MichelleC

~ STEM CELL TREATMENT IN CEREBRAL PALSY ~

Introduction


I have always heard of the controversy over stem cell research in the news, but I never fully understood what it meant. Only recently, I learned a general overview of stem cells and the controversy of stem cell research. However, I still felt ignorant about this topic. When this project came around, I knew exactly what I wanted to do.

At first, I wanted to do this project on stem cell treatment for neurological disorders, but as I was researching, I found that one of the disorders that is being treated with stem cells is cerebral palsy. I have a very good friend who has CP, and I thought that narrowing my topic would not only help me focus on one aspect of neurological disorders but also relate to it on a more personal level.

From what I learned in science class, stem cells are cells that can be altered to become any type of cell (i.e. bone cell, skin cell, etc.) I also learned why stem cell research is so controversial in America. Earlier, it was thought that the best types of stem cells are from the embryo since these cells have the most potential to turn into any type of cell with a specialized job. However, some believe
that creating embryos with in vitro (in a controlled environment, particularly a lab) fertilization for stem cells constitutes as murder. The United States is built on ethics and a set of morals. Since we are a diverse country, there is one side that believes that stem cell research is ethical and another side believing that it is unethical. Unfortunately, we live in a country that is locked in the beliefs that stem cell research is immoral. Therefore, scientists who want to be part of this dynamic future in genetics are going to countries where stem cell research is not regulated (such as places in Asia - mostly Singapore and China).


1.jpg
Stem Cell Mechanism
[1]
The following are fun interactive websites about stem cells. I would highly recommend visiting these sites because they have great animations and comprehensible explanations.
What is a Stem Cell?
What are Some Different Types of Stem Cells?


As this page contains information about stem cell treatment for cerebral palsy, I will first briefly introduce this topic. Most common neurological disorders are caused by the loss or damage of neurons or neuroglia (supporting cells of the nervous system).[2] Neurons do not replicate or divide through mitosis nor are neurons in the brain able to repair themselves after damage.[3]
B
ecause of this, scientists are beginning to try to create nerve cells from stem cells in order to combat these neurological disorders.
Cerebral palsy (CP) has a wide variety of symptoms depending on the severity of the case, but all involve the brain and nervous system. The causes of cerebral palsy are injuries or abnormalities of the brain. The injuries primarily occur in the mother's womb or during the first two years of the infant's life. Presently, there is no cure for CP (although there are treatments and therapy for relief of some symptoms).[4]
The rest of this page will explore this topic in depth. Enjoy!




Background

Stem Cells

To summarize the information shown on the interactive websites (listed in the Introduction), stem cells are cells within the body that do not have a set function. A stem cell slowly divides until it is given a signal to differentiate or change into a determined cell type. When the cell is differentiating, it begins to activate certain genes in its genome to make proteins. After differentiation, the cell will stop dividing and multiplying its numbers.[5]

However, not all stem cells are capable of becoming any type of cell. Early embryonic stem cells are totipotent, which means that they can become any type of cell. When the sperm and egg fuse into the zygote (the fertilized egg), the zygote begins to divide, and these beginning cells are early embryonic stem cells.


3.jpg
Totipotent Cells
[6]

Surrounded by the outer lining of the blastocyst, a hollow round structure formed seven days after fertilization, are blastocyst embryonic stem cells which are pluripotent. Pluripotent means that the stem cells can become almost all types of cells within the body.


2.jpg
[7]
By the eighth week, the embryo has formed into the fetus which starts to resemble a human-like form. Like blastocyst embryonic stem cells, fetal stem cells are pluripotent. The next type of stem cells are umbilical cord stem cells which are multipotent. Multipotent stem cells can become only a limited number of cell types.


