Cerebral Palsy and Regenerative Medicine ©

By David Steenblock, M.S., D.O.

"The obstacle is the path." Zen Proverb

Umbilical cord blood stem cells have the ability, when stimulated by neural growth factors, to produce neural and glial cells (Bicknese, 2002). Cord blood cells treated with retinoic acid and nerve growth factor have been shown to respond by transforming into cells that have the markers of neurons and glia. Umbilical cord blood appears to be more versatile than previously thought and has therapeutic potential for replacing damaged brain cells and providing a vehicle for gene delivery in neurodegenerative diseases, trauma, and genetic disorders. (Sanchez-Ramos, 2001).

The CD133 subset of CD34+ stem cells spontaneously transform to neural stem cells in the laboratory and are included (85%) in the stem cell injections used by Stem Cell Therapies, Inc.

Graft-versus Host Disease

While whole cord blood produces significantly less graft-versus-host disease (GVHD) than transplantations with bone marrow or adult hematopoietic cells (Rubinstein, 1998; Gluckman, 1997; Kurtzberg 1996; Wagner, 1996; Wadhwa, 2002), there is still some risk, though significantly reduced, of transfusion reactions in ABO blood group incompatibility (Pahwa, 1994). Because of this small risk when using whole umbilical cord blood, Stem Cell Therapies, Inc. has procured pure CD34+ cells for experimental use.

Purity

Stem Cell Therapies, Inc. has acquired extremely purified Umbilical Cord Stem Cells composed entirely of CD34+ cells, devoid of red and white blood cells. This freedom from more mature immune cells (especially CD47 – the “Self” immune defense cell) contributes to reduced risks of graft versus host complications, even with mismatched donors and recipients (Pettersen, 2000, Avice, 2000).

Augmentation

About 300,000 stem cells are generally isolated from one neonate’s umbilical cord and placenta blood. Injections used by Stem Cell Therapies, Inc. contain 1.5 million CD34+ cells. Studies with stem cell transplants demonstrate that increased numbers of CD34+ stem cells further promote successful and long term stem cell engrafting as well as little or no graft versus host disease complications (Handgritinger, 2001, Pecora, 2001).

Stem Cell Therapies, Inc. uses a proprietary method to obtain a pure culture of CD34+ cells. These CD34+ cells are the active stem cells contained in umbilical cord blood that are able to reconstitute the chemotherapy and/or radiation depleted bone marrow and are multipotent for the growth of other tissues types.

Acute Injury and Stem Cell Homing Mechanisms

Recent studies have clarified to a large degree the mechanisms underlying the normal residence of endogenous bone marrow stem cells in a quiescent state and their proliferation, mobilization and homing to injured tissues (Rabbany, 2003).

Endogenous stem cells are necessary for tissue revascularization, wound healing, and organ regeneration. Tissue specific stem cells reside in the bone marrow in specific niches where they are maintained in an undifferentiated and quiescent state.

When a tissue is injured, VEGF (Vascular Endothelial Growth Factor) is produced and stimulates endothelial cells that line the blood vessel walls, to move to the site of injury to begin the process of forming new blood vessels (angiogenesis). Other growth factors are also involved. At the site of the injury, blood vessels have disrupted basement membranes and express a number of chemical signals that attract and hold platelets, white blood cells and recently mobilized stem cells. A chemical called “Stromal derived Factor-1” helps mobilize the stem cells and creates a protective “niche” within the web of the extracellular matrix (Hattori, 2003). The stem cells multiply and are stimulated by other factors (E-selectin ligands in cooperation with alpha4 integrin or P-selectin ligands) that assist in “homing” to the areas of inflammation (Katayama, 2003).

One of the strongest promoters of stem cell expansion in laboratory tests is endothelial cells. When cord blood stem cells are mixed with endothelial cells, there is a 640-fold increase in the number of CD34+ progenitor cells (Rosler, 2000). This degree of proliferation is significantly higher than numbers found with other growth factors. The release of endothelial cells into the blood stream and/or from the blood vessel walls at the time of injury are considered likely events in stimulating stem cell proliferation at the injured site.

The approximately 300,000 cells obtained from each placenta and cord unit are expanded to a standard amount of 1.5 million viable cells. Various growth factors can be used for this expansion of stem cells. In a study by Katayama, cord blood stem cells were expanded in the laboratory using stem cell growth factor, interleukin-3, interleukin-6, granulocyte colony stimulating factor and erythropoietin and the cells retained their normal chromosome arrangements. This demonstrated that expansion of cord blood stem cells did not produce abnormal stem cells (Katayama, 2001).

Safety

In a stem cell transplantation study by McKeena in 2002, 59 patients (age: mean 27 years, range, 4 months - 59 years) were transplanted with a total of 82 unrelated units of umbilical cord blood. Diagnoses included, AML (19), NHL (12), ALL (7), and 13 additional malignant and nonmalignant diseases. All patients received i.v. hydration and acetaminophen and diphenhydramine as premedication, and most were administered antiemetics. Some patients experienced a mild reaction. No moderate/severe reactions occurred. Reaction types and rates were as follows: hypertension (24%), nausea (10%), vomiting (5%), unusual taste/smell (5%), headache (5%), bradycardia (2%), cough (2%), back (2%) or abdominal (2%) pain, and transient, asymptomatic desaturation (2%). In several cases, similar symptoms were present in the days prior to and/or after infusion, making the association with UCB uncertain. No patients experienced fever, or chills, flushing, hives, dyspnea/broncospasm, or chest pain. No clinical or laboratory evidence of hemolysis was apparent. Overall, UCB infusions are safe and well-tolerated with all reported reactions being mild and easily managed, even with the use of strong medications (McKeena, 2003). Because the stem cells in our research are separated from the blood, purified stem cell therapies have even less side effects than cord blood therapies and strong immune suppressive medications, that are also toxic to stem cells, are not needed.

For about the first month after stem cell therapy, the patient may need to sleep and rest a great deal. During this time, the stem cells are grafting into the extracellular matrix, creating a stable niche in which to grow and proliferate. Generally, sometime in the second month, there is an increase in energy, muscle tone and stamina. The stem cells move from their niches and migrate through the bloodstream to areas of inflammation and injury. Hypoxic (lack of oxygen) niches adjacent to blood vessels are needed for stem cell growth but areas of normal oxygen concentrations are needed for stem cell differentiation. Specialized cell function requires oxygen, and mild hyperbaric treatments (1.2-1.5 ATA, breathing 21% oxygen) may be more stem cell friendly than higher pressures (2.0 ATA) and concentrations (100% oxygen) for stem cell differentiation into neurons and glia cells.

For Stem Cell Research References Click Here!