RRC ID 64144
著者 Shono Y, Kushida Y, Wakao S, Kuroda Y, Unno M, Kamei T, Miyagi S, Dezawa M.
タイトル Protection of liver sinusoids by intravenous administration of human Muse cells in a rat extra-small partial liver transplantation model.
ジャーナル Am J Transplant
Abstract 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.
巻・号 21(6)
ページ 2025-2039
公開日 2021-6-1
DOI 10.1111/ajt.16461
PMID 33350582
PMC PMC8248424
MeSH Alprostadil Animals Capillaries Cell Differentiation Endothelial Cells Humans Infusions, Intravenous Liver Liver Transplantation* Living Donors Microcirculation Rats Vascular Endothelial Growth Factor A
IF 7.338
リソース情報
遺伝子材料 pcDNA3 Venus-Akaluc (RDB15781)