| RRC ID |
64144
|
| Author |
Shono Y, Kushida Y, Wakao S, Kuroda Y, Unno M, Kamei T, Miyagi S, Dezawa M.
|
| Title |
Protection of liver sinusoids by intravenous administration of human Muse cells in a rat extra-small partial liver transplantation model.
|
| Journal |
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.
|
| Volume |
21(6)
|
| Pages |
2025-2039
|
| Published |
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
|
| Resource |
| DNA material |
pcDNA3 Venus-Akaluc (RDB15781) |
