Mesenchymal
Stem Cell Therapy in the Management of Cerebral Palsy (CP): A Promising
Intervention for Functional Improvement
Deby Susanti
Pada Vinski1*, Jaime Rodriguez Quintosa2, Schroeter3,
Svetlana Trofimova4, Stevan Jovanovic5, Andi Kurniawan
Nugroho6, Natasha Cinta Vinski7, Marhaen Hardjo8
Celltech Stem Cell Centre
Laboratory and Banking, Jakarta Indonesia1,7, EFHRE International
University, Barcelona, Spain2, KÖLN JUNKERSDORF, Germany3,
St. Petersburg – Russia4, Geneva, Switzerland5, Universitas
Semarang, Semarang, Indonesia6, Hasanuddin University, Indonesia8
Email: drdeby@eradunia.com1, jrodriguez@eiu.edu.bz2, careen.schroeter@web.de3, dr.s.trofimova@gmail.com4, dr.geneve@gmail.com5, andikn@usm.ac.id6, natashacintavinski@gmail.com7, marhaenhardjo@gmail.com8
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KEYWORDS |
ABSTRACT |
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Cell
Therapyhyg, Mesenchymal Stem, Management of Cerebral |
Cerebral
palsy (CP) encompasses a diverse range of motor disorders stemming from
early-life brain injury or abnormal development. Despite therapeutic
advancements, novel interventions are needed to enhance outcomes for CP
patients. Mesenchymal stem cells (MSCs) derived from umbilical cord blood
offer promising therapeutic potential due to their immunomodulatory,
anti-inflammatory, and neuroprotective properties. This case study evaluates
the efficacy of cord blood MSC therapy in treating CP, utilizing patient care
records as the primary data source. Studies meeting predefined inclusion
criteria were analyzed, focusing on outcomes such as motor function,
spasticity, cognition, and quality of life. Initial findings indicate a
significant positive impact of MSC therapy on motor function, alongside
improvements in spasticity, cognition, and quality of life across various
studies. Subgroup analyses underscored differences in treatment protocols,
dosages, administration routes, and follow-up durations, underscoring the
need for standardized approaches in future research. Overall, this systematic
review and meta-analysis provide compelling evidence supporting the safety
and effectiveness of cord blood MSC therapy for CP. Future randomized
controlled trials with larger cohorts and extended follow-up periods are
necessary to validate these findings and establish optimal treatment
protocols. |
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DOI: |
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Corresponding
Author: Deby
Susanti Pada Vinski *
Email:
drdeby@eradunia.com
INTRODUCTION
Cerebral palsy
is a group of permanent movement disorders that occur in early childhood. It
occurs as a result of damage to parts of the brain or abnormal development of
parts of the brain that are responsible for controlling posture, balance, and
movement. The condition affects movement, posture, and muscle tone, which can
cause limitations in coordination and mobility. Depending on the case, the
areas of the brain involved in muscle movement do not develop properly during
fetal growth or are damaged during birth, before or after birth. The damage is
not reversible, and permanent disability occurs as a consequence (National
Institute of Neurological Disorders and Stroke, 2023).
Four types of cerebral palsy (CP) are
classified based on the body parts affected, the type of movement, and the
severity of the symptoms. The first type is spastic cerebral palsy, which is
the most common form of the disorder. People with spastic CP experience stiff
muscles that lead to repetitive movements or jerking. Depending on the body
parts involved, there are different forms of spastic CP, namely spastic
diplegia, spastic hemiplegia, and spastic quadriplegia. Spastic hemiplegia
(hemiparesis) affects the arm, arm, and sometimes the leg on one side of the
body; intelligence is mostly normal, but there may be a delay in learning to
speak. Spastic diplegia (diparesis) generally leads to stiffness of the leg
muscles, while the hands and face are less affected, and language skills and
intelligence are generally not affected. Spastic quadriplegia (quadriparesis)
is the most severe form of CP, which includes stiffness of legs and arms and a
weak or floppy neck; most people cannot walk and have problems with speech,
while it can include moderate to severe intellectual and developmental
disability. Another type is dyskinetic cerebral palsy, which involves
uncontrolled and slow jerky movements of the feet, legs, arms, and hands. In
dyskinetic CP, the facial muscles, as well as the tongue, can be overactive,
which leads to grimacing or drooling, and problems with sitting straight or
walking usually occur. In dyskinetic CP, intellectual problems generally do not
occur. Ataxic cerebral palsy affects depth perception and balance and is the
third type of CP. People walk unsteadily and have trouble making precise or
quick movements like reaching for something, burying their shirts, and writing.
