REGENERATIVE MEDICINE

IRAWAN YUSUF
Faculty of Medicine Hasanuddin University

INTRODUCTION
Diseased, degenerating or damaged organs and
tissues give rise to a wide range of chronic illnesses.
Patients suffering from such illnesses are currently
faced with a relatively short list of options, include:
long-term drug therapy, which may allow a disease to be
managed but rarely cures it;
organ transplant (there is a shortage of donor organs);
medical devices such as pacemakers.

INTRODUCTION
Regenerative medicine aims to restore the function of tissues and
organs by a variety of approaches.
The idea is not new; the first bone marrow transplant took place in
1956, to treat a young boy suffering from leukaemia.
In the 1956, bone marrow transplant from the patients identical
twin.
By the late 1960s and early 1970s, they were able to match donor
tissues to patients by tissue typing.
Much of the recent interest in regenerative medicine arises from
developments in stem cell research, but there are also promising
possibilities in biomedical and tissue-engineering.

THE GOAL
To create products that improve tissue function or heal
tissue defects.
Replace diseased or damaged tissue
Because
Donor tissues and organs are in short supply
We want to minimize immune system response by
using our own cells or novel ways to protect
transplant.

Regenerate, repair and replace

Regenerate
Identify the cues that allow for regeneration without
scarring
Like growing a new limb

Repair
Stimulate the tissue at a cell or molecular level, even at
level of DNA, to repair itself.

Replace
A biological substitute is created in the lab that can be
implanted to replace the tissue or organ of interest

TYPES OF REGENERATIVE MEDICINE

Cell Therapies:
Therapy using a patients own cells
Therapy using cells from another person

Tissue Engineering.
Biomedical Engineering.
Gene Therapy.

Cell-based therapies
Aimed at certain diseases
Uses mostly only cells and no materials
Type I diabetes transplant of new pancreas cells
Adult stem cells for heart disease
Neuronal transplants for Parkinsons disease
Bone marrow transplant for various blood cancers
Muscular dystrophy and polio

Tissue Engineering
Tissue engineering involves modifying cells or tissues in
some way so that they can repair, regenerate or replace
tissue in the body.
Using well designed scaffolds and optimized cell
growth, we can create tissues such as:
Skin
Bone
Cartilage
Intestine

These have been successfully engineered to some extent

Tissue-engineered products contain

mixtures of the following:
Biological components - cells
Can be genetically modified to behave a
specific way
Chemicals
that tell the tissue to regenerate

Biomedical Engineering
Biomedical devices that mimic the function of a
tissue or organ.
A non-biological component
Polymer scaffold
Fibers, plastic, other natural components

Gels

CELL THERAPY FOR

CARDIOVASCULAR DISEASES
Coronary artery diseases:
Refractory angina (Baxter CD 34+;
Acute myocardial infarction with left ventricular
dysfunction;
Heart failure.

Ischemic stroke.
Non-ischemic cardiomyopathy.

CELL THERAPY FOR

CARDIOVASCULAR DISEASES
In patients with refractory ischemia, the goal is to improve coronary
blood flow by promoting angiogenesis. The largest experience is with
circulating CD34+ cells, and study is ongoing with intramyocardial
delivered BM mononuclear cells (BMNCs) into the ischemic zone.
In patients with acute MI, trials have utilized intracoronary delivery of
BMNCs with considerable variability in the number of cells and the
timing of delivery as well as the measurement of the primary endpoint.
In patients with coronary heart failure (CHF) following MI, the goal is
to promote myogenesis, utilizing skeletal myoblasts delivered into the
previously infarcted zone.
For peripheral arterial disease, studies are focusing on claudication and
critical limb ischemia (CLI).

Possible routes for cell therapy to the

heart
CFX

Strauer BE, Kornowski R. Circulation 2003;107:929-34.

EPC number has prognostic

importance
N = 519 males with CAD, mean
age 66 y
1.00

Group 3 (high EPC level)

0.98

Event-free
survival

0.96

Group 2 (medium EPC level)

0.94

Group 1 (low EPC level)

0.92
0.90
0
0

100

200

300

365

Days
Werner N et al. N Engl J Med. 2005;353:999-1007.

Open label non-randomised trial

BMC group
Control group

Cells
Control

100%
98%

p<0,01

99%
96%

SURVIVAL
98%
90%

96%
84%
Year

Endsystolic volume (ml)

Control

118

BMNCs safely produced a sustained benefit

on clinical outcome and LV performance not
observed before

BMCs
132

128
123

120
110

112

Largest trial (391 pts) comparing BMNCs vs

conventional therapy in patients with heart
failure due to healed infarction. Simple
method of delivery. Largest (60 moths)
follow-up. Comprehensive assessment

111

This STAR sheds light on the mechanisms of

LV benefit of cell therapy

Cardiac & Endothelial (Taylor D. Nature Med 2008)

Bone marrow cells promote myocardial

regeneration: Postulated mechanism
Transplanted
Cells

Infarcted
myocardium
Unknown molecular
signal(s)

Cell migration to damaged

area
Proliferation and
differentiation
Cytoplasmic
proteins
Cardian myosin
-Sarcomeric actin
Connexin 43

Nuclear
proteins

Csx/Nkx2.5
MEF2
GATA-4

Functional
competence
Orlic D et al. Nature. 2001;410:701-5.

SEVERAL ISSUES
Research issue:
Human resources;
Infrastructure;
Funding.

Clinical trial issues:

Patient safety;
Cost.

Regulatory issues
Innovation vs patient safety.

CONCLUSIONS
Regenerative medicine includes approaches such as cell
therapy, tissue engineering, gene therapy and biomedical
engineering, that aim to restore the function of diseased
or damaged tissues and organs.
It has the potential to deliver benefits to patients across a
wide range of conditions.
Regulation of regenerative medicine requires a balance
between protecting patients on the one hand and
encouraging innovation on the other hand.