Tissue engineering in SCI.

1. Tissue Engineering in the
Repair of Spinal Cord Injury
M.Vharshini
Department of Biomedical Sciences
Sri Ramachandra University

2. THANK YOU

4. INTRODUCTION
• Spinal cord injury (SCI) may lead to a devastating and
permanent loss of neurological function that significally
affects the mobility and quality of life in adults (
Average age of patient is 38 years old ).
• SCI is a complex set of damaging events that occur at
the the cellular level and it can be divided into four
main stages, they are
• The immediate
• Acute Stage
• Intermediate
• Chronic Phase

5. • Clinically, the treatment of SCI mainly focuses on
reducing secondary damage and prevention of
further complications.
• To successfully repair the SCI and promote functional
recovery, the following must be achieved.
1. Reduction of the death of neuronal cells
2. Inhibition of glial scar formation, since glial scaring
decreases axon growth
3. Provision of matrix at the injury site to supply the nutrients
required to support axonal growth
4. Elimination of immune reactions
5. Facilitation of the build-up of functional synapses and the
transmission of neurotransmitters by regenerating axons.

6. TISSUE ENGINEERING IN THE
REPAIR OF SCI
• Tissue engineering is a promising method
that may be used for the treatment of SCI.
• It involves three factors:
1)The Seed Cell,
2)Scaffold,
3)Growth factors
• For repair strategy to be successful, the
selection of an appropriate seed cell,
scaffold and growth factor is required.

7. Factors of Tissue Engineering in
SCI

8. SEED CELL
In Tissue Engineering Seed Cells must meet
the following criteria:
• Successful ability to proliferation in vitro
• Good cell viability and function
• High level of purity
• No rejection by the immune system and
• High safety

9. • Embryonic Stem Cell and Neural Stem Cells are
the most important types of stems cells that
were used in the early stages of seed cell
research.
• Transplanting ES Cells into the brains was
shown to significantly improve neurological
function in an animal model of Parkinsons’
disease.
• The main reason for the success is that cells
survived and were differentiated into different
cells, such as Oligodendrocytes, Astrocytes
and Neurons

10. Differentiation of ESCs

11. NEURAL DIFFERENTIATION OF
EMBRYONIC STEM CELL
• This method has certain ethical issues
and problems with regard to rejection
reactions.
• In addition the availability of neural stem
cells is limited and therefore their
widespread clinical use is not viable.

12. SCHWANN CELLS:
• Schwann Cells originating from dorsal
and central roots are one of the cellular
components that migrate to the site of
issue damage after spinal cord injury.
NEURAL STEM PROGENITOR CELLS:
• A scaffold seeded with NSCs for repairing
CNS lesions can provide a platform for
the cells enabling repair of large neural
defects.

13. Stem Cells Treatment for SCI

14. BONE MARROW STEM CELLS:
• With advances in stem cell research Mesenchymal Stem
Cells (MSCs) extracted from Bone Marrow (BMSCs)
have been shown to contain pluripotent precursor cells,
which have the ability to differentiate into various types
of brain cell.
• In vivo transplantation of BMSCs into the brain has
established that they migrate throughout various brain
regions where they undergo differentiation into cells
with astrocytic and neuronal phenotypes.
• If BMSCs are to be used clinically, the extraction of
bone marrow from patients is necessary which result in
Pateint Trauma. Therefore, on increasing number of
studies have suggested the use of adult stem cells.

15. ADULT STEM CELLS – ADIPOSE
DERIVED STEM CELLS
• Adipose derived stem cells (ADSCs) is the most
suitable type of adult stem cells for use as seed
cells of SCI treatment.
• An advantage of using ADSCs is that obtaining
these cells is minimally invasive to the patient.
• If different types of induction medium are used,
the cells may differentiate in to adipocytes,
oesteoblasts, chondrocytes and neurons, a
promising tool for SCI treatment.

