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Stem Cell Therapy in Neurological Disorders :

Rationale, Technique and Early Clinical Experience

Dr. dr. Asra Al Fauzi, SE, SpBS(K), FICS, IFAANS


Department of Neurosurgery – Surabaya Neuroscience Institute
Stem Cell Research Center – Surabaya Regenerative Medicine Center
Airlangga University School of Medicine-Soetomo General Hospital, Surabaya
Hemorrhagic Stroke

Stroke Infarction

Traumatic Brain Injury


Hypoxic Ischemic
Encephalopathy
Different etiologies,
and mechanisms

Neurodegenerative
Disease

Cardiac Arrest
Hypovolemic
Shock Cerebral Palsy
Stroke ICH….Post Op ?
Stem Cell

A stem cell is a ‘blank’ cell / precursor cell that has the


ability to continuously divide and differentiate (develop)
into various other kind(s) of cells/tissues

A stem cell is essentially the building block of the


human body
Fundamental Axiom in Neuroscience
“The adult human brain, in contrast to other organs
such as kidney, liver, bone and skin, lacked the
capacity for self-repair and regeneration”
Stem Cell Therapy & Mechanism of
Actions

• Replacement of degenerating or injured neural


cells
• Secretion of neurotrophic factors
• Delivery of deficient factors (gene,
neurotransmitter)
Paracrine Effect of
Cultured Mesenchymal Stem Cell

(Meirelles et al., 2009)


Cellular Therapy in CNS Disease
Another Stem Cell Victory -
Parkinson's Disease

• A degenerative disorder of the


central nervous system

• Sufferers lack a sufficient amount of


a brain chemical called dopamine

• The cure of this disease is to multiply


cells that release dopamine
Adult Neurogenesis : Role of Neurogenic Niches
(SVZ)
Route & Site of Delivery

• Direct Implantation : Intracerebral and


Intraventricular

• Systemic Implantation : Intravenous, Intra-


arterial or Intraperitoneal

Benefit and Effectiveness !!


Timing

• Acute phase : neuropr0tective mechanism,


acute delivery of cells will be critical
• Sub acute phase : endogenous repair
mechanisms ( brain plasticity, angiogenesis,
neurogenesis), delivery after three weeks
• Chronic phase : to promote adult endogenous
neurogenesis , delivery after several months
STEM CELL THERAPY

Replacement Therapy / to Replace

Parakrin Effect / to Stimulate


• Neuroprotektif agent
• stimulate angiogenesis
• imunomodulator
• Enhance Neuroplastisity
(Kondziolka et al., 2002; Wuk Jeung et al., 2003; Tae Lee et al., 2008)
Direct Intraventricular Transplantation
via Ommaya Reservoir
Total : 37 patients

• Stroke : 19
• Cerebral Palsy : 5
• Spinocerebellar Atrophy : 5
• Severe Parkinson :4
• Head Injury : 2
• CNS infection : 1
• Creutzfeld-Jacob ds : 1
Neurotransplantasi Stem Cell

2016 AANS
International Visiting
Surgeon Award
Result
Outcome *) Complications/side effects

• 14 patients improved • ICH post procedure (1)

• 2 patients no follow up • Cardiac arrest during


procedure (1)
• 1 patient worsening
• Shivering (1)
• No mortality
*) NIHSS, Bartel Index (BI), modified • Febris post procedure (2)
Rankin Scale (mRS) • Transient cephalgia (2)
CVA hemorrhagic case
Cell Transplantation in CNS
disease
• Widespread damage : cell transplant may need to
initially immature and phenotypically plastic to
differentiate into appropriate cell type depending on
the ectopic site.
• Timing of transplantation : theoritically depends on
the purpose and goal of therapy
• Route and site of delivery : the optimal approach
depends on the cell type, risk & efficiency, and the
mechanism of action
• In vivo monitoring of repair progress : PET scan,
Functional MRI, Biomarkers…..???
Various Cell Types

• Neural stem/progenitor cells (NPCs) cultured from


fetal tissue

• Immortalized neural cell lines

• Hematopoietic/endothelial progenitors and


mesenchymal cells isolated from bone marrow,
umbilical cord, peripheral blood or adipose tissue
Suitable Cells for Transplantation
• a reliable and readily available source of cells. The cells
should be proliferative to allow for ex vivo production of high
numbers
• there should be adequate differentiation into all desired cell
types
• once transplanted, the cells should localize to sites of injury
to exert a functional effect
• transplanted cells should remain viable, not be rejected by
the immune system
• transplants should pose no untoward effects such as tumor
formation or seizures
Stem Cell Source

• Bone Marrow • Articular Cartilage

• Trabecular Bone • Skin

• Muscle • Peripheral Blood

• Adipose • Deciduous Teeth

• Periosteum • Periodental Ligament

• Synovial membrane
Conclusions

• Cell transplantation therapy for neurological diseases holds the


great promise.

• However, many fundamental questions related to the optimal


candidate, the best cell type, the number and concentration of
cells, the timing of transplantation, the route and site of delivery,
and the need for immunosuppression remain to be answered.
Conclusions
Clearly, more research is needed to
answer many questions. Collaboration
between neuroscientists,
neurosurgeons, neurologists and other
related physicians is required to
translate cell transplantation therapy
to the routine and safe clinical
practices.
..the unthinkable may soon be possible..
The future of Neurological Treatment..??
Acknowledgements
• Prof. Dr.dr.Nasronudin,SpPD
• Prof. Fedik A. Rantam, MD,PhD
• Prof. Dr.dr.A. Hafid Bajamal,SpBS
• Prof. Dr.dr. Moh. Hasan Machfoed,SpS
• Prof. Dr.dr.David Perdanakusuma,SpBP
• Dr.dr.Ferdiansyah,SpOT
• Dr.dr.Heri Suroto,SpOT
• Dr.dr.Joni Wahyuhadi,SpBS
• Dr.dr. Purwati,SpPD
• Dr.dr. Soni Wibisono,SpPD
• Dr.dr. Ugroseno,SpPD