Umbilical cord blood derived stem cell therapies for Stroke and traumatic brain injury


By James Braly, M.D.
Senior Medical Director
Weller Health Institute

A.B., a 77 year old businessman was paralyzed by a stroke in 2002. A year later he received an injection of umbilical cord derived stem cells. Within three weeks, A.B. had regained 80% of his strength and motor function in his previously weak and paralyzed arm and leg.

Similar anecdotal results are being reported around the world from the use of human stem cells for the treatment of stroke, traumatic brain injury, cerebral palsy, multiple sclerosis, ALS, and macular degeneration.

What are stem cells?

At the beginning of life is the "FIRST CELL" (zygote). This cell is "totipotent", i.e., capable of generating every other cell of the body. As this FIRST CELL divides into many cells, it forms different embryonic layers (the ectoderm, mesoderm and endoderm).

The outer ectoderm layer becomes specialized into brain and spinal cord nerve cells with their supporting cells (glia). The glia help nourish and protect the neurons by forming a layer of insulation around them, much like the black insulation around electrical wires in your house. Instead of being black, the glia are white and form the "white matter" of the brain and the blood-brain-barrier.

This white matter is partially destroyed in multiple sclerosis, stroke, traumatic brain injury, cerebral palsy and congenital brain disorders but appears to be repairable with stem cells.

Stem cells that come from the mesoderm make red blood cells, white blood cells and platelets, as well as bone, muscle, fat, cartilage and skin.

Stem cells of the endoderm develop into cells for the digestive system and lungs. Of greatest interest and practicality is that the different stem cells are "multipotent" and can replace damaged tissues anywhere in the body.

What are the different sources of stem cells?

Three basic sources of stem cells include:

  1. embryonic stem cells derived from aborted fetuses or fertilized eggs,
  2. umbilical cord blood derived stem cells, and
  3. adult stem cells which are isolated from an adult’s tissues (such as the bone marrow, fat, or blood) and then grown in tissue culture.

Embryonic stem cells currently present a number of difficulties, including abortion and laboratory fertilization controversies. Embryonic lines that are approved for research may be losing their potency over time. They may contain mouse feeder cells and no longer be "pure" human cells. In addition, serious Graft Versus Host complications have been reported in patients treated with embryonic stem cells outside the U.S. This could result from embryos having genetic aberrations and diseases from uncontrolled parental sources. Quality control for purity and potency is a major concern with the use of embryonic stem cells.

Unfortunately, adult derived stem cells are also associated with Graft Versus Host Disease.

Umbilical cord derived stem cells are easily obtainable. They can be certified for purity and potency, and are much safer to use than embryonic or adult stem cells. At this time, umbilical cord derived stem cells may offer the best results with the least liability. 

Umbilical Cord Derived Stem Cells

CD34+ stem cells are now available that have been specially extracted from umbilical cord blood and which are similar in biological activity to stem cells taken from human embryos. CD34+ stem cells (named for having a specific human leukocyte differentiation antigen) are able to (1) divide symmetrically to re-create themselves and their multipotent capacity (self-renewal) and (2) through asymmetrical division, give rise to a variety of functional cells such as blood cells, immune cells, liver cells, neurons, etc. 

Safe and Effective Track Record Since 1986

Umbilical cord blood has been approved for use by the FDA since the late 1980’s. Umbilical cord blood transfusions (which included CD34+ stem cells) have been used since 1986 in the United States in over 1,000 patients, both children and adults. Many of these treatments were for cancer patients who showed significant improvement after treatment. Thus cord blood stem cells are the "active" portion of the cord blood used to repair the bone marrow and immune system in patients treated with chemo and radiation therapy. In addition, umbilical cord blood (with its stem cells) has a 17 year track record of being used to treat cases of malignancy without increasing the risk of developing subsequent malignancies. Cord blood produces significantly less Graft Versus Host disease and is easier to obtain than bone marrow stem cells. In addition, only cord blood that is AABB (American Association of Blood Banks) certified is used.

Graft Versus Host Disease

New methods of separating stem cells from all other blood components associated with Graft Versus Host disease have resulted in a product that consists of only stem cells. Since these umbilical cord stem cells are immature and have not developed ABO and HLA antigens on their surfaces, they do not induce graft versus host reactions that may occur with embryonic, bone marrow stem cells or to a lesser degree, cord blood. Since the umbilical cord stem cells do not contain mature blood or tissue cells, foreign protein reactions do not occur. This is important because immune suppressive chemotherapies and radiation used in the past with bone marrow and cord blood transplants are toxic to stem cells and new neurons. Both chemotherapy and radiation are associated with neurotoxicity and symptoms of memory loss, depression, and declining IQ scores.

