Mesenchymal Stem Cells As Targeted Drug

In: Advances in Medicine and Biology ISBN: 978-1-53614-722-3
Editor: Leon V. Berhardt © 2019 Nova Science Publishers, Inc.
Chapter 5
MESENCHYMAL STEM CELLS IN

THE REGENERATION OF DAMAGED
MYOCARDIUM: MODERN RESEARCH
TRENDS AND CLINICAL PROSPECTS
Muhammad Shareef Masoud 1, , PhD, Uzair Ahmed1,

Muhammad Qasim1, PhD, Usman Ali Ashfaq1, PhD,
Mahmood-ur-Rahman1 PhD
and Muhammad Tariq2 PhD
1
Department of Bioinformatics and Biotechnology,
Government College University Faisalabad, Pakistan
2
Department of Biotechnology, Mirpur University of Science
and Technology, Mirpur AJK, Pakistan
*
Corresponding Author Email: masoudshareef@gmail.com; masoudshareef@gcuf.edu.pk.
Complimentary Contributor Copy

114 Muhammad Sh. Masoud, Uzair Ahmed, Muhammad Qasim et al.
ABSTRACT
Cardiovascular diseases are the main reason behind most of the

deaths occurring worldwide and there is no promising treatment available
to treat cardiomyopathies except some pharmacological and surgical
interventions including a heart transplant. Among different cellular
therapies aimed for the regeneration of damaged myocardium,
Mesenchymal stem cells (MSCs) have proved to be a sagacious choice
due to its multiple properties like potential to differentiate into different
cell lineages, easier to extract and culture, paracrine production and
immunomodulation. These are proven as to be the potential cell therapy
following several animal studies as well as clinical trials. MSCs have
been transplanted through multiple routes and have resulted in an increase
in vessel growth, reduced scar size and improved cardiac function by
various molecular mechanisms. On the other hand, MSC-derived
exosomes can also protect myocardium from injury and induce healing of
damaged heart tissue. Although MSCs have attained a significant
appreciation but still there are many challenges to overcome before it
goes to clinic. This review focus on the recent development and modern
trends in use of MSCs for the regeneration of damaged myocardium.
Keywords: Mesenchymal stem cells, myocardial ischemia, exosomes,

biomaterials, cellular scaffolds, paracrine effect
INTRODUCTION
Cardiovascular diseases have become a major cause of deaths in the

world and a striking problem to deal with because these are the most
common cause of death worldwide (Pandey et al., 2017) (Fikry, Hassan,
and Gad 2017) (Heidenreich et al., 2013). There are certain types of heart
diseases like ischemic heart disease and non-ischemic heart disease, but
ischemic heart failure, also known as coronary artery disease(CAD) is the
most common cause of cardiac deaths among the people (Golpanian et al.,
2016). Ischemia has more than 40% death rate in European Union (EU)
affecting men and women equally (Kastrup et al., 2016). Ischemia is the
imbalance between the supply of oxygen to a certain part of the heart and
the amount of oxygen required. This imbalance is due to the total blockage

Mesenchymal Stem Cells … 115
of a vessel, which leads to necrosis of heart tissue and gradually cause

angina or dyspnea that can be observed in cold weather or due to emotional
stress. Whereas a sudden blockage of vessels can cause acute chest pain
(angina) thus reducing the quality of life and health. Diabetes mellitus,
along with ischemic heart disease, makes heart failure more lethal to the
patients because 27% of patients having both of diseases die within 2 years
(Qayyum, Mathiasen, and Kastrup 2014). Ischemia can be cured if
angiogenesis occur and new vessels are formed (Qayyum, Mathiasen, and
Kastrup 2014) (Dimitropoulos 2014).
Mesenchymal stem cells (MSC) are multipotent stem cells that can
differentiate into many cell lines like cardiomyocytes, osteoblasts,
endothelial and vascular tissues. They can be easily isolated from a variety
of tissues like bone marrow, adipose tissues, umbilical cord tissue and
blood. They can be cultured in the lab and differentiated into different cell
types. Therefore, due to their differentiation ability the use of stem cells as
a therapeutic agent for heart failure was emerged over 2 decades on
animals and over 10 years clinical trials are also being done (Golpanian
et al., 2016). MSCs are unique because they have regeneration capabilities
and also act as immunosuppressant as they express MHC class 1 at low
levels. Due to this reason MSCs do not interact with the immune cells
(Melief et al., 2013). In this review, we will explore MSCs and their
desirable therapies for heart failure and implement the potential use of
MSCs as cellular therapeutics in clinical practices.
CURRENT TREATMENT OF HEART DISEASES
Despite of most common disease having large death rate, heart

diseases have no promising treatments currently exist to reverse the effect
of heart failure. In heart failure, last stage severe signaling mechanisms
cause cardiac remodeling leading to myocardial dysfunction. Currently
only a limited options of treatment are available regarding heart failure like
cardiac transplantation, pharmacological interventions, mechanical
circulatory support and cardiac resynchronization therapy (Garg et al.,

