Effectiveness of Stem Cells for Cerebral Palsy


 Administrator    28 Oct 2019 : 07:05

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The growing amount of research into the effectiveness of using stem cells for cerebral palsy sufferers is tremendously positive.

The growing amount of research into the effectiveness of using stem cells for cerebral palsy sufferers is tremendously positive. In this article we’ll provide an overview of Cerebral Palsy, and why the stem cell cerebral palsy research leaves such great cause for optimism. 

Causes of Cerebral Palsy

The causes of cerebral palsy (CP) are varied but can be due to abnormal development of the brain or damage to the brain that results in a lack of oxygen known as hypoxic-ischemic encephalopathy (HIE). Encephalopathy means damage or disease of the brain. The damage can occur before birth (congenital) or after birth (acquired). Cerebral palsy primarily affects motor functioning in a wide range of severity. Lack of oxygen during pregnancy and before the labor and delivery process causes the largest proportion of cases of CP cases. Rarely does the labor and delivery process due to lack of oxygen or trauma cause CP.

Risk Factors for Cerebral Palsy

The following risk factors are associated with congenital CP such as low birth-weight (weighing less than 2500 grams or 5.5 pounds) or very low birth-weight babies( less than 1500 grams or 3.3 pounds) Low birth weight can be due to premature birth, smoking, twins or triplets delivered prematurely, intrauterine growth restriction, placental problems, and maternal diseases such as high blood pressure seizures, and diabetes.

Intrauterine infections such as bacterial or viral infections of the womb can cause CP. Babies with congenital disabilities such as hydrocephalus( water on the brain)  or microcephaly (extremely small head/brain) and bilirubin build-up can lead to kernicterus in the brain and lead to CP. Maternal-fetal blood incompatibility is one other cause for excess bilirubin build-up. The degree of hypoxia (oxygen deficit) must be very severe such that it causes acidosis (blood pH 7.0 or less)

Acquired CP occurs after 28 days after birth and is a less common cause for CP. Common causes of acquired CP are due to infections, underlying diseases or medical conditions, undiagnosed congenital disabilities, or head trauma. Infections during infancy such as meningitis or encephalitis, which infect the brain and the surrounding tissue can cause CP. Motor vehicle accidents, trauma, physical abuse, and falls can result in significant brain injury, causing CP. Likewise, hypoxia or asphyxia from drowning or smoke inhalation may result in CP. Strokes from abnormal blood vessel connections in the brain that burst can cause oxygen deprivation leading to hypoxic-ischemic encephalopathy. Heart defects that allow blood clots to travel to the brain are other hypoxic events [1-12].

HIE can result in long term neurological consequences. Twenty-three percent of babies worldwide are born with either mild, moderate, or severe HIE.

How does Cerebral Palsy affect cells?

Hypoxia is present when the oxygen level in the fetal blood circulation decreases. The initial compensatory response to hypoxia is an increase in fetal blood pressure and blood flow to the brain. If hypoxia does not improve, the blood pressure drops which results in a decreased blood flow to the brain known as ischemia. Unlike adults, fetal blood pressure changes cause more dramatic fluctuations in the blood flow to the brain. The fetal brain cells are deprived of oxygen and energy, the brain temperature drops which increases neurotransmitters such as gamma-aminobutyric acid transaminase (GABA). This decrease in temperature is a protective response to minimize asphyxia. However, a cascade of events eventually determines whether the brain survives or if damages can be reduced. The many biochemical reactions result in the buildup of toxins that damage brain cells leading to their death. As toxins and free radicals build up, calcium levels increase inside the cell, which causes more damage. The baby’s developing neurons (nerves in the brain) are uniquely susceptible to lack of oxygen, blood flow, and other insults [1-12].

Sarnat's criteria for the classification of HIE are based on six signs and their duration: alertness, activity level, muscle tone, reflexes, seizure activity, pupil size, and heart rate. With mild or grade I HIE, full recovery is common. With moderate or grade II HIE, reflexes may also be slow or absent, but if the baby improves within 1- 2 weeks, the final outcome is better. In severe or grade III cases, the severity and length of the seizures mean a worse prognosis.

Types of Cerebral Palsy

Acute, moderate, almost complete Hypoxic Ischemic Encephalopathy (HIE) causes damage to the basal ganglia and thalami deep in the brain. The results are athenoid or dystonic (dyskinetic) cerebral palsy (ADCP) with either intact or mild cognitive deficits. ADCP is a non-spastic type of CP and can exhibit both hypertonia (excess muscle tone) and hypotonia (limited muscle tone) due to the inability to control muscle tone [6].

The diagnosis of ADCP is most commonly made before 18 months of birth. The MRI is accurate in diagnosing over 50% of those with ADCP. These children require physical therapy and speech therapy. There are two types of ADCP, ataxic and dyskinetic. Dyskinetic forms can present with rapid and repetitive uncontrolled muscle movements such as grimacing and drooling.

There are eight clinical signs of cerebral palsy: abnormal muscle tone, persistent fetal reflexes (the ones that should disappear after birth), uncoordinated movements, asymmetric posture, ability to balance, fine motor skills such as hand/finger coordination, gross motor skills like walking, and vocal or oral dysfunction which impairs speech or swallowing.