Therefore if "pure" umbilical cord derived stem cells (separated from blood components) are safe enough to use without immune suppressive therapies, the stem cell therapy should be more effective. This is what is being reported from patients being treated in other countries. CD34+ stem cells extracted from cord blood are being reported as safe and effective without the use of immune suppression.

Augmentation

The effectiveness of stem cells can be improved by increasing their numbers. Each umbilical cord/placenta unit contains 80-220 ml of blood and an average unit of 100 ml of cord blood contains 300,000 stem cells. These stem cells can be stimulated by growth factors in the laboratory to replicate up to several million stem cells that still retain their potency and viability.

We know at this point that a million stem cells per treatment is more effective than 300,000 stem cells and the larger dosage further reduces Graft Versus Host complications.

A subset of CD34+ stem cells are progenitor cells that give rise to new neurons. For brain injured patients, therapies can be created where 80% of the treatment consists of primitive neural progenitor cells called CD133+ cells.

How Stem Cells Help the Healing Process

When stem cells are injected intravenously, intramuscularly or subcutaneously, they travel to those parts of the body that have suffered from some type of injury. At these sites of injury, the blood vessels have been damaged, narrowed and constricted. These constrictions prevent the oxygen carrying red blood cells from passing through to the tissues, which produces areas of reduced oxygen. Since stem cells are large, they become lodged in these narrowed and constricted small blood vessels. The low levels of oxygen in these damaged areas are just what the stem cells need to grow and develop. In addition, endothelial cells, the inner lining of the damaged blood vessels, express certain signals that attract the stem cells.

In the early stages of human development prior to the first cells becoming specialized, stem cells develop best in a low oxygen environment. As the embryo grows and the stem cells become specialized, they begin to require more oxygen. The more specialized the cell, the greater the oxygen required. With an increase in oxygen demand, there is also an increase in the number of mitochondria (energy producing cells) to convert the oxygen to ATP to support rapid cell division into new cells and tissue.

As the stem cells divide into more specialized cells, they are able to transform into new blood vessels, neurons, muscle, eye, pancreas, kidney, liver, bone marrow, etc., depending on the local tissue and growth factors present. 

Neurological Research

Research scientists have used stem cells from human umbilical cord blood on rats with induced strokes. They found that the stem cells would enter the brain, survive, change into new neurons, and improve the neurological function of the paralyzed animals. Case results that are similar are being reported for brain injured humans.

E.P. is a ten year old with cerebral palsy. She was born "dead", having suffered 28 minutes without sufficient oxygen. She is described as having extreme developmental delays and visual problems. She was given umbilical cord derived stem cells in November, 2002. She has since shown significant improvement in her ability to focus, concentrate and speak. Her vocabulary has expanded and she now uses complex sentences. Her articulation has improved so that strangers can now understand her. She can now hold a crayon, make a line, count to 24, feed herself, make jokes and interact with her siblings.

K.W. began suffering seizures when he was 3 months old which resulted in brain damage and severe developmental delays. He is now three years old. Within a month of receiving umbilical cord stem cells, his seizures stopped and his appetite and memory improved. Three months after treatment, there has been dramatic improvement in his eye/hand coordination. He is able to roll from his back to tummy, flex his fingers, sleep through the night (without waking up and crying), and is more curious about his surroundings. His verbal sounds and expressions have increased, his overall health has improved and he is a more active and happy child.

A.B. was legally blind in his left eye due to macular degeneration and complications of a stroke. His vision was 500/20. The left eye was red and swollen at the time of treatment in January, 2003 with certified umbilical cord derived stem cells administered in Mexico. In the past six months, A.B.’s vision has steadily improved and is now 50/20. 

Pre-Treatments

As effective as stem cells are, it appears that stem cell treatment can be more effective if factors that kill or injure the stem cells are reduced as much as possible before the injections.

  1. Stem cells "home" to areas of inflammation and low oxygen levels usually seen in injured and diseased tissue. If a person has infections and inflammation throughout the body, the stem cells will migrate to multiple areas. These diversions can slow the process of recovery in a specific target organ. K.C. has diabetes and several infections. She received umbilical cord stem cells outside the U.S. for diabetic retinopathy. Two months after the treatment, her other infections were gone but she was still having challenges with her vision. Secondary infections and inflammations should therefore be treated before stem cell therapy to maximize the benefits to target organs and tissues.