2013)(Kamdar et al., 2013). Cardiac transplant, which is very expensive, is

only possible if a donor heart is available and it is also prone to immune
rejection (J. S. Da Silva and Hare 2013). Cellular therapy is a strong
candidate for future treatment of heart diseases because it targets at
molecular level to improve heart’s function and promotes neoangiogenesis.
Cell based therapy will allow a greater number of patients to benefit from
it rather than other treatment options. Among cellular therapies, MSCs
represent a strong option to heal heart diseases in regenerative medicine
that could be the best option for treatment in future regarding heart failure.
MESENCHYMAL STEM CELLS
MSCs are multipotent adult stem cells that have the potential to
differentiate into multiple cell lineages according to provided conditions.
Minimum criteria for MSC identification is > 95% cell population positive
for CD105, CD73 and CD90 surface markers and less than 2% negative for
CD45, CD34, CD14 or CD11b, CD79a or CD19 and HLA class II surface
markers and they are adherent to plastic under certain conditions (El Sayed
Shafei et al., 2017) (Horwitz et al., 2005).
Figure 1. Differentiation of MSCs into different cell lines.

MSCs can differentiate into chondroblasts, adipocytes and osteoblasts.

Implanting MSCs into the infarcted heart significantly improves the rate of
recovery and cardiac function of heart (Peng et al., 2016). Therefore,
MSCs prove to be promising cell type because of the fact that they
promote angiogenesis and are easily differentiable into cardiomyocytes
(Guijarro et al., 2016).
MSCs from different sources share common characteristics. These
have been identified in a number of organs like adipose tissue, Wharton
jelly, bone marrow, umbilical cord, heart and peripheral blood (Hass et al.,
2011). Bone marrow and adipose tissue are the most common sources from
where MSCs can be easily harvested in large quantities.
MSC IN HEART REGENERATION
MSCs had used for decades as candidate for regenerative medicine and
are still under investigation because of their angiogenic properties that
make them a notable therapeutic agent in the treatment of heart disorders.
It is identified that MSCs transplantation into infarcted region of the heart
can have infarct limiting effects as well as cardiac regeneration in both
experimental and clinical trials. MSCs transplantation also increases the
vessel growth through angiogenesis and survival rate of nearby
cardiomyocytes due to paracrine factors, but some challenges still exist to
use MSCs as fully approved medicine (El Sayed Shafei et al., 2017).
Bone Marrow and Adipose Derived MSCs

in Heart Regeneration
Bone marrow derived MSCs (BM-MSCs) can be used as a potential

therapeutic agent to cure heart diseases (Ayatollahi et al., 2012). The
combination of BM-MSCs with Interleukin-10 (IL10), which is an anti-
inflammatory cytokine, may suppress inflammatory response, which
results in the functional recovery of left ventricle (LV). IL10 provides an