Fetus
Fetus
[8] Adult stem cells come from stem cells in a human after being born (includes all ages). These stem cells are multipotent.[9]

Adult Stem Cells
Adult Stem Cells
[10]

Cerebral Palsy


Technically, cerebral palsy is not a specific neurological disorder, but instead, it refers to any number of disorders that affect a child's body movement and coordination during infancy to early childhood. The symptoms are caused not by damaged muscles or nerves, but abnormalities in parts of the brain that control movement. Patients of cerebral palsy have the disorder their whole lifetime. The symptoms do not worsen over time and the disorder is not contagious.[11]

Causes

The causes of cerebral palsy is brain damage. The brain damage occurs during birth or shortly after, and either happens because of developmental brain malformation (which is the failure of the brain developing properly) or neurological damage to the brain. Some causes of cerebral palsy are infection, bleeding in the brain (hemorrhage), lack of oxygen, or diseases.[12] In many cases, cerebral palsy can be prevented from contraception, to childbirth, and into the first few years of the child's life.[13]

Types of Cerebral Palsy
Types of Cerebral Palsy
[14]

Symptoms

There are a wide variety of symptoms and cases ranging from mild to severe:
  • Abnormal movement and posture
    • Walking gait (asymmetrical - foot or leg dragging on one or both sides)
    • Tremors
    • Difficulty in muscle coordination and motor skills
    • Weak muscles
    • Struggles with swallowing, sucking, or speaking
    • Drooling
    • Uncontrollable reflexes and movement of arms, body, and legs[15]
cerebral_palsy2.gif
Cerebral Palsy Movement
[16]

Treatments

CP is not curable, but some symptoms can be relieved so that the child will improve his or her capabilities.
  • Physical therapy
  • Occupational therapy
  • Speech therapy
  • Medicine and drugs for seizures, muscle spasms, and pain
  • Surgery for abnormal body structures or to release tight muscles
  • Aids - braces, wheelchair, rolling walkers, and communication aids
Child with CP
Child with CP

[17]


History

Since the history for stem cell treatment for cerebral palsy is recent, I am going break up my topic into three parts. First, I will give a time line on cerebral palsy, and then a time line on stem cell treatment. Finally, I will finish with the recent news on treating cerebral palsy with stem cell therapy.

Cerebral Palsy

1861: The British orthopedic surgeon William Little was the first to record medical descriptions of cerebral palsy. He noted that patients had difficulty with motor skills, and they had tight and spastic limbs. He observed that patients were born premature or had a difficult delivery, so he hypothesized that the disease was caused by lack of oxygen during childbirth. The disorder was named Littles Disease.

1887: Sir William Osler coined the term "cerebral palsy" and wrote on central nervous system injuries. Also, two writings, "The Natural History of Cerebral Palsy" by Crouthers and Payne and "Orthopedic Management of Cerebral Palsy" by Eugene Bleck, contained information of diagnosis and management of cerebral palsy patients.

1897: Dr. Sigmund Freud published papers on his belief that cerebral palsy began earlier in the birth (perhaps during the development of the fetus). He noted that symptoms varied greater than just struggles with motor skills. Patients had vision problems, mental deficiencies, and seizures.

1980s: A government funded study collecting information of 35,000 cerebral palsy births gives evidence that few cases involved difficulty during childbirth.

1990s: There was progress in early diagnosis (brain imaging) so as to prevent permanent contracture of the limbs. Therapies as well as identification of risk factors improve.

Recent: Three new therapies are successful in treating cerebral palsy: the surgery, selective dorsal rhizotomy, stops spasms in specific muscle groups, primarily in the legs; limbs have an increased range of motion when injected with Botox; the Baclofen pump relieves muscle tension by injecting a drug to the spinal chord nerves.[18] Also, stem cell therapy is attracting patients to parts of the Eastern hemisphere.




Stem Cells

Stem cell research began in the mid 1800s when the Western countries began manufacturing finer microscopes.[19] With the microscopes inspecting the smaller levels of nature, scientists realized that cells where the building blocks of life and were capable of reproducing and differentiating into cells with a specific job. It was not until the early 1900s that researchers found the first stem cells that were capable of producing different types of blood cells.[20]