16. • Recent studies have shown that due to the
secretion of various growth factors such as
hepatocyte growth factor (HGF), Tumor
necrosis factor – Alpha (TNF-Alpha),
Vascular endothelial growth factors (VEGF),
Brain-derived neurotropic factor (BDNF)
and Nerve Growth Factor (NGF).
• ADSCs may be used in the acute stages of SCI
and have the potential to improve functional
recovery, tissue preservation and neurenal
regeneration.

17. SCAFFOLD
• In addition to seed cells, tissue engineering
scaffolds are also important and their potential
use in the spinal repair.
• The requirements of a scaffold for spinal cord
regeneration are as follows:
• Good bio-compatibility, in order to avoid
reactions with the immune systems
• An ideal degradation rate and the formation of
non-toxic degradation products.
• Mechanical properties that are suitable for cell
adhesion and axonal re-growth.

18. • In order to successfully use tissue
engineering to repair SCI the selection of
suitable scaffold is particularly important.
• Compared with a single component scaffold,
a mixed scaffold may be more successful as
it may minimize the disadvantages of the
single component scaffold and provide a
scaffold with increased functionality.

19. • Silk fibroin (SF) has excellent mechanical properties and
has been used as a scaffold for the treatment of SCI but the
disadvantage is that when it is dry it is brittle and difficult
to handle
• To overcome the shortcomings of SF, a blend of both
chitosan and Silk Fibroin to make silk fibroin – chitosan
(SFCS) has good mechanical properties and may be used as
a scaffold material for the repair of SCIs.
• A study by Liu et al using nanofibrous collagen nerve
conduits demonstrated that this type of scaffold is capable
of promoting neural fiber growth following SCI, and is also
capable of inhibiting glial scar hyperplasia.
• A study by Du et al demonstrated that a gelatin sponge is
more suitable that an PLGA scaffold for transplantation
into the spinal cord to promote the recovery of SCI.

20. • Comolle et al used a poly (N-isopropylacrylamide) –co-
poly (ethylene glycol) (PNIPAAM-PEG) injection
scaffold, which provided the sustained release of BDNF
and neurotrophin-3 (NT-3) for up to four weeks, the
constant secretion of these GFs was identified to be a
positive factor in functional recovery.
• Scaffolds prepared from natural components may be
more advantageous as the reaction of the immune system
and the inflammatory reaction is reduced following
implantation into the body.
• The blending of artificial and synthetic materials may
reduce the disadvantage of using synthetic material while
also avoiding the disadvantages of using solely natural
components

21. GROWTH FACTOR
• Neurotrophic factors play an important role
in the functional recovery following SCI, as they
protect neuronal cells from apoptosis and
promote axonal regeneration.
• Neurotrophic factors may be divided into:
– Neurotrophins
– Ciliary neurotrophic factor
– Glial cell line – derived neurotrophic factors
– Other growth factors or cytokines
• The most frequently used neurotrophic factors
are NGF, NT-B, and BDNF.

22. • NGF is a core factor in the regulation of peripheral
innervoctions, was found to have an effect on the
CNS
• Brain-derived neurotrophic factor
(BDNF)expresses its biological effects through the
activation and binding of TrkB.
• Stokols et al discovered that a BDNF-
incorporated agarose scaffold implanted into
the spinal cord of a rat resulted in the linear –
fashioned growth of regenerating axons through
the scaffold

23. • NT-3 which may be generated by the cloning of
a multifunctional NGF gene not only
maintains motor neurons, sympathetic neurons
and dopaminergic neuron differentiation, but
also maintains the survival of sympathetic and
sensory neurons and promotes growth of nerve
in vitro.
• NT-3 is considered to be the only gene to
promote the growth of the Corticospinal
tract (CST) following SCI.

24. CONCLUSION
• Tissue engineering is a promising method that
may be used for the treatment of SCI.
• It involves three factors: the seed cell, the
scaffold and a growth factor.
• For the repair strategy to be successful, the
selection of an appropriate seed cell, scaffold
and growth factor is required.
• In conclusion, although tissue engineering has
a promising future for the treatment of SCI,
extensive further studies are necessary for the
successful treatment of SCI to be achieved.