Stem CellBased Therapies for

Spinal Cord Injury

Created by :
Rishi S., Nandoe Tewarie, Andres Hurtado, Ronald
H. Bartels, Andre Grotenhuis, Martin Oudega

1
 STEM CELL
A class of undifferentiated
cells that are capable to
differentiate into specialized
cell types
Totipoten Differentiates into any cell
t type without exception.

Differentiates into any cell

Pluripote type present within a germ
nt layer

Multipote Differentiates into cells of a

particular cell lineage (in a
nt germ layer)

Differentiates into only 1

Unipotent type of cell
 Transdifferentiation
- Change of cells fate (cell enters a lineage
that was not the original destination).

- Forced differentiation cell from a lineage

within an unnatural germ layer induced
carciogenesis
INDUCED PLURIPOTENT STEM CELLS

Stem cells which resemble

pluripotent embryonic stem cells
derived from mature,
differentiated cells of the body
that have been reprogrammed
through genetic manipulation and
other techniques to restore
developmental potential
INDUCED PLURIPOTENT STEM CELLS

obtain pluripotent cells by reprogramming

differentiated cells, such as fibroblasts

4 transcription factors ; OCT3/4 (octamer-4),

SOX2 (sex determining region Ybox2), KLF4
(Kruppel-like factor), and MYC (induced
pluripotent stem (iPS) cells

The underlying mechanisms and

reprogramming procedure are still unknown
 ..\StemCellShorts
- Stem cells animation part
s 1, 2 & 3.mp4
 Spinal Cord Injury
An insult to the spinal cord resulting in
a change, in the normal motor,
sensory or autonomic function. These
change either temporary or
permanent.
 Endogenous Regenerative
Schwan cells migrate from spinal
roots into the damaged tissue and
myelinate spinal cord axon
The expression of regeneration-
associated gene is increased in
damaged neurons
There is a surge in proliferation of
local adult stem cells and progenitor
cells
 Endogenous Regenerative
Axonal growth is twarted by growth
inhibitors on oligodendrocyte myelin
debris on cells that from scar tissue
Newborn stem cell and progenitors
do not integrate functionally into the
injured spinal cord tissue
Potential Stem Cell for SCI
 Axon Regeneration
Secrete
Neural neurotropic
factors lead
progenitor promote growth
cells of damaged
axons

preventing
stem celllike axons from
olfactory recognizing
ensheathing growth
inhibitory
cells molecules
Neuroprotection

Neural progenitor cells

protect against excitotoxicity
protect neural cells from death mechanisms

Bone marrow stromal cells

Secrete growth factors
 Cell Replacement in The Injured
Spinal Cord
Restoration of new circuits
Neuron

oligoden Able to myelinate axons

drocyte

Astrocyt Providing scaffolding and nutrition of the injured area

e

differentiate into bone, fat, tendon, and cartilage cells.

Mesenchym transdifferentiate into liver, skeletal, and cardiac muscle, cells
al stem
cells and into central nervous system cells
 CLINICAL APPLICATION TO
SCI

Autologous bone marrowderived stem cells have

been transplanted in the injured spinal cords of
25 patients in Guayaquil, Ecuador
Result : improved walking and sensory
perception
 STUDY 1

In a study with human participants in China,

tested the transplantation of SCs in 6 patients
and observed the results for over 5 years, At
the end of the study, they reported autonomic,
sensory, and motor improvement in all
patients. MRI scans revealed that the
myelomalacia and cystic degeneration had also
been reduced.
 STUDY 2

Saberi et al. aimed to evaluate the safety and

feasibility of SC transplantation. In both studies,
there were no significant changes in patients
MRI scans, and they reported neither
neurological worsening nor improvement. They
only reported autonomic functional recovery and
improved quality of life
 STUDY 3

In 2006, Moviglia et al. reported a combined treatment

with MSCs and autoimmune T (AT) cells with 2 spinal cord
injury patients. The main goal behind this approach is to
control inflammatory activity in order to create the ideal
microenvironment for cell transplantation, as it has been
shown that AT cells are essential for tissue repair. Both
patients reported motor improvement and no adverse
effects.
 STUDY 4

Saito et al. described a single patient who had a fracture-

dislocation at C5 and reported loss of sensation and
movement below the lesion site. The investigators
transplanted autologous BMSCs by lumbar puncture 13
days after injury and evaluated the patient for 6 months.
They were able to evidence some motor and sensory
improvement (relative to pre-transplantation scores) after
1-3 months; after 6 months, they observed a slight motor
improvement with no further sensory improvement.
 STUDY 5

Matsuda et al. Reported tumor formation 21

days after transplantation with ESCs, when all
behavioral improvements had ceased. They
were then able to suppress tumorigenesis in a
culture with bone marrow stromal cells (bmsc).
 Embriyonic Stem cell
Advantage Disadvantage

Isolated from induce teratomas

blastocyst stage may undergo genomic
embryos, somatic cell and epigenetic
nuclear transfer or changes that could
parthenogenetic lead to transformation
activation of eggs prone to be rejected
after injection into
do not undergo adult tissue
senescence long-term treatment
with
high telomerase immunosuppressive
activity drugs may be
required
 adult stem cells
Disadvanta
Advantage
ge
can be transplanted without
less plastic than ESCs and divide
genetic modifications or
less frequently in culture
pretreatments
differentiation potential may
Immune rejection (-)
decrease in time

a high degree of genomic stability

during culture

usually do not result in tumor

formation

much less moral concern

surrounding the use
 ETHICAL AND SOCIAL
CONCERNS
ESC

According to the Roman Catholic Church

and other religious institutions, an
embryo must be treated from
conception as a living person. This
implies that a blastocyst cannot be used
to harvest cells.
 Adult stem cells

oocytes can be derived from stem cells of male

origin, which allows the production of a child from
one or two male biological parents. The potential
biological problems and psychological effects on the
child are unknown. It would also be possible that
the offspring develops defects because of
acquisition of pairs of (recessive) genes .
 Conclusion
stem cellbased therapies are at an early
stage, and the associated risks are still
unclear

Stem cells hold promise for spinal cord

repair, but their true potential has not yet
clearly been shown

Stem cells tendency to generate tumors

is still unknown
THANK YOU