According to one research article, among people with cerebral palsy, 3 in 4 are in pain, 1 in 2 are intellectually impaired, 1 in 3 cannot walk, 1 in 3 have a hip displacement, 1 in 4 cannot talk, 1 in 4 have seizures, 1 in 4 have a behavior disorder, 1 in 4 have bladder control problems, 1 in 5 have a sleep disorder, 1 in 5 drool or dribble, 1 in 10 are blind, 1 in 15 are tube fed, and 1 in 25 are deaf [15].

Cerebral Palsy: How Could Stem Cells Help

MSCs are ‘generic’ adult cells that have the capacity to differentiate into many different but specific cell types and have been identified in the bone marrow (BM), adipose, umbilical cord blood, placenta, and dental pulp. Much of the stem cell research for cerebral palsy relates to the use of this specific type of cell.

Mesenchymal stem cells (MSCs) are a promising therapeutic approach primarily due to their anti-fibrotic (anti-scarring), angiogenic (vessel growth), and immune-stimulating or modulating capacities. They act on the different processes that are dysregulated in various diseases. Recently, the therapeutic effectiveness of MSCs has been demonstrated in different preclinical animal trials and currently in phase I human trials. Both foreign (allogenic) and autologous (self) derived stem cells from bone marrow, or fat tissue are being evaluated [14].

Can Stem Cells have a therapeutic effect for cerebral palsy?

ST Cerebral Palsy research shows that Stem cell transplantation is one good option to treat CP patients. The potential mechanisms of stem cell transplantation in correcting or improving neurologic function are the following [13]: 

  1. Reducing the inflammation that may lead to secondary brain damage 
  2. Providing differentiating cells that turn into astrocyte, microglia, oligodendrocyte, neuronal and glial cells, which help the protective coating or myelin sheath, nerves regeneration, transmission of nerve impulses
  3. Producing the growth factors, such as glia derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT-3), neurotrophin 4/5 (NT 4/5), that support brain/nerve protection
  4. Making new vessels growth that increases the delivery of oxygen and nutrients to injured and hypoxic tissue; and
  5. Reducing cell apoptosis (death).

This meta-analysis of five trials demonstrated a positive short-term treatment effect for stem cell intervention on gross motor outcomes. It was suggested that better and long term positive outcomes might be expected if the stem cells were given closer to the time of injury. Many of the participants in this meta-analysis were 5 or older. 

The result of these trials provides support for the use of stem cells for cerebral palsy and is a key reason why many believe that the use of stem cells in the treatment of this and other debilitating afflictions is extremely exciting and the way of the future. 

References

  1. Paediatr Child Health Vol 11 NO 5 may/June 2006 278-282

  2. Hou, M; Zhao, J; Yu, R (2006). "Recent advances in dyskinetic cerebral palsy" (PDF). World J Pediatr. 2 (1): 23–28.

  3. O'Shea, MT (2008). "Diagnosis, treatment, and prevention of cerebral palsy in near-term/ term infants". Clin Obstet Gynecol. 51 (4): 816–828. PMC 3051278 . PMID 18981805. doi:10.1097/GRF.0b013e3181870ba7.

  4. "Athetoid Dyskinetic". Swope,Rodante P.A. Retrieved 31 October 2012.

  5. Krägeloh-Mann, I; Horber, V (2007). "The role of magnetic resonance imaging in elucidating the pathogenesis of cerebral palsy: a systematic review". Developmental Medicine & Child Neurology. 49 (2): 144–151. ISSN 0012-1622. PMID 17254004. doi:10.1111/j.1469-8749.2007.00144.x.

  6. Jones, MW; Morgan, E; Shelton, JE (2007). "Cerebral palsy: introduction and diagnosis (part I)". Journal of Pediatric Health Care. 21 (3): 146–152. PMID 17478303. doi:10.1016/j.pedhc.2006.06.007.

  7. Becher, JG (2002). "Pediatric rehabilitation in children with cerebral palsy: general management, classification of motor disorders". American Academy of Orthotists and Prosthetists. 14 (4): 143–149. Retrieved 29 January 2017.

  8. Black, Peter (1982). "Visual Disorders Associated with Cerebral Palsy". British Journal of Ophthalomolgy. 66: 46–52. PMC 1039711 . PMID 7055543. doi:10.1136/bjo.66.1.46.

  9. Facts about cerebral palsy. Centers for Disease Control and Prevention. (2012).

  10. "Cerebral Palsy Treatments". Education That Works. Retrieved 31 October 2012.

  11. Lundy, C; Lumsden, D; Fairhurst, C (2009). "Treating complex movement disorders in children with cerebral palsy". The Ulster Medical Journal. 78 (3): 157–163. PMC 2773587 . PMID 19907680.

  12. Aravamuthan, Bhooma R.; Waugh, Jeff L. (January 2016). "Localization of Basal Ganglia and Thalamic Damage in Dyskinetic Cerebral Palsy". Pediatric Neurology. 54: 11–21. PMID 26706479. doi:10.1016/j.pediatrneurol.2015.10.005.

  13. Novak, I., Walker, K., Hunt, R. W., Wallace, E. M., Fahey, M., & Badawi, N. (2016). Concise Review: Stem Cell Interventions for People With Cerebral Palsy: Systematic Review With Meta-Analysis. Stem cells translational medicine, 5(8), 1014–1025. doi:10.5966/sctm.2015-0372

  14. 10. da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. (2006) 119:2204–

    13. doi: 10.1242/jcs.02932



  15. Novak I, Hines M, Goldsmith S, et al. Clinical prognostic messages from a systematic review on cerebral palsy. Pediatrics. 2012;130:e1285–e1312.




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