important role in cell survival under ischemia, thus it is very useful to

combine it with MSCs to create results that are more promising. Meng
et al., 2018 studied the overexpression of IL10 induced in bone marrow
derived MSCs (BM-MSCs) using adenoviral transduction and transplanted
it to rat model with myocardial ischemia. After 4 weeks of transplantation,
the cell viability was enhanced and the rate of apoptosis was decreased due
to overexpression of IL10 that can exert a synergistic effect to alleviate the
cardiac injury during ischemia. Bao et al., 2017 administered BM-MSCs
and C-kit+ cardiac stem cells (CSCs) by intramyocardial injection in rats
with 28 days myocardial infarction. As a result, BM-MSCs and CSCs
improved ventricular function and reduced the infarct size considerably.
Moreover, the transplant also inhibited the apoptosis rate and improved
rate of recovery in paracrine manner. BM-MSCs and CSCs when
combined showed results that were more promising in increased levels of
multiple pro-angiogenic factors than BM-MSCs or CSCs transplanted
individually. Gao et al., 2017 transplanted BM-MSCs into rats with
radiation-induced cardiomyopathy and found that it increased myocardial
function. By studying the expression of PPAR-a, TGF-b, PPAR-c, IL-8,
and IL-6 they found out that BM-MSCs reduced the inflammatory
response and lessened the effects of radiation induced cardiomyopathy.
Moreover, the expression of DNA ligase4, H2AX and TP53BP1, proteins
associated with DNA repair, were up regulated and concentration of
growth factors like IGF, CXCR4, VEGF, and SDF-1 were also increased in
rat’s heart. Therefore, BM-MSCs can alleviate radiation-induced
cardiomyopathy via DNA repair and can be a promising therapeutic agent
for heart diseases. Carmona et al., 2017 isolated BM-MSCs and bone
marrow (BM) derived mononuclear cells (MNCs) from rat bone marrow
and injected them into rats with dilated cardiomyopathy via
intramyocardial injection randomly. BM- MSCs induced improved cardiac
fiber and decreased fibrotic tissue, which elevated LVEF as compared to
BM-MNCs which showed no statistically significant results. Fikry et al.,
2017 examined the therapeutic effects of BM-MSCs or adipose derived
mesenchymal stem cells (AD-MSCs) and transplanted them into
methotrexate induced cardiac fibrosis in rats. The animals treated by BM-

MSCs/AD-MSCs exhibited antifibrotic, antioxidant and antiapoptotic

effects in the deteriorated portion of heart and hence proposed to be a
remarkable therapeutic agent to treat cardiac fibrosis. BM-MSCs and AD-
MSCs holds potential to induce regeneration and angiogenesis in cardiac
tissue among other types of MSCs because of ease in their availability and
culturing.
Umbilical Cord and Wharton Jelly Derived MSCs

in Heart Regeneration
Umbilical cord and Wharton jelly contain a good storage of MSCs and
same therapeutic potential as shown by BM-MSCs or AD-MSCs.
Extraction of MSCs from the umbilical cord is painless, which serves as an
advantage of umbilical cord MSCs (Nagamura-Inoue 2014). Zhang et al.,
2018 studied human umbilical cord MSCs (HuMSCs) derived from
Wharton Jelly. Cultured HuMSCs were injected intravenously to rats
having myosin induced myocardial fibrosis. HuMSCs reduced fibrosis and
restored cardiac function after 28 days of transplantation. Improved tissue
integrity and reduced fibrosis was determined by Masson’s staining.
Moreover western blot analysis indicated the expression of TNF-α and
TGF-β was reduced which are major agents in signaling pathways that
induce myocardial fibrosis. Mao et al., 2017 also studied HuMSCs
administered intramuscularly 4 week to dilated cardiomyopathic rats. The
left ventricular ejection fraction (LVEF) and cardiac function was
improved by the injection of HuMSCs. This showed that intramuscular
administration of HuMSCs could alleviate the impairment of cardiac
function and protect myocardium. Abd Allah et al., 2017 transplanted
HuMSCs in rats with 2- week doxorubicin (DOX) induced
cardiomyopathy. The rats treated with HuMSCs restored cardiac damage
while reactive oxygen species became normal. The results showed that car-
diotoxicity was lowered as followed by structural and functional
improvement of myocardium. Rabbani et al., 2017 combined human
Wharton jelly mesenchymal stem cells (HWJMSCs) with a cocktail of

compounds like polyethylene glycol, chitosan and hyaluronic acid. He

mixed them with scaffold and injected to the region of defect in heart in a
rabbit model. HWJMSCs showed promising results by lowering the region
of defect and improved myocardial function. A great deal of
neoangiogenesis took place and cardiomyogenesis was observed in the
cells. Razavi Tousi et al., 2016 isolated human Amniotic mesenchymal
stem cells (hAMSCs) and injected them into isoproterenol-induced
myocardial infarction in rats. As a result, the LVEF was increased
significantly, which was checked via echocardiography. Moreover, heart
performance enhanced and the level of fibrotic tissue was decreased
significantly. Liu et al., 2016 transplanted HuMSCs intracoronary into
ameroid constrictor induced myocardial ischemia in a pig model. After 4
weeks of transplantation, the LVEF was significantly increased and
thickening of the left ventricle wall was also observed. As result, the
fibrosis and apoptosiswere significantly reduced and myocardial perfusion
was enhanced in a pig model. MSCs from umbilical cord tissue can be very
useful because they can be extracted from the placenta after birth that
makes it painless; however, culturing them is quite difficult and requires
more refinement.
Cardiac MSCs in Heart Regeneration
Cardiac mesenchymal cells (CMCs) are organ specific stem cells that
are present in the heart (Cencioni et al., 2017). After myocardial ischemia,
due to loss of cardiomyocytes, adult MSCs are converted into CMCs and
homed to the damaged heart, thus regenerating it by promoting
angiogenesis and scar formation naturally (Klopsch et al., 2017). Guo
et al., 2017 administered rat CMCs into a rat with 3-weeks old myocardial
infarction. Two groups were formed; one group of rats was given a single
dose of CMCs and other group was administered with three repeated doses
of CMCs. In the multiple dose group, the LV function was improved and
exhibited less collagen formation in healthy regions as compared to the
single dose group. This indicated that in ischemic myopathy repeated

