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2017 ; 26
(5
): 821-840
Nephropedia Template TP
gab.com Text
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English Wikipedia
Muse Cells, Nontumorigenic Pluripotent-Like Stem Cells, Have Liver Regeneration
Capacity Through Specific Homing and Cell Replacement in a Mouse Model of Liver
Fibrosis
#MMPMID27938474
Iseki M
; Kushida Y
; Wakao S
; Akimoto T
; Mizuma M
; Motoi F
; Asada R
; Shimizu S
; Unno M
; Chazenbalk G
; Dezawa M
Cell Transplant
2017[May]; 26
(5
): 821-840
PMID27938474
show ga
Muse cells, a novel type of nontumorigenic pluripotent-like stem cells, reside in
the bone marrow, skin, and adipose tissue and are collectable as cells positive
for pluripotent surface marker SSEA-3. They are able to differentiate into cells
representative of all three germ layers. The capacity of intravenously injected
human bone marrow-derived Muse cells to repair an immunodeficient mouse model of
liver fibrosis was evaluated in this study. The cells exhibited the ability to
spontaneously differentiate into hepatoblast/hepatocyte lineage cells in vitro.
They demonstrated a high migration capacity toward the serum and liver section of
carbon tetrachloride-treated mice in vitro. In vivo, they specifically
accumulated in the liver, but not in other organs except, to a lesser extent, in
the lungs at 2 weeks after intravenous injection in the liver fibrosis model.
After homing, Muse cells spontaneously differentiated in vivo into HepPar-1
(71.1?±?15.2%), human albumin (54.3?±?8.2%), and anti-trypsin
(47.9?±?4.6%)-positive cells without fusing with host hepatocytes, and expressed
mature functional markers such as human CYP1A2 and human Glc-6-Pase at 8 weeks
after injection. Recovery in serum, total bilirubin, and albumin and significant
attenuation of fibrosis were recognized with statistical differences between the
Muse cell-transplanted group and the control groups, which received the vehicle
or the same number of a non-Muse cell population of MSCs (MSCs in which Muse
cells were eliminated). Thus, unlike ESCs and iPSCs, Muse cells are unique in
their efficient migration and integration into the damaged liver after
intravenous injection, nontumorigenicity, and spontaneous differentiation into
hepatocytes, rendering induction into hepatocytes prior to transplantation
unnecessary. They may repair liver fibrosis by two simple steps: expansion after
collection from the bone marrow and intravenous injection. A therapeutic strategy
such as this is feasible and may provide significant advancements toward liver
regeneration in patients with liver disease.