Article.
Nouveaux progrès de la biologie synthétique
Jean-Paul Baquiast 16/01/2017
Un article de Nature, référencé
http://www.nature.com/articles/ncomms13724,
annonce que des scientifiques américains et chinois
associés (Pourvu soit dit en passant que Donald Trump
ne parle pas de trahison), viennent de créer une
cellule souche cardiaque synthétique, offrant les
mêmes possibilités thérapeutiques que
celles d'une cellule souche biologique, sans les risques
associés.
En effet, contrairement aux cellules souches
biologiques, elle n'a pas la possibilité de se reproduire,
ce qui prévient l'apparition possible de tumeurs.
Elle n'a pas non plus la fragilité de ses homologues
biologiques, qui nécessite de nombreuses précautions
avant qu'elles soient utilisables.
Dans un tube à essai, les chercheurs
ont créé ce qu'ils ont nommé des “cell-mimicking
microparticles” (CMMPs) et les ont testées
sur un modèle de souris présentant des anomalies
au niveau du tissu cardiaque. La cellule souche synthétique
opère de la même façon qu'un vaccin
désactivé. Elle franchit les défenses
immunitaires, s'attache au tissu cardiaque, libère
des facteurs de croissance et peut ainsi réparer
les tissus atteints.
La technologie serait aussi reproductible
dans le cas d'autres types de cellules souches, ce qui lui
ouvrirait des perspectives considérables concernant
dans un premier temps la réparation de divers autres
organes.
Les chercheurs ne le suggèrent pas,
mais il est possible d'imaginer le rôle que ces cellules
pourraient jouer ultérieurement dans la fabrication
de cellules synthétiques, autrement dit à
terme d'organismes synthétiques complets.
Légende
(a) Overall biochemical
design and study model of CMMPs. MPs (that is, Control MP1)
were fabricated from PLGA and conditioned media of human
CSCs, then MPs were cloaked with membrane fragments of CSCs
to form CMMPs. Control MP2 was fabricated by cloaking empty
PLGA particles with CSC membranes. The therapeutic potential
of CMMPs was tested in a mouse model of myocardial infarction.
(b,c) Texas red succinimidyl ester-labelled MPs (b, red)
were cloaked with the membrane fragments of green fluorescent
DiO-labelled CSCs (b, green) to form CMMP (c, red particle
with green coat). Scale bar, 20?µm. (d,e) SEM revealed
the CSC membrane fragments on CMMPs (e) but not on Control
MP1 (non-cloaked MP) (d). Scale bar, 10?µm. (f,g)
Major human CSC markers CD105 (f) and CD90 (g) were positive
on CMMPs and Control MP2 but not on non-cloaked Control
MP1, indicating the successful membrane cloaking on CMMPs.
(h) CMMPs, Control MP1 and Control MP2 have similar sizes
to those of CSCs. n=3 for each group. (i) CMMPs and Control
MP2 carried similar surface antigens as CSCs did. n=3 for
each group. (j–l) Similar release profile of CSC factors
(namely vascular endothelial growth factor (VEGF), insulin-like
growth factor (IGF)-1 and hepatocyte growth factor (HGF))
was observed in CMMPs and Control MP1, indicating membrane
cloaking did not affect the release of CSC factors from
CMMPs and Control MP1. n=3 for each time point. All data
are mean±s.d. Comparisons between any two groups
were performed using two-tailed unpaired Student’s
t-test. Comparisons among more than two groups were performed
using one-way ANOVA followed by post hoc Bonferroni test.
Abstract
Therapeutic microparticles functionalized with biomimetic
cardiac stem cell membranes and secretome
Stem cell therapy represents a promising strategy in regenerative
medicine. However, cells need to be carefully preserved
and processed before usage. In addition, cell transplantation
carries immunogenicity and/or tumorigenicity risks. Mounting
lines of evidences indicate that stem cells exert their
beneficial effects mainly through secretion (of regenerative
factors) and membrane-based cell-cell interaction with the
injured cells. Herein, we fabricated a synthetic cell-mimicking
microparticle (CMMP) that recapitulates stem cell functions
in tissue repair. CMMPs carries similar secreted proteins
and membranes as genuine cardiac stem cells do. In a mouse
model of myocardial infarction, injection of CMMPs leads
to preservation of viable myocardium and augmentation of
cardiac functions similar to cardiac stem cell therapy.
CMMPs (derived from human cells) do not stimulate T cells
infiltration in immuno-competent mice. In conclusion, CMMPs
act as “synthetic stem cells” which mimic the
paracrine and biointerfacing activities of natural stem
cells in therapeutic cardiac regeneration.
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