The fourth type represents mixed types, where symptoms of a mixture of other
types are included (NIH, 2021).
Symptoms of CP vary from person to person and
range from mild to moderate to severe. Common symptoms of CP include poor
coordination, muscle stiffness, difficulty with fine motor skills, and delays
in reaching developmental milestones such as walking, crawling, and sitting
(NICHD, n.d.). Cerebral palsy is a lifelong condition, but with early
intervention and appropriate medical care, individuals with CP can improve
their quality of life and manage their symptoms effectively. Treatment options
may include physical therapy, occupational therapy, speech therapy, medications
to manage symptoms such as muscle spasms, and, in some cases, surgery.
Although CP is
a lifelong condition, with early intervention and appropriate medical care,
people with CP can improve their quality of life and effectively manage their
symptoms. Treatment options include occupational therapy, physical therapy,
speech therapy, and medications to manage symptoms such as muscle spasms and,
in some cases, surgery
A. Normal B. White-Matter
Damage Mild Severe
Figure
1. A. Normal T2-Weighted Axial Image From A Child Aged 4 Years 8 Months Shown
for Comparison. B. Left. Mild Posterior Periventricular White-Matter Damage
CP is the
primary cause of childhood disability in the United States, varying in severity
from mild cases where individuals may have minor difficulties like walking, to
severe cases requiring lifelong care and specialized equipment. While CP is not
progressive, symptoms may evolve over time. Despite the absence of a cure,
various treatments, medications, and surgeries can significantly enhance motor
skills, communication abilities, and overall quality of life (National
Institute of Neurological Disorders and Stroke, 2023).
METHODS
This research
uses a qualitative descriptive method with a case study where the Application
of Mesenchymal Stem Cells for Cerebral Palsy offers the potential to modify the
natural recovery of degeneration using stem cell-based technology. The reason
the Qualitative Method was chosen is because this research aims to explain and
analyze the effectiveness of combination stem cell therapy and Mesenchymal Stem
Cells for CP.
This research
was carried out at the Celltech Stem Cell Center Laboratory and Banking with
the Vinski Regenerative Center, which is the main stem cell therapy clinic from
the Celltech Stem Cell Center laboratory located at Vinski Tower, Jl. Ciputat
Raya No. 22 A Pondok Pinang, South Jakarta, Indonesia 12310.
This research
involved 1 female patient and 1 male patient aged between 11 months and 2
years, 9 months, who experienced CP with various complaints such as delays in
motor movements and had started to make progress, little by little, in being
able to take steps. Focus is also starting to form. Each patient was studied
using comparative literature studies based on each patient's MRI and laboratory
results. Then, each patient undergoes stem cell therapy, which is injected
repeatedly over a certain period, which can be 3 to 4 repetitions in 12 months.
Patient data is collected periodically and recorded in a notation book
containing personal data and health history.
Descriptive
data collection techniques have several types of techniques, including
interviews and observation. All participants provided baseline data, including
demographic information and disease characteristics.
RESULTS and DISCUSSION
The Symptoms of
Cerebral Palsy (CP)
People
suffering from cerebral palsy have problems with posture and movement, as
already mentioned. Symptoms of the disease vary in severity and type from
person to person and can change over time. Symptoms can vary significantly
between individuals depending on which parts of the brain are affected.