dosage of CMCs provided better results than a single dose of CMCs.

Czapla et al., 2016 isolated CMCs having CD105+ and CD34- phenotype
from human hearts and transplanted them into a rat model with ischemia.
The CMCs showed very less rejection rate and improvement in LVEF was
seen. Moreover, reduction of scar and fibrotic tissue along with an increase
in the number of blood vessels were observed. Due to these properties
CMCs with CD105+ and CD34- phenotype holds a great therapeutic
potential for essential healing of infarcted heart.
MSC DELIVERY VIA BIOMATERIALS

AND CELLULAR SCAFFOLDS
Biomaterials and cellular scaffolds may provide efficient delivery

systems that can make MSCs more efficient and innovative for the
treatment of cardiomyopathies. When MSCs are administered
intravenously, these may home to the other damaged tissue rather than
heart while in intracoronary delivery MSCs are administered directly into
scar which lacks proper blood supply hence MSCs would not be very
effective in this setting (Pandey et al., 2017). Therefore, scientists used
MSCs in combination with some biomaterials in preclinical trials and it
showed very encouraging results. Investigators injected MSCs combined
with self-setting salinized hydroxypropyl methylcellulose into the rats with
myocardial infarction. As a result, the LV remodeling and a reduction in
scar tissue was observed, which proved the efficacy of hydroxypropyl
methylcellulose used with MSCs and resulted in increase in the homing of
MSCs to the site of infarct (Mathieu et al., 2012). In another trial, MSCs
combined with in situ cross-linked alginate hydrogel improved the life and
retention of transplanted cells into myocardium. Alginate hydrogel
promoted viability and paracrine potential of AD-MSCs and may be used
as a source to enhance MSCs delivery because of non-immunogenic
properties of the gel (Follin et al., 2015). In a similar study, MSCs
encapsulated in alginate hydrogel were injected in infarcted rat model and

they decreased the infarct size and improved cardiac function significantly
(Levit et al., 2013).
Several studies are in progress on cellular scaffolds as delivery
mechanisms. A scaffold is an engineered material that can contribute to
new tissue development via desirable cellular interactions. The ideal
scaffold would also allow paracrine signaling and allow the cells to release
their secretions. In a study a viable biodegradable three-dimensional
fibroblast constructs (3DFC) were transplanted into rats with myocardial
infarction and promoted angiogenesis as well as revealed hemodynamic
improvements in heart (Lancaster et al., 2010; Thai et al., 2009).
Figure 2. Different delivery settings for MSCs.
A scaffold could provide a better setting in the surrounding infarct and

works in conjunction with MSCs to promote cellular repairs.
MSC DERIVED EXTRACELLULAR VESICLES

AND EXOSOMES
Recently it is suggested that extracellular vesicles (EVs) mediates the