  2. Heavy metals such as lead, cadmium, mercury, arsenic, etc. are toxic to stem cells and should be reduced as much as possible. The DMSA challenge test (**) can be used to ascertain the level of heavy metals in the system. Heavy metals are associated with increased damage to neurons. Heavy metals are also associated with a poor clinical outcome for both conventional and alternative treatments and removing the heavy metals improves the treatment results.

  3. Leaky gut syndrome and gut dysbiosis (bacteria overgrowth) should be treated to prevent endotoxins from entering the body and destroying the stem cells.

The cleaner and healthier the body can be made prior to the application of the stem cells, the better the results.

Improvements following stem cell therapy begin to appear in some cases within 2 to 3 weeks but most people begin to see results within three to six months, which can continue for up to a year.

Post-Treatment

After the stem cell treatment, the patient needs the assistance of family, friends and caregivers to continue to reduce emotional and physical stress as much as possible.

  1. Stress-induced glucocorticoids from the adrenal glands stimulate excitatory neurotransmitters, such as glutamate and aspartate, that can kill off stem cells and new neurons.

  2. Food and beverages high in sugar should be avoided for similar reasons. They can cause a hypoglycemic effect that triggers a stress response.

  3. Stem cell patients should avoid tobacco products for at least the first six months after stem cell treatment. Tobacco is a source of heavy metal contamination and free radical damage.

  4. Patients should avoid alcohol for at least six months after stem cell treatment. Alcohol contributes to a "leaky gut", inhibits nerve growth factor and is toxic to new neurons. We also recommend grape juice instead of red wine.

  5. Patients should avoid steroids (such as glucocosteroids for immune suppression) and medications containing opiates as much as possible. Grains, including rice and breads, have opiate effects that are associated with nitric oxide stimulation and neurotoxicity.

More research is needed in this area but preliminary reports suggest that slower improvements are made in patients on predominantly grain diets. 

Neuroprotectant Foods and Supplements

There are patients who see the glass as half full. These patients seem to be improving more quickly with stem cell treatments. There are those who not only see the glass as half empty, they see an ugly old glass, the water inundated with germs, and the glass too far out of reach. These people need greater supervised care through the first few months after stem cell therapy to insure that they receive fresh organic foods, daily supplements, intravenous antioxidant therapies, counseling, physical therapy, etc. There is some support for depression being a symptom of stem cell deficiency. Further research may also find that negative emotions (anger, irritation, "thinking the worst", etc.) are a symptom of an inability to repair and renew damaged cells.

While stem cells are engrafting, migrating, proliferating and differentiating, they need antioxidant protection to help them survive. This includes an "ORAC" (Oxygen Radical Absorbant Capacity or high antioxidant) diet as well as supplements. Foods that contain antioxidants can assist the mitochondria in pumping out enough energy (ATP) to protect neurons from toxic assaults. Vegetables high in antioxidants include kale, spinach, Brussels sprouts, alfalfa, broccoli, beets, red bell pepper, onions and corn. Fruits high in antioxidants include prunes, blueberries, blackberries, strawberries, raspberries, plums, oranges, red grapes, cherries, kiwi and grapefruit. These fruits can be eaten with other foods such as plain yogurt to slow their digestion.

Antioxidant seasonings include curcumin (curry), ginger, natural vanilla flavoring, garlic, Fenugreek, parsley, thyme, sage and rosemary.

Glutathione protects cells and neurons against oxyradical damage and is associated with improvement in function after brain injury. Factors that increase and have a sparing effect on glutathione include vitamin D3, Fenugreek, fiboflavin, aloe vera, ginger, garlic, vitamin E, Ginkgo biloba, pycnogenol, green tea, succinate, citrate and natural vitamin C.

Preparing the Ground Work

Pioneering work is now being done in other countries using stem cells separated and expanded from certified (absence of disease) umbilical cord blood. Ten patients with various health problems have recently received injections or infusions of this stem cell cocktail. No immune suppressive treatments were used and there have been little or no side effects reported.

 

For further information on umbilical cord-derived stem cell therapies, go to http://www.stemcelltherapies.org.

** DMSA Tests available from:

Doctor’s Data, Chicago, Illinois, phone: 800-323-2784, http://www.DoctorsData.com
Metametrix Clinical Laboratory, 800-221-4640, http://www.metametrix.com
King James Laboratory, 800-437-1404, http://www.kingjamessomegatech-lab.com/serv02.htm.

 

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