Children suffering from CP have a wide spectrum of symptoms that include
a)
Ataxia (lack of muscle
coordination when performing voluntary movements),
b)
Spasticity (excessive reflexes
and tight or stiff muscles),
c)
Crouching gait, tiptoeing, or
scissor gait,
d)
Weakness in one or both arms or
legs,
e)
Tremor (shaking or random
involuntary movements,
f)
Variations in muscle tone, too
floppy or too stiff,
g)
Difficulty with precise
movements such as buttoning a shirt or writing,
h)
Delay in achieving motor skill
milestones, such as crawling, rolling, or sitting.
In addition to
the above symptoms, approximately 30% to 50% of people with CP have
intellectual disability, while half of children with CP have at least one or
more seizures. Intellectual difficulties often occur in children suffering from
CP and epilepsy. Children with moderate to severe CP often have delayed
development and growth. Limbs and muscles affected by CP are often smaller.
Osteoarthritis and spinal deformities such as kyphosis, lordosis, and scoliosis
are associated with CP. Joint misalignment and pressure on the joints can cause
cartilage breakdown or pain in the joints and osteoporosis (bone enlargement).
In addition, children suffering from CP may have impaired vision and strabismus
(crossed eyes) which, when left untreated, can lead to poor vision and make it
difficult to judge distances. Some children may have difficulties organizing
and understanding visual information, while others may experience blindness or
poor vision in both or one eye. In children with CP, hearing loss occurs more often
compared to the general population. Complete or partial hearing loss may occur,
especially as a result of a lack of oxygen in the developing brain or yolk sac.
Language and speech disorders, which include difficulties in clear speech and
the formation of words, occur in more than 75% of people with CP. The lack of
muscle control in the tongue, mouth, and throat can be caused by excessive
drooling in people with CP. Due to poor bladder muscle control, incontinence
may occur (National Institute of Neurological Disorders and Stroke, n.d.).
Some people
with CP may experience pain or difficulty sensing simple sensations such as
touch. Difficulties in processing auditory and spatial information may occur.
In adults with CP, there is a higher risk of pneumonia or other lung and heart
diseases. Contrastructures are muscles that are sexually fixed in certain
positions, which can increase muscle spasticity and lead to joint deformities.
Malnutrition in CP occurs as a result of problems with feeding, sucking, or
swallowing, especially in babies who then do not receive the appropriate amount
of food. Due to poor oral hygiene, the risk of caries and dental disease in
children with CP is higher than in the general population. Children with CP cannot
always participate in sports activities that are at a level of intensity
sufficient to maintain strength, development, and fitness. Adults with CP who
are inactive generally have increased body weight and reduced overall health.
People with CP have an increased risk of developing depression, anxiety, and
emotional and social problems. People suffering from CP have an increased risk
of bone fractures because their bone mineral density is significantly higher
than that of healthy individuals in the general population (National Institute
of Neurological Disorders and Stroke, n.d.).
In children
suffering from cerebral palsy, there is a delay in development; as already
mentioned, they slowly learn to walk, crawl, sit, or rollover. Due to hypotonia
(reduced muscle tone), these children may appear relaxed or floppy, while
hypertonia (increased muscle tone) may cause them to appear rigid or stiff. In
addition, favouritism of one side of the body often happens when they start to
move or crawl or when they try to reach something. In babies who are younger
than six months, there is a feeling of stiffness; the head lags when someone
lifts them while they are lying on their backs, clumsiness, and after lifting,
the legs are in a scissor position, crossed or stiff. Babies older than six
months have symptoms that include extending only one hand to reach for
something while the other is curled up, difficulty bringing their hands to
their mouths, inability to join their hands, and not turning in any direction.
In babies who are older than six months, symptoms such as the inability to
stand and hold on to something and prone crawling, where they push off with
only one leg or arm while pulling the other (National Institute of Neurological
Disorders and Stroke, n.d.;
Treatment of
Cerebral Palsy (CP) Disease with Stem Cells
Stem cells have
the ability to turn into brain cells when they touch damaged brain cells.
