För 9 timmar sen offentliggjordes en studie från San Jose State University som berör den Regenerativa Medicinen, mer specifikt ett skadat hjärtas förmåga att läka med stöd av Reg, Med.
Because we know that NE induces hypertrophy, this data validates the use of the novel HoloMonitor® live cell imaging microscope. The benefits of this technology include 3D visualization and quanti-fication of living cells. Tissue integrity is upheld due to the ability to visualize the cells without labels or stains/dyes. Additionally, the same sample can be used for different assays and quantifications, thus saving laboratory resources (PHI, n.d.).
Men till studien betitlad :
Abstract
Heart disease continues to be the leading cause of death in the United States.
Humans are unable to regenerate their heart tissue following an injury.
However, neonatal mice are able to regenerate their heart tissue when
cardiomyocytes (CMs) proliferate.
This regenerative ability is lost
approximately one week after birth when proliferating mononucleated CMs
become binucleated and can no longer complete the cell-cycle.
Recent
studies have shown the combined inhibition of thyroid hormone (T3) and
norepinephrine (NE) increases CM proliferation, promotes heart
regeneration, and reduces cell size in vivo.
Using digital holographic
microscopy, the aim of this study was to (1) validate the novel Holomonitor
approach and (2) visualize and quantify the effects of T3 and NE on
cardiomyocyte size.
CMs were isolated from neonatal rats 1 to 2 days after
birth which were then treated with NE and/or T3 in serum-free culture.
Live
cell imaging was visualized utilizing digital holographic microscopy and
changes in CM dynamics and morphology were quantitatively tracked and
analyzed using HoloMonitor software.
The results from this study validate
the HoloMonitor technology by demonstrating that NE induced
hypertrophy in CMs after 12 hours.
Our results also demonstrate the ability
of HoloMonitor technology to differentiate between CMs and non-CMs in
living, serum-free culture, while also studying and quantifying their
dynamics in vitro. Lastly, our data shows that T3 has little effect on CM
growth and that NE decreased CM motility.
Introduction
Heart disease plagues the United States and continues to be the
leading cause of death for Americans (CDC, 2022).
Damage to heart tissue
is especially detrimental to one's health due to its inability to regenerate;
thus, patients are left with a weaker heart for the rest of their lives.
However,
this lack of cardiac regenerative ability is not universal to all animals.
Unlike adult mammals, which have a limited capacity to regenerate
their hearts after injury, newborn rodents are capable of cardiac tissue
regeneration.
Such regeneration relies on the proliferation of heart muscle
cells called cardiomyocytes (CMs) (Porrello et al, 2011). Mice lose the
ability to regenerate their heart tissue within the first week after birth when
CMs transition from proliferating mononucleated cells to binucleated cells
which are incapable of completing the cell cycle (Soonpa et al, 1996).
Following this transition of mononucleated to binucleated CMs,
hypertrophy is the cause for increased heart mass.
It is known that inhibition of thyroid hormone (TH) and adrenergic
receptor (AR) signaling in postnatal mice CMs causes them to not
binucleate and not exit the cell cycle; therefore, the cell can regenerate.
Conversely, although the cellular mechanism is unknown, it has been
established that the synergistic activation of both TH and AR signaling will
prevent cardiomyocyte proliferation in vivo (Payumo and Chen et al, 2021).
It is known that norepinephrine (NE), a hormone that binds to adrenergic
receptors, induces CM hypertrophy.
However, little is known about the
synergistic activation of TH and AR signaling on cardiomyocyte size. We
suspect that T3 and NE signaling activation will promote hypertrophic
growth in CMs.
Using digital holographic microscopy, the goal of this research is to
quantitatively visualize the hormonal effects of activated T3 and NE
signaling in newborn mice CMs (in vitro) pertaining to hypertrophic growth
dynamics. Specifically, we aim to determine if T3 and NE signaling
interactions promote cardiomyocyte hypertrophy.
Because the cellular mechanism of cardiomyocyte proliferation is
unknown, this research aims to help answer the question: “Does
cardiomyocyte hypertrophy effect proliferation?”
Answering this question will better inform efforts moving forward to identify the mechanism of CM
proliferation. This will have a monumental impact on the future of cardiac
regenerative medicine.
Discussion
Data obtained from Figure 1 allowed us to distinguish between CM
and non-CMs in unfixed living tissue samples in real-time. This was crucial
to the study as there appeared to be different types of cells found in cardiac
tissue other than CMs.
Data from Figure 2 showed that T3 treatment does not have a
significant effect on CM size and that the only significant increase in
average optical volume was with the NE-treated CMs. Because we know
that NE induces hypertrophy, this data validates the use of the novel
HoloMonitor® live cell imaging microscope. The benefits of this
technology include 3D visualization and quanti-fication of living cells.
Tissue integrity is upheld due to the ability to visualize the cells without labels or stains/dyes. Additionally, the same sample can be used for
different assays and quantifications, thus saving laboratory resources (PHI,
n.d.).
Conclusion
Holographic microscopy is a novel approach to study living, labelfree cardiomyocyte (CM) dynamics in vitro in real-time and is also able to
distinguish CMs from non-CMs. Validation of this technology was
achieved by showing that NE induces hypertrophy in CMs over time. We
also showed that NE suppressed CM motility, which was unexpected.
Lastly, our results also show that T3 treatment had little effect on CM
hypertrophic growth dynamics.
Min kommentar
Denna studie kommer ytterst lämpligt i tiden. Här visar forskaren hur användbar HoloMonitor är enbart för studier på celler för hjärtvävnad åstadkomna genom Regenerativ Medicin. Med studien får vi ett kvitto på hur central HoloMonitor kommer vara för denna framtida superteknologi Reg. Med.
Vi kan även lista ut att det redan idag bedrivs avancerad forskning inom området.
Genombrottet ser inte ut att vara alltför långt bort.
Mellan raderna förstås det att studien ev är ett beställningsjobb i syfte att validera HoloMonitor som användbar för Reg. Med. Svaret forskaren ger är otvetydligt. Läs abstractets sista stycke.
PHI kommer ha stor nytta av denna studie.
Mvh the99
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