PubMed · 14860423
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M CORDARO. 1951. [Tissue therapy].. https://pubmed.ncbi.nlm.nih.gov/14860423/
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Currently, the most important therapeutic approaches in the acute phase of ischemic stroke are focused on the restoration of regional cerebral blood flow, early admission to a stroke unit and the attempt to block, using neuroprotective drugs, the biochemical and metabolic changes involved in the 'ischemic cascade'. Treatment with rt-PA in the acute phase, although very effective, is still limited to a small number of patients and positive preclinical results of neuroprotective treatment have not, as yet, been endorsed in clinical trials. The remarkable lack of concordance between the positive results in experimental models and the negative results obtained in clinical trials has led to a change in attitude in the conduct of preclinical studies as well as to a modification of the design of clinical trials, with special attention being paid to patient selection criteria and clinical evaluation. Some neuroprotective drugs, such as citicoline, have shown some efficacy in subgroups of patients with cerebral infarction, even with a therapeutic window of up to 24 h, which would suggest a possible neurorestorative effect. Different degrees of functional recovery, weeks or months after the ischemic event, are currently observed in clinical practice and have been related to endogenous self-repair mechanisms. The growing understanding of the mechanisms involved in the phenomena of brain plasticity and their modulation, together with the possibility of restoring functional deficits by encouraging endogenous neurogenesis or by cell therapy, open up new directions in the treatment of stroke patients.
BACKGROUND: The human enteric nervous system (ENS) descends from migrating neural crest cells (NCC) and is structured into different plexuses embedded in the gastrointestinal tract wall. The development of this entity strongly depends on the supply of an appropriate support with trophic factors during organogenesis. The lack of important factors, such as glial cell line-derived neurotrophic factor, leads to severe disturbances in the ENS and, thus, to motility disorders in children. The isolation of neuronal precursor cells as well as their transplantation after expansion in vitro is therefore a hopeful new approach concerning all forms of dysganglionosis in children. METHODS: We therefore established a way to isolate and expand precursor cells from the developing and postnatal human ENS. Bowel samples were obtained from human fetuses and children (from the 9th week of gestation to 5 years postnatal). Myenteric plexus was isolated by enzymatical digestion and cultivated until spheroid aggregates, the so-called neurospheres, developed. These neurospheres could be differentiated and also be transplanted after dissociation into aganglionic bowel in vitro. RESULTS: Enteric neurospheres could be grown from different gestational ages, including postmortem material. Undifferentiated proliferating precursor cells were kept in culture for up to 72 days and could be differentiated in neurons and glial cells in vitro. CONCLUSION: The first results using isolated enteric neurospheres in aganglionic bowel are quite promising and are a basis to develop an appropriate cell therapy for all kinds of dysganglionosis, especially for cases where a surgical approach is not sufficient or not even possible.
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