Chimeric Livers: Interspecies Blastocyst Complementation and Xenotransplantation for End-Stage Liver Disease
Hepatic Medicine Evidence and Research,
Год журнала:
2024,
Номер
Volume 16, С. 11 - 29
Опубликована: Фев. 1, 2024
Orthotopic
liver
transplantation
(OLT)
currently
serves
as
the
sole
definitive
treatment
for
thousands
of
patients
suffering
from
end-stage
disease;
and
existing
supply
donor
livers
OLT
is
drastically
outpaced
by
increasing
demand.
To
alleviate
this
significant
gap
in
treatment,
several
experimental
approaches
have
been
devised
with
aim
either
offering
interim
support
to
waiting
on
transplant
list
or
bioengineering
complete
infusing
them
fresh
hepatic
cells.
Recently,
interspecies
blastocyst
complementation
has
emerged
a
promising
method
generating
organs
utero
over
short
timeframe.
When
coupled
gene
editing
technology,
it
brought
about
potentially
revolutionary
transformation
regenerative
medicine.
Blastocyst
harbors
notable
potential
human
large
animals,
which
could
be
used
xenotransplantation
humans,
addressing
scarcity
OLT.
Nevertheless,
substantial
ethical
challenges
still
need
overcome
produce
larger
domestic
animals
like
pigs.
This
review
compiles
current
understanding
outlines
future
possibilities
humans.
Язык: Английский
Generation of salivary glands derived from pluripotent stem cells via conditional blastocyst complementation
Cell Reports,
Год журнала:
2024,
Номер
43(6), С. 114340 - 114340
Опубликована: Июнь 1, 2024
Язык: Английский
Unlocking the therapeutic potential: odyssey of induced pluripotent stem cells (iPSC) in precision cell therapies
International Journal of Surgery,
Год журнала:
2024,
Номер
110(10), С. 6432 - 6455
Опубликована: Июль 4, 2024
This
review
explores
the
application
of
induced
pluripotent
stem
cells
(iPSCs)
in
regenerative
medicine.
The
therapeutic
significance
iPSC-derived
cell
therapy
within
medicine,
emphasizes
their
reprogramming
process
and
crucial
role
cellular
differentiation
while
setting
purpose
scope
for
comprehensive
exploration
therapy.
subsequent
sections
intricately
examine
therapy,
unravelling
diverse
derivatives
iPSCs
striking
a
delicate
balance
between
advantages
limitations
applications.
Mechanisms
action,
revealing
how
seamlessly
integrate
into
tissues,
induce
regeneration,
contribute
to
disease
modeling
drug
screening
advancements
is
discussed.
analysis
extends
clinical
trials,
shedding
light
on
outcomes,
safety
considerations,
ethical
dimensions.
Challenges
concerns,
including
risk
tumorigenesis
scalability
issues,
are
explored.
focus
disease-specific
applications,
showcasing
as
promising
avenue
various
medical
conditions,
supported
by
illustrative
case
studies.
Future
directions
research
needs
outlined,
identifying
areas
further
exploration,
considerations
potential
enhancements
that
will
shape
future
landscape
therapies.
In
conclusion,
this
provides
significant
understanding
therapy's
status,
contemplates
implications
medicine
personalized
treatment
using
iPSCs,
offering
perspective
evolving
field
confines
dynamic
scientific
frontier.
Язык: Английский
Generation of human-pig chimeric renal organoids using iPSC technology
Communications Biology,
Год журнала:
2024,
Номер
7(1)
Опубликована: Окт. 7, 2024
Porcine
organs
and
human
induced
pluripotent
stem
cell
(iPSC)-derived
organoids
as
alternative
for
transplantation
have
garnered
attention,
but
both
face
technical
challenges.
Interspecies
chimeric
organ
production
using
iPSCs
shows
promise
in
overcoming
these
Our
group
successfully
generated
renal
iPSC-derived
nephron
progenitor
cells
(NPCs)
fetal
mouse
kidneys.
However,
the
current
technology
is
limited
to
rodents.
Therefore,
this
study
focused
on
producing
human-pig
organoids,
pigs
are
most
promising
species
xenotransplantation.
Modification
of
existing
culture
systems
enables
continuous
development
species,
resulting
successful
creation
organoids.
Moreover,
method
can
be
applied
generate
humanized
xenogeneic
kidneys
future
clinical
applications.
This
provides
evidence
that
optimizing
conditions
early-stage
kidney
beyond
barriers,
thus
laying
foundation
accelerating
research
fabrication
purposes.
Язык: Английский
Evidence for in vivo mRNA Transport Between Mammalian Cells
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 13, 2024
Abstract
The
prevalence
and
significance
of
intercellular
mRNA
transport
remains
unknown.
Direct
detection
transfer
between
cells
within
an
organism
is
challenging
due
to
technical
limitations
associated
with
transgene
encoded
molecular
labels
cell
sorting
techniques.
In
this
study
we
analyzed
human-to-mouse
xenograft
single-cell
RNA
sequencing
data
identify
mouse
transcripts
in
recovered
human
cells.
murine
transcriptome
analysis
implicates
macrophages
as
a
frequent
donor
type.