1958: Leroy Stevens publishes about the pluripotent nature of a strain of mice cells.
1970: Leroy Stevens notes that cells that are able to differentiate when injected into adult mice tissues. He names the cells ES cells.
1975: Beatrice Mintz and Karl Illmensee find that ES cells can create organisms.
1981: Martin Evans and Gail Martin culture pluripotent mice ES cells.
1985-1992: Brigid Hogan and Peter Donovan's group find that culturing ES cells in specific medias can cause the cells to differentiate.
1993: President Bill Clinton creates the NIH Human Embryo Research Panel to preside over ethical sides of fetal and embryonic research.
1998: Two research groups create stem cell lines from embryonic tissue.
1999: Researchers differentiate human mesenchymal stem cells from bone marrow into cartilage, fat, and bone cells.
1998-2002: Dr. Michel Levesque removes stem cells from a patient suffering from Parkinson's disease. He allows them to grow and later returns the neuronal stem cells and neurons into the patient. The patient's motor skills improve and the brain stops degenerating.
2000: Martin Pera and colleagues create human embryonic stem cell lines and show that ES cells are able to differentiate into neuronal progenitor (more specific than stem cells) cells.
2001: Researchers in Virginia get stem cell lines from human embryos for research.
2002: Ole Isacson's group find that untreated mouse ES cells can differentiate into dopamine-producing neurons. These neurons can be used to treat animals showing Parkinson disease-like symptoms; it reduces symptoms by 40 percent. However, some test-rats died from tumors.
2005: Alison Murdoch and Miodrag Stojkovic create human blastocysts by cloning.
2006: President Bush approves the Fetal Farming Prohibition Act and vetoes the Stem Cell Research Enhancement Act.[21]
2009: President Obama issues Removing Barriers to Responsible Scientific Research Involving Human Stem Cells which changes how the National Institute of Health (NIH) can support and work on human stem cell research.[22]

For more information and a more detailed explanation on the history of stem cells up to 2006, please visit: Stem Cells Timeline
I also attached the link to the pdf file of President Obama's Removing Barriers to Responsible Scientific Research Involving Human Stem Cells


Stem Cell Therapy for Cerebral Palsy

Since stem cell therapy for cerebral palsy is relatively new, I found information regarding the treatment and outcome on two individuals.
Kaelyn Sosa's Treatment in China
and
19-year old Gabor Bocskai's Treatment in China

The first link is about Kaelyn Sosa who has had numerous stem cell injections from a hospital in China. With the addition of numerous therapies (physical, occupational, electric wave, and acupuncture), Kaelyn has had 6 umbilical cord blood stem cells and 1 bone marrow aspiration injections. These stem cells will become nerve and brain cells that can help improve functions and repair damaged tissue. Her parents have noticed an increase in strength, alertness, head movement, and controlled movement.[23]

Also in China, Gabor Bocskai was treated at Tiantan Puhua Neurosurgical Hospital where neural stem cells were injected into his cerebrospinal fluid at his spinal chord by a lumbar puncture. The fluid then carried the neural stem cells to his brain. After the stem cell therapy, Bocskai was had improved vision, clearer writing, increased concentration, and improved muscle tone. He was also able to walk with the aid of a walker.
[24]

Additionally, on a bigger scale and recently, Dr. James Carrol of the Medical Center of Georgia has conducted the first FDA approved stem cell therapy trial on cerebral palsy for children. Doses of umbilical cord stem cells were injected into forty children from age 2-12.[25] For more information read this article.



Explanation

Process

Patients can either have the stem cells injected into spinal chord or directly into the brain.
If the stem cells are injected into the spinal chord, it will go up to the brain by traveling with the cerebrospinal fluid.


Cerebrospinal Fluid
Cerebrospinal Fluid
[26] If the stem cells are injected directly into the brain (which is more accurate), it will be surgically implanted there.
Day 1
Bone marrow is collected from the hip bone with a thin-needle mini-puncture (anesthesia will be needed). This normally takes half an hour. The patient will be able to resume normal daily activities after this (however if general anesthesia is applied, the patient should rest for a while before returning to the hotel).

Day 2
Stem cells are processed from the bone marrow in a laboratory. They are checked for amount and quality. These types of cells are able to differentiate into a number of cells. Additionally, they can repair damaged tissue.

Day 3
Stem cells are injected to the patient.
Lumbar puncture (into the spinal chord): A needle will take out a small quantity of cerebrospinal fluid (fluid of the nervous system) between the vertebrae.

Lumbar Puncture
Lumbar Puncture
[27]
The sample of cerebrospinal fluid will be mixed with the stem cells and inserted back into the spinal fluid. After the procedure, the recovery time is up to the fifth day.

Surgical implantation (into the brain): Before the surgery, affected brain regions will be identified using computer tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). An example is shown below. Afterwords, the neurosurgeon will implant the stem cells through the patient's skull. Once the needle reaches the cerebrospinal fluid space, the stem cells will be released. This procedure requires general anesthesia. The recovery time at the hospital is up to ninth or tenth day.


