School of Medicine, emphasis was placed on high doses of CD34+bone marrow mononuclear cells (BMMNCs) given to patients after undergoing coronary stenting. At six month’s follow-up, there was a mean improvement (4.5 percent) of ejection fraction, or how much blood the heart is able to pump from the left ventricle (most commonly), in patients who had received at least 10 million cells compared to the low dose group (5 × 108) and control. A randomized, controlled, Phase II, double-blind trial conducted by the University of Texas at Houston evaluated the safety and efficacy of autologous BMMNCs under electromechanical guidance for patients with chronic ischemia (lack of oxygen) heart disease and left ventricular dysfunction. No significant change was observed for any of the parameters of the treatment group compared to control.
Peripheral artery disease, in which the patient has damaged arteries and surrounding tissue due to an obstruction, is also an area of intensive research. Bone marrow-derived and endothelial progenitor cells have been harvested from patients with or without G-CSF mobilization; target cell population(s) are amplified and injected into the patient’s affected limb (usually multiple injection sites around the damaged tissue). Results have been mixed for improved perfusion of the damaged tissue, but collateral growth (new blood vessel growth), increased walking time, and overall limb salvage has been observed in several recent small clinical trials.
Potential Therapies in Regenerative Medicine
In a study by Stessuk and colleagues (2013) in Brazil, it was reported that autologous BMMNCs were administered to four patients with advanced-stage chronic obstructive pulmonary disease, refractory to standard treatments, and limited life expectancy. Baseline spirometry measurements, a measure of lung capacity, were taken prior to baseline. Measurements were retaken at six months follow-up, and the patients were asked about quality of life. It was concluded that improved lung capacity was observed in three of the four patients. Larger studies are now being conducted exploring the potential use of these cells to improve lung capacity and quality of life for several lung disorders and even lung transplant recipients.
Promising research in the area of type 1 diabetes (T1D) is focused on autologous blood stem cells to replenish damaged β-cells. However, even when there is an increase in growth of β-cells, the subject’s immune system continues to attack the new healthy cells. Dr. Habib Zaghouani’s group at the University of Missouri developed Ig-GAD2, a drug designed to inhibit the autoimmune attack on β-cells while simultaneously infusing autologous bone marrow stem cells, which has shown promise in a murine model. During this research, he and his team discovered the administration of the drug and stem cells encouraged the growth of new blood vessels in the pancreas, which helped the β-cells proliferate and thrive. He concluded that β-cells indirectly require new blood vessels in order to continue to grow. A pilot study performed at the University of Florida showed that infusion of cord blood stem cells provided some slowing of the loss of insulin production in children with T1D, evidenced by the reduced need for insulin injections.
Diseases such as Alzheimer’s, for which human cord blood MSCs have been used in animal models, show a reduction of beta amyloid and are currently being investigated in human trials. Neurodegenerative diseases, such as Parkinson’s disease and spinal cord injury, can potentially benefit from use of mesenchymal stem cells. Laboratory studies on cord blood MSCs have shown benefits for liver cirrhosis via enhanced wound healing. Preliminary study results indicate that an infusion of cord blood MSCs promotes the secretion of glucose and insulin, which help improve liver function. Many more uses of cord blood MSCs are being investigated, including bone repair and treatment of congenital heart defects and peripheral arterial occlusive disease.
Given the recent positive results from a large portion of these preclinical and small clinical studies, it is reasonable to state that once the treatment protocols that entail optimum dosage of stem cells, improved identification and isolation methods of the stem cells, and timing and location of administration are standardized, utilization of blood or bone marrow-derived stem cells will be an effective adjunct therapy. In order to demonstrate true efficacy it is also necessary to conduct adequately powered, multicenter, randomized, controlled clinical trials.
Mandy M. McBroom
University of Texas Southwestern Medical Center
See Also: Adult Stem Cells: Overview; Clinical Trials, U.S.: Graft Failure, Graft-Versus-Host Disease; Mesenchymal Stem Cells.
Further Readings
Ambinder, R. F., “The Same but Different: Autologous Hematopoietic Stem Cell Transplantation for Patients With Lymphoma and HIV Infection.” Bone Marrow Transplant, v.44/1 (2009).
Haller, M. J., et al. “Autologous Umbilical Cord Blood Infusion for Type 1 Diabetes,” Experimental Hematology, v.36/6 (2008).
Jung, K. H., et al. “Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Improve Glucose Homeostasis in Rats With Liver Cirrhosis.” International Journal of Oncology, v.39/1 (2011).
Kang, Y. H., et al. “Transplantation of Porcine Umbilical Cord Matrix Mesenchymal Stem Cells in a Mouse Model of Parkinson’s Disease.” Journal of Tissue Engineering and Regenerative Medicine, v.7 (2011).
Kim, A. K., et al. “Stem-Cell Therapy for Peripheral Artery Occlusive Disease.” European Journal of Vascular and Endovascular Surgery, v.42/5 (2011).
Kim, J. Y., et al. “Soluble Intracellular Adhesion Molecule-1 Secreted by Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Reduces Amyloid-Plaques.” Cell Death Differ, v.19/4 (2012).
Liao, Y. H., et al. “Adult Stem or Progenitor Cells in Treatment for Type I Diabetes.” Canadian Journal of Surgery, v.50/2 (2007).
Lin, Y. C., et al. “Human Umbilical Mesenchymal Stem Cells Promote Recovery After Ischemic Stroke.” Stroke, v.42/7 (2011).
Liu, Y., et al. “Therapeutic Potential of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Rheumatoid Arthritis.” Arthritis Research and Therapy, v.12/6 (2010).
Longhini-dos-Santos, N., et al. “Cell Therapy With Bone Marrow Mononuclear Cells in Elastase-Induced Pulmonary Emphysema.” Stem Cell Reviews and Reports, v.9/2 (2013).
Smith, S., W. Neaves, S. Teitelbaum, D. A. Prentice, and G. Tarne. “Adult Versus Embryonic Stem Cells: Treatments.” Science, v.316/5830 (2007).
Sodian, R., et al. “Use of Human Umbilical Cord-Derived Progenitor Cells for Tissue-Engineered Heart Valves.” Annals of Thoracic Surgery, v.89/3 (2010).
Tark, K. C., et al. “Effects of Human Cord Blood Mesenchymal Stem Cells on Cutaneous Wound Healing in Lepr db Mice.” Annals of Plastic Surgery, v.65/6 (2010).
Blood Adult Stem Cell: Major Pathologies
Blood Adult Stem Cell: Major Pathologies
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Blood Adult Stem Cell: Major Pathologies
Before the turn of the 17th century, regeneration of human cells was considered a myth, a legend sired from Greek mythology of the titan Prometheus. The Greek god Zeus punished Prometheus by chaining him to a rock while an eagle ate at his liver every day, only to have it regenerate due to his immortality.
In