paracrine function of MSCs (El Sayed Shafei et al., 2017). EVs can be

subdivided into many subtypes such as exosomes and microvesicles,

whereas exosomes are most abundant subtype present. When a
multivesicular body fuses with the plasma membrane, exosomes releases,
whereas cell membrane directly releases microvesicles. At first EVs were
thought to be a cell disposal mechanism but now researchers have found
out they are also responsible in mediating cell to cell communication,
proliferation and cell differentiation by transferring proteins, mRNAs,
lipids and miRNA between different cells (Rani et al., 2015; De Jong et al.,
2014; EL Andaloussi et al., 2013). MiRNA are post-transcriptional
regulators, approximately 22 nucleotides long that control important
cellular processes within eukaryotic cells. The miRNA based therapeutics
can enhance MSC differentiation, cardiac remodeling and reduce apoptosis
in patients with myocardial ischemia (SCALBERT and BRIL 2008;
Fasanaro et al., 2010; Ohtani and Dimmeler 2011). MSCs derived
exosomes can protect the heart from injury and promote angiogenesis as
well as cardiac remodeling. A study showed that the protection of MSCs
from cell death is partially mediated by miRNA-221 contained within EVs
(Yu et al., 2013). Similarly BM-MSC derived exosomes promote
angiogenesis when used in combination of cardiac progenitor cells (CPCS)
(Sahoo et al., 2011; Vrijsen et al., 2010). In another study, MSC derived
exosomes were injected in a rat model of cardiac ischemia and as a result,
they found out a reduction in the size of the infarct as well as MSCs
derived exosomes provided protection to heart (Lai et al., 2010). MSCs,
preconditioned with miRNA-17-92 and miR-29a, enhanced the cardiac
remodeling, promote angiogenesis and differentiation of MSCs into
cardiac cells that are essential for the repair of myocardium (Wen et al.,
2012).
CLINICAL TRIALS
To ensure the safety and efficacy of MSCs in treatment of myocardial

infarction, several trials are being held clinically (Hare 2009; Trachtenberg
et al., 2011). Mostly, the data available on MSC based treatment is to treat

myocardial ischemia and very little work has done on the treatment of non-
ischemic heart failures using MSCs. In fact MSCs can be used for ischemic
and non-ischemic cardiomyopathies with different approaches that can lead
to promising results (Hare et al., 2017; Patel et al., 2016). MSCs shows
many potential benefits like, LV remodeling, improvement in myocardial
function, enhanced LVEF and coronary perfusion when used as a
therapeutic agent for treatment of heart failures. However these benefits
appears to be short termed rather and the long term benefits still remain a
question in cell based therapies (Amado et al., 2005; Hare et al., 2009;
Quevedo et al., 2009; Schuleri et al., 2008; G. V. Silva et al., 2005).
With the increase in popularity of MSCs, many clinical trials have
emerged recently and some of them are completed. Several studies have
been attempted to use MSCs for their qualities like angiogenesis and
improvement in cardiac function in acute and chronic cardiomyopathies.
Initial trials concentrated on the events closer to the time of infarct with
MSCs used to prevent myocardial ischemia (Hare et al., 2009; Richardson
et al., 2013). Clinical trials declared MSCs to be safe and without any risk
to initiate any adverse effect. Moreover, in MSC based treatment, patient
shows improved exercise tolerance (Tse et al., 2003; Kamdar et al., 2013;
Verbrugge et al., 2013; Lenzen et al., 2005). The main factor in successful
treatment is route of delivery of MSCs to heart that remains the main point
of interest for clinicians and remain the area, which requires most
investigations. Initial studies used intracoronary delivery as standard
method for acute cardiomyopathies (Li et al., 2016). The main limitation of
this delivery method is that cells rapidly washes out. Many attempts have
been made to find alternative approaches and scientists have tested
intravenously administered allogeneic MSCs in small studies for non-
ischemic heart failures (Butler et al., 2017).
Allogeneic MSCs are isolated from other individuals, whereas
autologous MSCs are isolated from the same individual. The POSEIDON-
DCM trial is the random comparison between allogeneic and autologous
MSCs for non-ischemic heart failures, delivered transendocardially (Hare
et al., 2012).

Table 1. Clinical trials using MSCs to treat cardiomyopathies
Study title Patient Phase Results Trial Citations

Enrolled Identifier
The Percutaneous Stem Cell Injection 31 participants Phase I/II, Improved quality of NCT01087996 (Hare et al., 2012)
Delivery Effects on Neomyogenesis Randomized life, enhanced
Pilot Study LVEF, no adverse
(The POSEIDON-Pilot Study) effect
C-Cure Clinical Trial 240 participants Randomized Cardiopoietic stem NCT00810238 (Bartunek et al.,
cell are safe, showed 2013)
benefits
The Transendocardial Autologous Cells 65 participants Phase I/II, MSCs NCT00768066 (Heldman et al.,
(hMSC or hBMC) in Ischemic Heart Randomized, transendocardial 2014)
Failure Trial (TAC-HFT) Double-Blinded, injection is safe
Placebo-
Controlled
Autologous Stem Cells for Cardiac 30 participants Randomized Safe, improves NCT00203203 (Perin et al., 2011)
Angiogenesis (FOCUS HF) Controlled Single quality of life and
Blind Trial coronary perfusion
Randomized Clinical Trial of 30 participants Phase 1 Completed NCT01739777
Intravenous Infusion Umbilical Cord Randomized-
Mesenchymal Stem Cells on Double Blind
Cardiopathy (RIMECARD)
Efficacy and Safety of Allogeneic 600 participants Double-blind, Ongoing NCT02032004
Mesenchymal Precursor Cells Randomized,
(Rexlemestrocel-L) for the Treatment of Sham-procedure-
Heart Failure. (DREAM HF-1) controlled,