Brain Images
Brain Images
[28]


At XCell-Center in Germany -
Cost for lumbar puncture implantation: 9,000 Euros for children (about $11,048) and 7,995 Euros for adults (about $9,814)
Cost for surgical implantation: 25,500 Euros ($31,303)
[29]

Results

*The following results are from the XCell-Center in Germany.
Out of 100 patients at the center, 70% reported improvement. The following graphs will show the results:


Results
Results

Upper Extremeties
Upper Extremeties


Lower Extremeties
Lower Extremeties

Other Improvements
Other Improvements

[30]

The following are videos found on YouTube of a patient who has had stem cell therapy.
Before













After



Connections

1. Gene Regulation and Operons
Because "for human ES [embryonic stem] cells almost nothing is known about the regulation of self-renewal and pluripotency", I will relate this as best I can to the "Gene regulation and Operons" section we learned.[31] Stem cells have many unique properties, one of them being their ability to become specialized cells. Through differentiation, the stem cell becomes more specialized as the stages progress, and there are signals within and outside of the cell that trigger this process. Unfortunately, scientists have not understood the differentiation process yet. What they do know is that the internal signals are controlled by the cell's genes which code for all of the cell's structures and jobs. The external signals are caused by chemicals secreted by neighboring cells and contact between adjacent cells. Additionally, certain molecules and chemicals in the habitat of the cell could trigger an event. The combination of internal and external signals create daughter cells that have the same epigenetic (proteins that turn on and off genes) marks as their mothers.[32]

2. Mitosis
Although neurons, the cells of the nervous system, might be a small part of my project, the fact that neurons do not undergo a mitotic phase has determined the consequences of neurological diseases. Neurons are amitotic which means that they do not divide; once they are destroyed, they cannot be replaced.[33] Brain cells are neurons. Since cerebral palsy deals with brain damage or abnormalities, the damaged brain tissues cannot repair because the neurons are not capable of reproducing (and this is where stem cell therapy comes in since it introduces healthy nerve cells that are able to repair damage).




Social and Ethical Implications

Before 2007 when researchers depended on embryonic stem cells for research, the controversy was much more heated since some believed that taking embryos for scientific research was murder.
Cartoon
Cartoon
[34]


Stem Cell Research Pros
  • Could treat and possible cure a number of diseases (Parkinson's Disease, Alzheimer's Disease, heart diseases, birth defects, spinal chord injuries, damaged organs, cancer, creating cloned organs for transplants)
  • This could lead to beneficial changes in the society.

Stem Cell Research Cons

  • Religion - "Humans should not be playing with God"
  • Human life should not be changed drastically.
  • Some believe that stem cell research will lead to knowledge of human cloning.[35]

There is also controversy over current stem cell therapies since most Eastern therapies have not been approved by the U.S. or the UK. Some are skeptical whether these therapies will improve a patient's symptoms. There are also risk factors including the growth of tumors from not being able to control the growth of the stem cells.

Additional Information:
Time's Article on the Stem Cell Research Controversy




Potential Futures


What the Experts have to Say
Dr. James E. Carroll, chief of the Medical College of Georgia Section of Pediatric Neurology, received a grant from the American Heart Association and National Institute of Health and is experimenting the most effective way to transplant stem cells using an animal model of cerebral palsy. "Although he thinks there is potential for stem cell therapy to one day help restore function lost to the group of disorders known as cerebral palsy, many unanswered questions remain. One concern is whether these proliferating young cells might cause tumors. Also, cerebral palsy is not a single problem, but a complex disease in which virtually all brain cell types could need repair."[36]

According to the University of Utah's Genetic Science Learning Center, researches are working on creating more effective and harmless stem cell therapies. [37]

In the NIH Stem Cell website, studies on human embryonic stem cells could potentially be used to explain the events of human development and how cells can differentiate and form tissues and organs. Since scientists understand that a cell is capable of turning genes off and on, they could, through research, find the cause of abnormal cell division (cancer) and differentiation. This would be helpful for cancer victims and those born with defects. These studies could also yield crucial information about diseases which will then lead to appropriate therapies. Human stem cells could also be used for testing new drugs, and most importantly, as treatment for disorders and diseases.[38]

What I think
I believe it is crucial for stem cell research to continue. There are brilliant children who are disabled by disorders such as cerebral palsy, and if stem cell therapy will (in the future) cure the disease, our world will be more diversified and our society will benefit from their presence. However, I do not think there should be stem cell therapies until all risks (such as cells becoming cancerous) are cleared and there is enough evidence that stem cell therapies will benefit the patient.