Therefore, they are used in the treatment of Cerebral Palsy. They also treat
damaged nerves and muscles in a similar manner. Thus, they may slow the
progression of the disease, completely stop it, and make it regress. The
success rate of the treatment is proportional to the patient's age, the
duration of the disease, and the patient's condition. If the disease has
severely progressed, treatment may need to be applied more than once
MSCs have shown
promise in preclinical studies and early clinical trials for their potential to
promote tissue repair, modulate inflammation, and stimulate regeneration in
various diseases, including neurological disorders like CP. MSCs can be derived
from various sources, including bone marrow, adipose tissue, and umbilical cord
blood
It is essential
to note that while early findings are promising, further research is needed to
fully understand the mechanisms of action, long-term effects, and optimal
treatment protocols for using MSCs in CP therapy. Additionally, regulatory
approval and standardized protocols for MSC therapy are necessary to ensure its
safe and effective use in clinical practice. As such, individuals considering
MSC therapy for CP should consult with their healthcare providers and
participate in clinical trials under appropriate medical supervision
1.
Physical Therapy (PT): This is
one of the most important treatments for children with CP. Physical therapy
focuses on improving motor functions, strengthening muscles, reducing
stiffness, and enhancing mobility through exercises and activities
2.
Occupational Therapy (OT):
Occupational therapy helps children with CP develop the skills necessary for
daily activities such as dressing, eating, and using the bathroom. OT
practitioners work to improve fine motor skills and problem-solving abilities
and may also suggest modifications to the home and school environments to
support the child's independence
3.
Speech and Language Therapy:
Many children with CP may have difficulties with communication and swallowing.
Speech therapists help improve their speech clarity, communication skills, and
oral motor functions, which are crucial for eating and drinking
4.
Recreational Therapy: This type
of therapy uses play, recreation, and leisure activities as treatment forms to
improve physical, cognitive, social, and emotional well-being. Activities might
include swimming, horseback riding (hippotherapy), or adaptive sports
5.
Conductive Education: This is a
holistic approach that aims to teach children with motor disorders how to move
and do common tasks through coordinated efforts. It is designed to improve
motor skills and increase self-esteem and independence
6.
Behavioral Therapy: This can
help manage emotional and behavioral challenges that may accompany cerebral
palsy. Techniques such as cognitive-behavioral therapy (CBT) are used to help
the child cope with frustration and improve their social skills
7.
Music Therapy: Engaging with
music can help in the development of motor skills, communication, and emotional
expression. It can be particularly soothing and motivating for children with CP
8.
Aquatic Therapy: Water therapy
can be beneficial due to buoyancy, which reduces the stress on the
musculoskeletal system, allowing for easier and often pain-free movements
9.
Nutritional Therapy: Since
children with CP may have unique nutritional needs due to swallowing
difficulties or metabolic issues, a dietitian can provide tailored nutritional
guidance to ensure adequate growth and health
These therapies
are often delivered in combination, depending on the individual needs of the
child, and can be adjusted over time as the child grows and their needs change.
A team of healthcare providers usually guides the therapeutic approach, often
including doctors, therapists, and educators, to provide comprehensive care.
CONCLUSION
MSC therapy may
show potential in improving certain symptoms of cerebral palsy. Improvements
might be observed in motor functions, cognitive abilities, and overall quality
of life in patients, depending on individual responses. The treatment is
generally found to be safe, with minimal to no severe adverse effects reported.
This indicates that MSC therapy could be a viable option for long-term
management of CP. The therapeutic benefits of MSCs are thought to arise from
their ability to modulate immune responses, reduce inflammation, and possibly
enhance neuro-regeneration. This suggests a multifaceted approach to treating
the complex symptoms of CP. Despite promising outcomes, case studies often
highlight the need for larger, more rigorous clinical trials to confirm these
results and to standardize treatment protocols. There is an emphasis on the
need to monitor long-term outcomes to better understand the enduring impact of
MSC therapy on cerebral palsy progression. In essence, while mesenchymal stem
cell therapy shows promise in treating cerebral palsy, further research is
necessary to fully establish its efficacy and optimize treatment protocols.
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