Neurological disorders and the potential role for stem cells as a therapy.

Introduction Neurological disorders are routinely characterized by loss of cells in response to an injury or a progressive insult. Stem cells could therefore be useful to treat these disorders. Sources of data Pubmed searches of recent literature. Areas of agreement Stem cells exhibit proliferative capacity making them ideally suited for replacing dying cells. However, instead of cell replacement therapy stem cell transplants frequently appear to work via neurotrophic factor release, immunomodulation and upregulation of endogenous stem cells. Areas of controversy and areas timely for developing research Many questions remain with respect to the use of stem cells as a therapy, the answers to which will vary depending on the disorder to be treated and mode of action. Whereas the potential tumorigenic capability of stem cells is a concern, most studies do not support this notion. Further determination of the optimal cell type, and whether to perform allogeneic or autologous transplants warrant investigation before the full potential of stem cells can be realized. In addition, the use of stem cells to develop disease models should not be overlooked.

The treatment of neurodegenerative disorders using umbilical cord blood and menstrual blood-derived stem cells.

Stem cell transplantation is a potentially important means of treatment for a number of disorders. Two different stem cell populations of interest are mononuclear umbilical cord blood cells and menstrual blood-derived stem cells. These cells are relatively easy to obtain, appear to be pluripotent, and are immunologically immature. These cells, particularly umbilical cord blood cells, have been studied as either single or multiple injections in a number of animal models of neurodegenerative disorders with some degree of success, including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and Sanfilippo syndrome type B. Evidence of anti-inflammatory effects and secretion of specific cytokines and growth factors that promote cell survival, rather than cell replacement, have been detected in both transplanted cells.

Human umbilical cord blood cell grafts for brain ischemia.

Irreversible and permanent damage develop immediately adjacent to the region of reduced cerebral blood perfusion in stroke patients. Currently, the proven thrombolytic treatment for stroke, tissue plasminogen activator, is only effective when administered within 3 h after stroke. These disease characteristics should be taken under consideration in developing any therapeutic intervention designed to widen the narrow therapeutic range, especially cell-based therapy. Over the past several years, our group and others have characterized the therapeutic potential of human umbilical cord blood cells for stroke and other neurological disorders using in vitro and vivo models focusing on the cells' ability to differentiate into nonhematopoietic cells including neural lineage, as well as their ability to produce several neurotrophic factors and modulate immune and inflammatory reaction. Rather than the conventional cell replacement mechanism, we advance alternative pathways of graft-mediated brain repair involving neurotrophic effects resulting from release of various growth factors that afford cell survival, angiogenesis, and anti-inflammation. Eventually, these multiple protective and restorative effects from umbilical cord blood cell grafts may be interdependent and act in harmony in promoting therapeutic benefits for stroke.

From the basics to application of cell therapy, a steppingstone to the conquest of neurodegeneration: a meeting report.

The annual meeting of the American Society for Neural Therapy and Repair (ASNTR) showcases the latest research trends in neurodegenerative disease and the related medical regenerative science. The 2008 ASNTR meeting covered a variety of different topics ranging from basic research to exploration of currently unknown pathogenesis and mechanisms for specific neurodegenerative disease such as Parkinson's disease, Alzheimer's disease, or stroke. This included studies to characterize stem cells, such as neural stem cells, embryonic stem cells, bone marrow mesenchymal stem cells, and human umbilical cord blood cells, for transplantation and the conditions necessary to maximize the efficacy of endogenous and exogenous stem cells, such as isolation, purification, differentiation, and migration. Moreover, a number of studies looked at methods for more advanced application of transplantation of cells or specific factors, through tissue engineering or manipulation beyond simple injection. Finally, well-known or previously un-known dietary supplementation or pharmacological materials that can affect the nervous system positively or negatively, were also important topics.

Refractory angina cell therapy (ReACT) involving autologous bone marrow cells in patients without left ventricular dysfunction: a possible role for monocytes.

Autologous bone marrow mononuclear cell (BMMC) transplantation has emerged as a potential therapeutic option for refractory angina patients. Previous studies have shown conflicting myocardium reperfusion results. The present study evaluated safety and efficacy of CellPraxis Refractory Angina Cell Therapy Protocol (ReACT), in which a specific BMMC formulation was administered as the sole therapy for these patients. The phase I/IIa noncontrolled, open label, clinical trial, involved eight patients with refractory angina and viable ischemic myocardium, without left ventricular dysfunction and who were not suitable for conventional myocardial revascularization. ReACT is a surgical procedure involving a single series of multiple injections (40-90 injections, 0.2 ml each) into ischemic areas of the left ventricle. Primary endpoints were Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at 18 months follow-up and myocardium ischemic area reduction (assessed by scintigraphic analysis) at 12 months follow-up, in correlation with a specific BMMC formulation. Almost all patients presented progressive improvement in angina classification beginning 3 months (p = 0.008) postprocedure, which was sustained at 18 months follow-up (p = 0.004), as well as objective myocardium ischemic area reduction at 12 months (decrease of 84.4%, p < 0.004). A positive correlation was found between monocyte concentration and CCSAC improvement (r = -0.759, p < 0.05). Improvement in CCSAC, followed by correlated reduction in scintigraphic myocardium ischemic area, strongly suggests neoangiogenesis as the main stem cell action mechanism. The significant correlation between number of monocytes and improvement strongly supports a cell-related effect of ReACT. ReACT appeared safe and effective.