  1. ^ http://www.boncherry.com/blog/wp-content/uploads/2010/02/stem-cell-cultivation.gif
  2. ^ http://www.nature.com/nature/journal/v441/n7097/full/nature04960.html
  3. ^ http://www.wisegeek.com/what-is-a-neuron.htm
  4. ^ https://health.google.com/health/ref/Cerebral+palsy
  5. ^ http://learn.genetics.utah.edu/content/tech/stemcells/scintro/
  6. ^ http://www.wnd.com/images/stemcell1.gif
  7. ^ http://biomed.brown.edu/Courses/BI108/BI108_2008_Groups/group10/img/stem/0.jpg
  8. ^ http://www.thesho.com/EaglezeYe/FETUS.JPG
  9. ^ http://learn.genetics.utah.edu/content/tech/stemcells/sctypes/
  10. ^ http://www.herdaily.com/blogimg/health/Adult%20Stem%20Cells.jpg
  11. ^ http://www.ninds.nih.gov/disorders/cerebral_palsy/cerebral_palsy.htm
  12. ^ http://www.about-cerebral-palsy.org/diagnosis/causes.html
  13. ^ http://www.cerebralpalsysource.com/About_CP/brain_injury/index.html
  14. ^ http://www.passenlaw.com/blog/wp-content/uploads/2010/03/cerebral-palsy-types.gif
  15. ^ http://www.mayoclinic.com/health/cerebral-palsy/ds00302/dsection=symptoms
  16. ^ http://prehealthfig2008.wikispaces.com/file/view/cerebral_palsy2.gif/49049107/cerebral_palsy2.gif
  17. ^ http://www.passenlaw.com/blog/wp-content/uploads/2010/03/Cerebral-Palsy-Birth-Injury.jpg
  18. ^ http://www.livingwithcerebralpalsy.com/cerebral-history.php
  19. ^ http://inventors.about.com/od/mstartinventions/a/microscope.htm
  20. ^ http://www.allaboutpopularissues.org/history-of-stem-cell-research-faq.htm
  21. ^ http://www.garlandscience.com/textbooks/cbl/stemcell/corematerials/timeline.html
  22. ^ http://edocket.access.gpo.gov/2009/pdf/E9-5441.pdf
  23. ^ http://www.stemcellschina.com/index.php/en/patient-experiences/cerebral-palsy/1331-kaelyn-cp
  24. ^ http://www.cerebralpalsy.org/cerebral-palsy-medical-news-and-breakthroughs/cerebral-palsy-and-stem-cell-treatment-dramatic-results-in-china/
  25. ^ http://www.health.am/ab/more/fda-approved-stem-cell-trial-in-pediatric-cerebral-palsy/
  26. ^ http://health.stateuniversity.com/article_images/gem_02_img0158.jpg
  27. ^ http://www.frca.co.uk/images/pain_lumbar_puncture.gif
  28. ^ http://www.xcell-center.com/media/48299/surgical-implantation.png
  29. ^ http://www.xcell-center.com/treatments/diseases-treated/cerebral-palsy.aspx
  30. ^ http://www.xcell-center.com/treatments/results/cerebral-palsy.aspx
  31. ^ http://www.pnas.org/content/100/23/13350.full
  32. ^ http://stemcells.nih.gov/info/basics/basics2.asp
  33. ^ http://www.daviddarling.info/encyclopedia/N/neuron.html
  34. ^ http://thumpandwhip.com/wp-content/uploads/2010/01/stem-cell-cartoon.jpg
  35. ^ http://www.experiment-resources.com/stem-cell-pros-and-cons.html
  36. ^ http://www.sciencedaily.com/releases/2004/08/040817075814.htm
  37. ^ http://learn.genetics.utah.edu/content/tech/stemcells/scfuture/
  38. ^ http://stemcells.nih.gov/info/basics/basics6.asp