We
then
developed
vitro
system
using
RAW264.7
HeLa
HEK293
confirmed
the
Ftl1
from
Overall,
our
provides
compelling
vivo
evidence
for
prevalent
models.
Язык: Английский
Blastocyst complementation generates exogenous donor‐derived liver in ahepatic pigsc
The FASEB Journal,
Год журнала:
2024,
Номер
38(21)
Опубликована: Ноя. 12, 2024
Abstract
Liver
diseases
are
one
of
the
leading
causes
morbidity
and
mortality
worldwide.
Globally,
liver
responsible
for
approximately
2
million
deaths
annually
(1
every
25
deaths).
Many
patients
with
chronic
can
benefit
from
organ
transplantation.
However,
stringent
criteria
placement
on
transplantation
waitlist
shortage
organs
preclude
access
to
patients.
To
bridge
shortfall,
generation
chimeric
human
in
pigs
has
long
been
considered
as
an
alternative.
Here,
we
report
feasibility
approach
by
generating
livers
using
a
conditional
blastocyst
complementation
that
creates
vacant
niche
hosts,
enabling
initiation
organogenesis
through
donor‐derived
pluripotent
cells.
Porcine
fetal
fibroblasts
were
sequentially
targeted
knockin
CRE
into
endogenous
FOXA3
locus
(
)
followed
floxing
exon
1
HHEX
loxP/loxP
locus.
The
knockout
constitutive
GFP
donor
COL1A
CAG:LACZ
2A
EGFP
used
nuclear
donors
generate
host
embryos
somatic
cell
transfer,
complemented
transferred
estrus
synchronized
surrogates.
In
resulting
fetuses,
blastomeres
reconstituted
hepatocytes
confirmed
immunohistochemistry.
These
results
potentially
pave
way
exogenous
hepatogenesis
large
animal
models.
Язык: Английский
Generation of salivary glands derived from pluripotent stem cells via conditional blastocyst complementation
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 15, 2023
Summary
Various
patients
suffer
from
dry
mouth
due
to
salivary
gland
dysfunction.
Whole
generation
and
transplantation
is
a
potential
therapy
resolve
this
issue.
However,
the
lineage
permissible
design
entire
has
been
enigmatic.
Here,
we
discovered
Foxa2
as
critical
for
generating
via
conditional
blastocyst
complementation
(CBC).
linage,
but
not
Shh
nor
Pitx2,
initiated
label
between
boundary
region
of
endodermal
ectodermal
oral
mucosa
before
primordial
formation,
resulting
in
marking
gland.
The
was
agenesis
by
depleting
Fgfr2
under
mice.
We
rescued
phenotype
injecting
donor
pluripotent
stem
cells
into
mouse
blastocysts.
Those
mice
survived
until
adulthood
with
normal
glands
compatible
size
compared
littermate
controls.
These
results
indicated
that
CBC-based
promising
next-generation
cell-based
therapy.
Язык: Английский
Generation of human-pig chimeric renal organoids using iPSC technology
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 20, 2024
Abstract
The
potential
of
using
porcine
organs
and
human
induced
pluripotent
stem
cell
(iPSC)-derived
organoids
as
alternative
for
transplantation
has
garnered
growing
attention.
However,
both
approaches
still
face
technological
challenges.
Interspecies
chimeric
organ
production
iPSCs
is
expected
to
be
another
promising
approach
that
addresses
the
challenges
associated
with
production.
Our
research
group
successfully
generated
human-mouse
renal
by
utilizing
iPSC-derived
nephron
progenitor
cells
(NPCs)
fetal
mouse
kidneys.
current
technology
limited
engraftment
development
capabilities
NPCs,
there
have
been
no
reports
generating
interspecies
in
larger
animals,
only
rodents.
Therefore,
this
study,
we
embarked
on
human-pig
pig
kidney,
which
considered
most
source
humans.
To
construct
a
organoid
culture
system,
first
modified
existing
system
developed
method
enables
survival
continued
species.
This
was
found
applicable
kidney
cells,
ultimately,
produced
organoids.
Furthermore,
can
also
applied
generation
kidneys
future
clinical
applications.
findings
study
serve
foundational
will
greatly
accelerate
humanized
purposes,
are
used
an
evaluation
technique
ensure
quality
NPCs
xenotransplantation.
Язык: Английский
The perspective for next-generation lung replacement therapies: functional whole lung generation by blastocyst complementation
Current Opinion in Organ Transplantation,
Год журнала:
2024,
Номер
29(5), С. 340 - 348
Опубликована: Июль 30, 2024
Blastocyst
complementation
represents
a
promising
frontier
in
next-generation
lung
replacement
therapies.
This
review
aims
to
elucidate
the
future
prospects
of
blastocyst
within
clinical
settings,
summarizing
latest
studies
on
generating
functional
lungs
through
this
technique.
It
also
explores
and
discusses
host
animal
selection
relevant
interspecific
chimera
formation,
challenge
integral
creating
human
via
complementation.
Язык: Английский