Biomedical subjects

Massimo Corbo

Publications and source records attributed to Massimo Corbo.

4 recordsLinked to original sources

PubMed2005

Production of monocyte chemoattractant protein-1 in amyotrophic lateral sclerosis.

The presence of activated microglia in the spinal cord of amyotrophic lateral sclerosis (ALS) patients is usually accompanied by inflammatory biochemical changes, but these are largely unexplored. Monocyte chemoattractant protein-1 (MCP-1) is critical for recruitment of inflammatory cells of monocytic lineage after inflammation or injury to the central nervous system. MCP-1 concentrations were measured by an enzyme-linked immunosorbent assay in the cerebrospinal fluid (CSF) and the serum of 27 patients with ALS and 30 patients with noninflammatory neurological diseases. In ALS, circulating MCP-1 levels were significantly increased in the serum and particularly in the CSF. Immunoreactivity for MCP-1 in ALS spinal cord was detected mostly in astrocytes but also in microglia, neurons, and within the vasculature of the cord. Our findings suggest a role for MCP-1 as an important molecular mediator of the injury response in ALS.

Amyotrophic Lateral Sclerosis↗

PubMed2004

Stem cell therapy for neurodegenerative diseases: the issue of transdifferentiation.

In the past few years research on stem cells has exploded as a tool to develop potential therapies to treat incurable neurodegenerative diseases. Stem cell transplantation has been effective in several animal models, but the underlying restorative mechanisms are still unknown. Several events such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation (adult cell acquisition of new unexpected identities) may explain therapeutic success, in addition to replacement of lost cells. This issue needs to be clarified further to maximize the potential for effective therapies. Preliminary stem transplantation trials have already been performed for some neurodegenerative diseases. There is no effective pharmacological treatment for amyotrophic lateral sclerosis, but recent preliminary data both in experimental and clinical settings have targeted it as an ideal candidate disease for the development of stem cell therapy in humans. This review summarizes recent advances gained in stem cell research applied to neurodegenerative diseases with a special emphasis to the criticisms put forward.

Animals↗

PubMed2004

Cell-replacement therapy with stem cells in neurodegenerative diseases.

In the past few years, research on stem cells has expanded greatly as a tool to develop potential therapies to treat incurable neurodegenerative diseases. Stem cell transplantation has been effective in several animal models, but the underlying restorative mechanisms are still unknown. Several mechanisms such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation may explain positive therapeutic results, in addition to replacement of lost cells. The biological issue needs to be clarified in order to maximize the potential for effective therapies. The absence of any effective pharmacological treatment and preliminary data both in experimental and clinical settings has recently identified Amyotrophic Lateral Sclerosis (ALS) as an ideal candidate disease for the development of stem cell therapy in humans. Preliminary stem transplantation trials have already been performed in patients. The review discusses relevant topics regarding the application of stem cell research to ALS but in general to other neurodegenerative diseases debating in particular the issue of transdifferentiation, endogenous neural stem cell, and factors influencing the stem cell fate.

Amyotrophic Lateral Sclerosis↗

PubMedDate not supplied

Stem-cell therapy for amyotrophic lateral sclerosis.

CONTEXT: With the lack of effective drug treatments for amyotrophic lateral sclerosis (ALS), and compelling preclinical data, stem-cell research has highlighted this disease as a candidate for stem-cell treatment. Stem-cell transplantation is an attractive strategy for neurological diseases and early successes in animal models of neurodegnerative disease generated optimism about restoring function or delaying degeneration in human beings. The restricted potential of adult stem cells has been challenged over the past 5 years by reports on their ability to acquire new unexpected fates beyond their embryonic lineage (transdifferentiation). Therefore, autologous or allogeneic stem cells, undifferentiated or transdifferentiated and manipulated epigenetically or genetically, could be a candidate source for local or systemic cell-therapies in ALS. STARTING POINT: Albert Clement and colleagues (Science 2003; 302: 113-17) showed that in SOD1G93A chimeric mice, motorneuron degeneration requires damage from mutant SOD1 acting in non-neuronal cells. Wild-type non-neuronal (glial) cells could delay degeneration and extend survival of mutant-expressing motorneurons. Letizia Mazzini and colleagues (Amyotroph Lateral Scler Other Motor Neuron Disord 2003; 4: 158-61) injected autologous bone-marrow-derived stem cells into the spinal cord of seven ALS patients. These investigators reported that the procedure had a reasonable margin of clinical safety. WHERE NEXT? The success of cell-replacement therapy in ALS will depend a lot on preclinical evidence, because of the complexity and precision of the pattern of connectivity that needs to be restored in degenerating motoneurons. Stem-cell therapy will need to be used with other drugs or treatments, such as antioxidants and/or infusion of trophic molecules.

Adult↗