Research Spanish scientists create monkey and human chimeras in China
A group of Spanish researchers, led by
Juan Carlos Izpisúa
, from the Gene Expression Laboratory and the Center for Genomics and Bioinformatics of the Salk Institute of La Jolla, in California (United States), has managed to
regenerate
mouse
muscle cells
by activating their precursors myogenic, so that
recovery time from muscle injuries
is
reduced by half
.
The study, published today by Nature Communications, sheds light on the mechanisms underlying muscle growth and regeneration and opens the
prospect of future tissue regeneration in humans
, both to repair
injuries in athletes
and for
loss of muscle mass due to
muscle growth.
aging
or immobilization forced by certain diseases.
Muscle tears are the most frequent injuries and
60% break again after recovery
.
In this new research some
keys
are revealed
about the molecular changes
related to the loss of muscle that the aging process implies and that contributes in many cases to disability.
Led by the Spanish Juan Carlos Izpisúa, the work has been carried out in collaboration with the Research Unit of the Traumatology Department of the CEMTRO Clinic, in Madrid and with the San Antonio de Murcia Catholic University (UCAM).
In fact, it is promoted and financed by UCAM, the Dr. Pedro Guillén Foundation, the Association of Spanish Footballers (AFE) and the MAPFRE Foundation, and also has the collaboration of the Spanish Olympic Committee (COE).
'Yamanaka Cocktail'
To unravel the aforementioned mechanisms, researchers have used
Yamanaka's
well-known
'cocktail'
: a combination of proteins (transcription factors) that control how DNA is copied for translation to other proteins, in this case to convert
skin cells into others that are pluripotent
, that is, they have the ability to become different types of cells.
Muscle regeneration is mediated by muscle stem cells, called
satellite cells
.
These are located in a niche between a layer of connective tissue (basal lamina) and the muscle fibers (myofibers).
By studying them in mice, the researchers have seen that, in a specific model of myofibers, adding
Yamanaka factors to those muscles accelerates muscle regeneration
, reducing levels of the Wnt4 protein in the niche and activating satellite cells. However, using the specific model of satellite cells, they did not improve muscle regeneration, which offers
clues about the important role of Wnt4
in this regeneration.
According to Juan Carlos Izpisúa, these findings could lead to
medical treatments
that
target the Wnt4 protein
.
"Our laboratory has developed new gene editing technologies that could be used to
accelerate muscle recovery after injury and improve function
. We could use it to directly reduce Wnt4 levels in skeletal muscle or to block communication between Wnt4. and muscle stem cells. "
MRNA and genetic engineering, next targets
The team is also
studying other ways to rejuvenate cells
, such as
mRNA and genetic engineering
, techniques that could lead to new approaches to tissue and organ regeneration. It is not, therefore, an isolated work, but is part of a
line of study to accelerate muscle regeneration
in which
Pedro Guillén
, professor of Sports Traumatology at UCAM and founder and director of the CEMTRO Clinic.
The group had
previously shown that the manipulation
of these factors can rejuvenate cells and promote regeneration in mice, according to a study published in 'Cell' in 2016. "So we already did a
cell reprogramming with
aged
mice
from
Carlos López's
laboratory-
Otín
, from the University of Oviedo, to whom we injected these molecules and they began to run because their cellular tissues rejuvenated ", comments Guillén, emphasizing that it was the
basis of the new scientific milestone.
The experiment was carried out this time with
young mice
, which were
injected with a 'cassette' of Yamanaka molecules
without liberation in the tibialis anterior muscle and in the calf, but previously
degenerated with cardiotoxin
to produce a severe acute injury. They were then injected with doxycycline to release the Yamanaka factors, which decreased the Wnt4 protein, activated satellite stem cells, and
produced more muscle fibers
.
"The
immediate production of many myofibrils is what shortens the healing time of the injury
, both in an injured fiber and in a fiber
degenerated by age
or
by some disease
. What has become clear is that the muscle took twice as long to recover if we did not apply doxycycline ", clarifies the traumatologist, stressing that" all muscle is muscle ", that is, this
cell therapy would serve for any area of the musculoskeletal system
, either because it is injured or deteriorated by age.
Possible universal therapy?
Guillén already almost envisions the possibility of
converting this animal experimentation into a treatment for injured muscles
, which could be virtually by means of injections of the component used in the research, "but first it is necessary to
show that it is not toxic or produces tumors
", clarifies the teacher.
This opens up, and in his opinion, a future field of clinical trials that could favor the more effective and faster recovery of
people with sports injuries
, mainly athletes, but also of
elderly people
with muscles deteriorated by age, or of
patients with forced immobilization
by casts or other causes. "For example,
covid-19 is leading to long periods of hospitalization
and it takes a long time to regain lost muscle mass."
For Guillén, these achievements have been possible "thanks to the
value of civil society,
in which we have to believe", since the study has had the
main
impulse and funding
of UCAM, in addition to the support of entities such as the Association of Spanish Soccer Players (AFE), the Mapfre Medicina Foundation, the Pedro Guillén Foundation itself and the collaboration of the Spanish Olympic Committee (COE) ".
According to the criteria of The Trust Project
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