 5 ) 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.