STEM CELL THERAPY

FOR HEART REPAIR

Prem Sinjali
School of Health And Allied Sciences
Pokhara University
Dhungepatan-Pokhara, Kaski, Nepal.
 Contents
• Stem cell introduction
• Types of stem cells
• Induced Pluripotent stem Cells
• Why stem cell therapy for heart repair?
• Procedure of Stem Cell Therapy
• Mechanism of action of stem cells.
• Therapeutic outcomes
• Advantages
• Risks and Disadvantages
• References
 STEM CELL
Stem cells are cells with the potential to develop into
many different types of cells in the body.
 Types of Stem Cells
1. On the basis of differentiation

●
Type of cell ●
Ability to make ●
Examples in
cell types Human
1. Totipotent cell ●
All cell types in body ●
Zygote (only)
and cell types that are
important for
development of embryo
e.g. Placenta

2. Pluripotent cell ●
All cell types in body ●
Embryonic stem cell
(cell from inner cell
mass of blastocyst)
●
Induced Pluripotent
Stem Cell(IPSCs)
●
3. Multipotent cell ●
Members of a group of ●
Haematopoietic cell,
cell types Mesenchymal stem cell

●
4. Unipotent cell ●
Only one cell type ●
Muscle stem cell
 2. On the basis of Source of Origin
• Embryonic
(Embryonic Stem Cells, Embryonic Germ Cells)

• Fetal Stem Cells

(Umbilical cord, Placenta, Amniotic fluid)
• Adult Stem Cells
– Bone marrow (Haematopoietic cells,
Mesenchymal cells)
– Tissue: neural, skin, Skeletal muscle(satellite
cells), endothelial progenitors (EPCs)
 Induced Pluripotent Stem cells

• The iPSC technology was pioneered by Shinya

Yamanaka and Kazutoshi Takahashi in Kyoto,
Japan.
• Introduction of four specific genes (named Myc,
Oct3/4, Sox2 and Klf4), collectively known as
Yamanaka factors, encoding transcription
factors could convert somatic cells into
pluripotent stem cells. This type of pluripotent
cell known as IPSCs
Nobel Prize in Physiology or Medicine (2012)

Shinya Yamanaka

Kazutoshi Takahashi
Why stem cell therapy for heart
repair?
• Regenerative therapies are of major interest in
cardiovascular medicine.
• Most cardiovascular diseases, including ischemic
heart disease and cardiomyopathy, are associated
with loss of functional cardio myocytes and in
other diseases, such as sick sinus syndrome,
specific cardiac cell properties are missing.
• Unlike the Hydra or the human liver, the heart does
not have the ability to regenerate itself
spontaneously once damaged.
• Cardiomyocytes are terminally differentiated and
have a limited proliferative capacity.
• Lost cardiomyocytes are replaced by fibroblasts
and connective tissue with the remaining
cardiomyocytes becoming hypertrophic, which
may eventually lead to heart failure.
• The goal of stem cell-based regenerative medicine
in cardiovascular disease, therefore, is to create
healthy, functional cardiac cells that are able to
integrate in the injured heart and restore its
function.
 Procedure of Stem Cell Therapy for
Heart repair.
1. From Bone marrow (Mesenchymal
cells)

Step 1: Stem cell harvesting

• A small amount of bone marrow is extracted from
hip bone. In some trials, the fatty tissue from
your abdomen is used for this purpose. Local
anaesthesia are given to ensure a pain-free
experience. This step only takes a couple of
hours.
Step 2: Stem cell preparation
• The stem cells are separated from the bone
marrow or adipose tissue using a procedure
called ‘Density Gradient Technique.’ This is
done in a stem cell laboratory. This part takes
three to four hours, and a concentrated solution
of stem cells is created.