Study title Patient Phase Results Trial Citations
Enrolled Identifier
Combination of Mesenchymal and C- 144 participants Phase II, Ongoing NCT02501811
kit+ Cardiac Stem Cells as Regenerative Randomized,
Therapy for Heart Failure Placebo-
(CONCERT-HF) Controlled
Intravenous Administration of 45 participants Randomized Ongoing NCT02408432
Allogeneic Bone Marrow Derived
Multipotent Mesenchymal Stromal
Cells (MSCs) in Patients With Recent
Onset Anthracycline-Associated
Cardiomyopathy
A Randomized Clinical Trial of 27 participants Randomized Transendocardial NCT00426868
Adipose-derived Stem Cells in injection of ADRCs
Treatment of Non Revascularizable is safe and feasible
Ischemic Myocardium
CSCC_ASC Therapy in Patients 10 participants Single Group Ongoing NCT02387723
With Severe Heart Failure Assignment
Stem Cell Therapy in IschEmic Non- 138 participants Randomized Ongoing NCT02673164
treatable Cardiac Disease (SCIENCE)
Safety and Efficacy of Autologous 315 participants Randomized Ongoing NCT01768702
Cardiopoietic Cells for Treatment of
Ischemic Heart Failure. (CHART-1)
www.clinicaltrials.gov

In a small trial of allogeneic MSCs, the early results are quite

satisfactory with an increase in LVEF and no adverse effects. Another
ongoing trial known as CONCERT-HF trial uses a combination of MSCs
and c-kit+ cardiac stem cell to treat cardiac ischemia and it uses autologous
MSCs interestingly. Initial trials focused on autologous MSCs, but now
scientists are using allogeneic MSCs because allogeneic MSCs can be
obtained from younger subjects that contains more regenerative potential
based upon Bioinformatics analysis and protein expression (Pandey et al.,
2011). Moreover, using allogeneic MSCs can be cost efficient and readily
available for use (Hare et al., 2017; Perin et al., 2011; Heldman et al.,
2014). Recent trials showed allogeneic MSCs are safe and effective as
compared to autologous MSCs (Kamdar et al., 2013). Moreover, young
donor MSCs have different signaling pathways as compared to older donor
MSCs due to changing cellular dynamics of aged MSCs (Lenzen et al.,
2005; Pandey et al., 2011). The Dream-HF trial uses allogeneic precursor
MSCs to evaluate their safety for treatment of chronic heart failure.
CONCLUSION
MSCs are considered as a model candidate for regenerative medicine

because of their paracrine signaling and ability to differentiate into many
cell lines. Through paracrine signaling they modulate tissue remodeling
and angiogenesis by releasing certain cofactors that promote endogenous
cell repair. MSCs are safe and efficient as proved in many pre-clinical
trials, but there are some complications as efficient delivery methods and
viability of MSCs at the site of damage that refrain them to be used as a
fully approved therapeutic option. Investigators are working on delivery
systems more effective like, cellular scaffolds and biomaterials that can
assure the maximum number of MSCs engraftment at the site of infarct.
Although we know so much about MSCs but their actual repair mechanism
is still unknown which needs to be identified in order to use MSCs as
regenerative medicine in cardiomyopathies to their full potential.

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Mesenchymal Stem Cells As Targeted Drug

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In: Advances in Medicine and Biology ISBN: 978-1-53614-722-3

Editor: Leon V. Berhardt © 2019 Nova Science Publishers, Inc.

MESENCHYMAL STEM CELLS IN

Muhammad Shareef Masoud 1, , PhD, Uzair Ahmed1,

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Cardiovascular diseases are the main reason behind most of the

Keywords: Mesenchymal stem cells, myocardial ischemia, exosomes,

Cardiovascular diseases have become a major cause of deaths in the

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of a vessel, which leads to necrosis of heart tissue and gradually cause

CURRENT TREATMENT OF HEART DISEASES

Despite of most common disease having large death rate, heart

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2013)(Kamdar et al., 2013). Cardiac transplant, which is very expensive, is