ROLE OF STEM CELLS IN TREATMENT OF NEUROLOGICAL AND ARTHRITIS

3. Stem cells
are undifferentiated biological cells that can differentiate into
specialized cells and can divide (through mitosis ) to produce
more stem cells. They are found in multicellular organisms .In
mammals there are two broad types of stem cells: Embryonic ;
which are isolated from the inner cell mass of blastocysts and
Adult , which are found in various tissues In adult organisms,
stem cells and progenitor cells act as a repair system for the
body, replenishing adult tissues. In a developing embryo stem
cells can differentiate into all the specialized cells—ectoderm,
endoderm and mesoderm (see induced pluripotent ste cells )—
but also maintain the normal turnover of regenerative organs,
such as blood, skin, or intestinal tissues.

4. • SCs are unspecialized cells in the human body that
are capable of becoming specialized cells with
specialized functions.
• For example: HSCs are unspecialized stem cells and
able to into blood cells; RBC, platelet &
WBC with specific function each.
• Stem cell remains uncommitted until it receives a
signal to develop. Each new cell, either become a
stem cell or another cell type with a specific
function, i.e. blood cells.

5. stem cell biology:
It is an attracted field, has a role in treatment of
incurable diseases, major classes and option
of work.
word of “ ” has been loosely used by
some scientists without the demonstration of
SC markers or confirmation of stemness via
transcriptone profiling. The correct definition
through the proper and accepted tests be
addressed before a particular cell type is
classified as stem cell

6. Fig ( )

8. Haematopiosis

9. Formation of blood cells

10. Hierarchy of stem cells

11. Classification according To potency

12. Origin of adult stem cells
• Some believe that adult stem cells and
fetal SC are evolved from embryonic SC
. Therefore the few SCs in adult are
from the remnants of original
embryonic SCs. These either develop
into an organs or remained in the cell
niches in the organs ready for repair in
the future.
• https://prezi.com/3yht9req9fs7/what-are-
stem-cells/

13. First: protocol of embryonic SC (
ESC)
Fertilized ova, zygote, 2-cells, 4-cells, 8-cells and
morula resulting from cleavage of the early
embryo are example of totipotent cells ( has
the ability to form a complete organism)
Three layers are developed : endoderm ,
mesoderm and ectoderm
Embryo should be lack of genetic & infectious
diseases

17. Fetal Stem Cells
• They are primitive cell types found in the
organ of fetuses.
• Neural crest cells, pancreatic, HSCs have been
isolated from abortuses
• Fetal neural SCs derived from fetal brain
• Fetal blood, placenta and cord are rich in HSCs

18. Cord blood stem cells

19. Characteristics of cord BSCs
-contains stem cells which are quite distinct from
bone marrow SCs
-stem cells are equal or exceeds that of bone marrow
and produce large colonies in vitro, have different
growth factors, long telomere and can be expanded
in long term culture
-shows decreased graft versus host reaction
-multipotent ( liver and neuron cells)
-can be storage for later use
-matrix of Wharton`s jelly source of MSCs which have
high c-kit marker useful for neurons

21. Filton center of stem cell and cord
blood bank

25. Types of adult stem cells
2-Mesenchymal SCs1-Haemopiotic SCs
4-Liver SCs3-Gut SCs
6-Epidermal SCs (skin ,
hair)
5-Bone & cartilage SCs
8-Pancreatic SCs7-Neuronal SCs
9-Eye SCs

27. Principles of stem cell
plasticity
There are four mechanism of differentiation of HSC:
1- differentiation: cells develop from a less
differentiated to a more differentiated states and
maintain the ability to diff into multiple cell lines
2- indirect trans-differentiation: gene expression of
HSC changes to an alternative cell type through
de re-diff.
3- direct diff : HSC ability to change gene expression
directly into other cell type
4- fusion: usually MSC fuses with other non
haematopoietic cells and gene expression of
marrow cell takes on nucleus of the latter.
However, nucleoli have not to fuse

29. Adult stem cell plasticity
examples
- Blood cells becoming neurons
- Liver cells stimulating to produce
insulin
- Haematopoietic ( blood cell
producing ) stem cells that become
heart cells

30. Clinical applications
• Stem cells, which are undifferentiated, have
many clinical and scientific uses:
- Cell based therapy ( regenerative therapy )
- Therapeutic cloning
- Gene therapy
- Cancer research

31. Potential uses of SCs in Vitro
• Biotechnology ( drug development and
discovery ) stem cells provide cell to test
new drugs
• Safety testing of new drugs on
differentiated cell lines
• screening of potential drugs to test anti
tumor cells and reduce animal testing

32. Potential uses continue..
Cell based therapies:
• Regenerative therapy to treat Alzhiemer`s,
Parkinson`s, spinal cord injury, stroke, sever burn,
heart disease, diabetes. Osteoarthritis and
rheumatoid arthritis.
• Stem cells in gene therapy as vehicles
• Stem cells in therapeutic cloning
• Stem cells in cancer

33. Stem cells for the treatment of
neurological disorders
Human neurological disorders such as Parkinson's disease,
Huntington's disease, Alzheimer's disease, multiple
sclerosis (MS), stroke, and spinal cord injury are caused by
a loss of neurons and glial cells in the brain or spinal cord.
Cell replacement therapy and gene transfer to the diseased
or injured brain have provided the basis for the
development of potentially powerful new therapeutic
strategies for a broad spectrum of human neurological
diseases.
In recent years, neurons and glial cells have successfully
been generated from stem cells such as embryonic stem

34. ability to heal after injury due to the inability of the
brain to make new cells. Researchers observed
that there are two special regions of the brain that
actually do produce new cells, even in adults. The
cells from these two special regions are called
neural stem cells and now scientists are working
hard to determine how their special properties can
be used to treat different types of damage in the
brain.