Step 3: Stem cell transplantation

• The prepared stem cells are now transplanted into
body. More commonly, the stem cells are
directly injected into the damaged heart tissue
with the help of Cather based procedure.
2. From Induced pluripotent stem
cells
Mechanism of action of stem cells
• Exogenous stem cells may also stimulate
proliferation of endogenous cardiac precursors of
stem cells through Neovascularization and
Paracrine signalling effect.
• Paracrine Effect: In this mechanism some of
specialised donor cells act to stimulate the
patient’s cells to repair diseased tissues, without
the donor cells contributing directly to the new
tissue. This happens because the donor cells
secrete factors that signal the patient’s cell to
change their behaviour and this signalling from
one cell to another is called Paracrine effect.
• Similarly, the formation of new blood vessels and
immunmodulatory effects are stimulated by
paracrine signalling of SCs
• Biologically active molecules like transforming
growth factor (TGF)-β, vascular endothelial
growth factor (VEGF), stromal cell-derived
factor (SDF)-1 and epidermal growth factor
(EGF) can be secreted by transplanted stem and
progenitor cells into the intestinal space or
bloodstream. Thus, the release of such
cytokines or extracellular vesicles is a systemic
event that promotes various regenerative
processes, e.g. Neovascularization, reduced
apoptosis of endogenous cardiomyocytes,
activation of tissue intrinsic progenitor cells
• Neovascularization is the process of development
of blood vessels, especially in tissues where
blood circulation has been impaired by trauma or
diseases.
• MSCs from different sources are capable to release
pro-angiogenic factors contributing to the
formation of new blood vessels. SCs secrete
VEGF, HGF(hepatocytes growth factors) and
IGF-1 in vitro and increased the capillary density
in the infarct border zone. Since direct
endothelial differentiation of injected SCs was
very low (< 1%), so that the improved
neovascularization was mainly stimulated by the
paracrine release of cytokines.
• Immuomodulation: They secrete various cytokines
such as epidermal growth factor through the
paracrine pathway for cardiac repair and regulate
the expression of immune cells and related
inflammatory cells to alleviate the inflammatory
response after myocardial injury. Therefore,
MSCs play a role in protecting cardiac function
and treating cardiovascular diseases
• The chemokines of MSCs are mainly CXC
chemokine receptor 3 (CXCR3) and CC
chemokine receptor 5 (CCR5) ligands, as well
as CXC chemokine ligand 9 (CXCR9), CXC
chemokine ligand 10 (CXCR10), and CXC
chemokine ligand 11(CXCR11). They are well-
known immune cell chemotactic agents capable
of modulating immune cells, such as T
lymphocytes (T cells). MSCs regulate the
immune response by regulating the activity of T
cells and B –lymphocytes (B cells), thus
inhibiting cell apoptosis.
 Therapeutic outcomes

• Improvement in heart function.

• Tissue repair and regeneration.
• Improvement in blood flow to the heart.
• Reduced fibrosis and scar size.
• Improved perfusion
• Improved Ventricular geometry
• Augmented of systolic and diastolic function
 Advantages
• Low rejection of adult stem cells
• Not immunogenic (if recipient receive their own
stem cells) Can be transformed into pluripotent
stem cell Avoid surgery and its many
complications and risks
• Treatment in cellular level
• Minimal post procedural recovery time
• No communicable disease transmission
• Easily availability as compared to donor organ
•
•
 Risks and Disadvantages
• Highly invasive procedure except for IV infusion.
• Susceptible to re- entrant arrhythmias
• Risk of propagating genetic defects
• Tumorgenecity
• Infection at the site of injection Low engraftment
Possibility of rejection if donor cells are used
• Ethical and moral issues(ESCs)
• Highly expensive treatment
• No specific markers
 References
1.Du Pré, B. C., Doevendans, P. A., & van Laake, L.
W. (2013). Stem cells for cardiac repair: an
introduction. Journal of geriatric cardiology : JGC,
vol. 10(2), page no 186–197.
2.Boyle, A. J., McNiece, I. K., & Hare, J. M. (2010).
Mesenchymal stem cell therapy for cardiac repair.
Methods in molecular biology (Clifton, N.J.), vol.
660, page no 65–84.
3.Mingliang, R., Bo, Z., & Zhengguo, W. (2011).
Stem cells for cardiac repair: status, mechanisms, and
new strategies. Stem cells international, 2011,
310928.