EXPLAIN IN DETAIL THE CURRENT CONCEPT OF STEM CELL THERAPY FOR SPINAL CORD INJURY ?
A 11INTRODUCTION
1 Spinal cord injury (SCI) is a catastrophic disaster which can result in irreversible severe disability including motor and sensory loss.
2 A recent review of SCI shows an incidence of average 29.5 cases per million per year and more than one million patients suffer from paralysis caused by SCI.
3 As a result, severe disability and medical costs has become a burden to the patients with SCI, their families and community.
4 The primary causes of SCI by trauma are motor vehicle accidents, falls, violence, sports injuries, and industry-related injuries.
5 Most of the SCI patients are young men and the highest incidence of SCI is to individuals in the age range of 20 to 29
6 Over the past decades, numerous treatments including medication, surgery, and rehabilitation therapy for SCI have been performed, but there were no sovereign treatment options for chronic SCI.
7 After SCI, various unfavorable environments for recovery including release of inhibitory molecules and glial scar formation were reported ( vv imp ) - STIMULATION IS THE KEY - SO , STEM CELL THERAPY IS USED
PATHOPHYSIOLOGY
1 SCI is classified primary and secondary injury.
A ) Primary injury is caused by various external forces such as compression, contusion, or laceration.
1 The most common types of SCI are contusion of the spinal cord by a burst fracture of fracture-dislocation of the spinal column.
B ) Secondary injury is series of chain reaction which caused by the primary injury and these events occur from a few minutes to several weeks after SCI.
1 Immediately following injury, cascade events including -
A ) edema
B ) decreased blood flow
C ) vasospasm
D ) free radical production
E ) inflammation
F ) excitotoxicity
G ) lipid peroxidation, and
H ) ischemia provoke cell apoptosis.
2 Astrocytes also contribute to glial scar for-mation and these glial scarring not only prevent inflammatory cells infiltration but also interfere axon regenera-tion.
3 Moreover, tissue loss forms a fluid-filled cavity in which inhibitory molecules are upregulated and these result in a physical barrier to neuroregeneration.
So , STEM CELL TREATMENT IS RECOMMENDED TO PREVENT SECONDARY INJURY
CHARACTERISTICS OF STEM CELLS
1 Two important features of stem cells are -
A ) differentiation capability to differentiate into various cell types and
B ) renewing ability
C ) Additionally, stem cells secrete substances such as cytokine, growth factor, and trophic factor which promote neuroprotection.
ADVANTAGES OF STEM CELLS
offers potential mechanisms such as -
A ) replacement of neuronal cells
B ) remyelination of axons
C ) preservation of glial cells, and increased trophic molecules.
D ) also have ability of angiogenesis, bridging of cavities, reducing inflammation, and stimulation of endogenous precursor cells for neuronal plasticity.
CURRENT CONCEPTS
It includes -
1 Proper timing of injection of stem cells -
TIMING OF STEM CELL TRANSPLANTATION *
Useful only in acute phase ( as early as possible - preferrably within 7 days of injury
2 Administration route - intrathecal , intramedullarly , IV , IM
Intrathecal , Intramedullary being preferred owing to targetted means of treatment
3 Type of stem cells -
1 Embryonic stem cells are pluripotent stem cells because of the ability to differentiate into three germ layers and
2 adult stem cells are multipotent stem cells because of the more limited ability to differentiate - bone marrow derived mesenchymal stem cells
3 Schwann cells
4 Olfactory ensheating cells
4 Level of injury / trauma
5 Implementation of Appropriate ADL scales of functional independence such as -
A ) Katz Index of Independence in ADL
B ) functional independence measure
C ) quadriplegia index of function
D ) and modified Barthel Index
6 Implementation of Electrophysiological studies - somatosensory evoked potentials , motor evoked potentials - used as a measurement for neurological improvement, and showed the relevance to the neurological outcome.
7 Implementation of MRI studies - imaging before and after stem cell therapy to evaluate a change caused by treatment.
PROBLEMS ENCOUNTERED
1 SCI is very heterogeneous in cause and severity, and design of randomized control trials is also complicated.
2 Second, comparison between treatment and control group is probably impossible because of ethical aspects vv imp
3 At last, in terms of safety and efficacy, the result of animal experiments cannot be applied to the human directly.