36. Autologous mesenchymal stem cells for the treatment of
secondary progressive multiple sclerosis: an open-label
phase 2a proof-of-concept study, 2012
This study applied on Patients with secondary
progressive multiple sclerosis involving the visual
pathways who were recruited from the East Anglia
and north London regions of the UK in 2012.
The study aims: the safety & feasibility of the MSCs
infusion, adverse effect of infusion 20 months before
and 10 after infusion and finally to assess the
anterior visual pathway.
Isolated, expanded, characterize and administered in
ten patients. There were no adverse effects
identifiable and there were improvement in visual
acuity, visual evoked response latency and an
increase in optic nerve area. However there were no

37. Changes in visual function, visual evoked
response amplitude and optic nerve area after
SC treatment respectivly

39. There was a study has tested a Long-Term Follow-Up of Intravenous
Autologous
Mesenchymal Stem Cell Transplantation in Patients With Ischemic Stroke
in neurology department, school of medicine in South Korea in 2010
• The study has evaluated the safety and efficacy
of i.v. MSCs transplantation in 85 patients with
sever middle cerebral artery territory infarct.
• Patients were randomly allocated to one of two
groups, those who received i.v. autologous ex
vivo cultured MSCc (MSC group) or those who
did not (control group), and followed for up to 5
years.
• Mortality of any cause, long term side effects,

40. Study protocol

41. Results of that study were depended
on clinical, biomarkers and neuro-
images
• 25% of MSCs group and 58% of control group
died during the follow up period.
• Significant side effects were not observed
following MSC treatment.
• Co morbidities occurrence did not differ between
groups.
• Modified Ranken Scale score was increased in
MSCs group whereas decreased in control
• i.v. MSC transplantation was safe.
• Clinical improvement may improve recovery after
stroke

43. The results conducted functional outcome at day 7 of
admission and last evaluation median 3.5 years
according to mRS score

44. • Patients with stroke who received MSC
infusion and the subventricular zone status
(SVZ)

45. Control group: patients with stroke
who did not receive MSC infusion

46. Stem cells therapy in joints
• Experts are researching ways to use stem cells to treat arthritis
in the knee and other joints. Many doctors already use stem
cell therapy to treat arthritis, but it is not considered standard
practice.
• Stem cells can be applied during a surgery (such as the
surgical repair of a torn knee meniscus) or delivered through
injections directly into the arthritis joint.
• When administering stem cell injections, many physicians use
medical imaging, such as ultrasound, in order to deliver cells
precisely to the site of cartilage damage.
• There is some evidence that people with severe arthritis can
benefit from stem cell therapy.1 Most research indicates that
younger patients who have relatively mild osteoarthritis or
cartilage damage see the most benefit

47. Stem cell therapy safety
• Most stem cell therapy using adult stem cells is
considered safe because the stem cells are collected
from the patient, minimizing the risk of an unwanted
reaction. The most common side effects are temporary
swelling and pain.
• Some research suggests stem cell therapy engaging in
these kinds of practices may elevate the risk of tumors.
• when applied to an arthritic joint, stem cells might:
- Develop into needed cartilage cells
- Suppress inflammation that can make arthritis worse
- Release proteins (cytokines) that slow down
cartilage degeneration and/or decrease pain

48. Candidate!!??Stem cell implantation may be
recommended for patients with osteoarthritis of the
knee. Typically these patients have failed other
treatment options including rest, medications,
other injections and physical therapy and are not
anxious for total knee replacement.
• Who is not candidate??!! Patient with a blood
borne Cancer (such as lymphoma or leukemia),
not in remission for at least 5 year
• Certain other malignancies or blood borne
diseases that you are being treated for
• Patient with any current infection
• Patient who uses a high dose of Coumadin
• Patients with multiple medical issues may not be
good candidates

51. There was a study about the role of PRP
and stem cells injection in O A patients of
knee J in 2015
• The study supplied the affected knee joint
with MSC in combination with PRP. As
they have treated 65 of cases of moderate
to sever OA of knee joint (56 to 87 years
age) and 50 other cases for control.
• the study conducted from 2012 to 2014,
control group received local steroid and
both groups were undergoing medical

52. Procedure was as below:
• Treated group were injected 7cc of PRP
mixed with 3cc of stem cell preparation in to
the select joint along with 5cc of 0.5%
preservative free bupivacaine, under strict
aseptic precautions. Sterile bandages were
applied after the injection followed by
mobilization immediately after the procedure.
• Whereas control group similar procedure is
performed in the control group with 10cc of
0.5%bupivacaine, with 60mg of

55. RESULTS: Both the groups were observed from time to
time and analyzed based on the pain scores at 3 days, 1
week, 4 weeks, 3 months and 6 months intervals.
0
10
20
30
40
50
60
70
3 days 1st week 4 weeks 3 months 6 months
tested group
control group
Column1

56. Final Results were 86%of test group had improvement in
pain and function of knee joint and 52%of control group
had improvement and pain and function of the knee
joint at the end of the 6 months.

57. So it can be concluded that:
• PRP and stem cells injections in to the
osteoarthritic knees, produces good
results and safe. If the patient is not opting
for surgical procedures and this is the only
better treatment modality for controlling
the pain and improvement of joint function.
Hence use of PRP and stem cells
injections in osteoarthritic patients is great
value in preventing the further damage of
the cartilage. By repairing the damaged
cartilage with the PRP and stem cells, pain
is greatly reduced, increase in the function