Intracerebral transplantation of dopaminergic (DA) cells is currently further explored as a potential restorative therapy for Parkinson's disease (PD). However, before they can be considered for a more widespread clinical use a number of critical issues have to be resolved, including an optimized transplantation protocol. This study has been performed in a rat 6-hydroxydopamine model of PD and is based on the microtransplantation approach. The results demonstrate a reduced survival (threefold) for a single cell suspension of E14 rat ventral mesencephalon compared to a fragment suspension when a metal cannula is used for implantation. However, fragment suspensions result in a more variable graft survival and ectopically placed cells along the implantation tract. When a glass capillary is used for implantation, the survival of the single cell suspension (so-called "micrograft") improved by fourfold (vs. single cells/metal cannula) and is superior to the combination of the metal cannula and fragment suspension (+40%). The micrografts show a reduced variability in DA neuron survival as well as fewer ectopically placed cells. Moreover, the implantation time can significantly be reduced from 19 to 7 min in micrografted animals without a compromise in DA graft survival and functional behavioral outcome. Using the microtransplantation approach graft size can be tailored effectively by varying the density of the final cell suspension at least between 11,000 and 320,000 cells/microl, resulting in comparable survival of tyrosine hydroxylase (TH)-positive neurons in the range of 2-4%. With this approach no more than 100 surviving TH-positive neurons are necessary to produce functional effects in the amphetamine-induced rotation test. Interestingly, we found that DA micrografts into lesion striatum present 20% higher survival rates of TH neurons in comparison to the intact striatum. In summary, these results provide further evidence for the usefulness of the microtransplantation approach and allow for a more precise and tailored adaptation of the implantation parameters for further studies on DA, and possibly also other neural-, glial-, and stem cell-derived grafts.
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http://dx.doi.org/10.3727/096368909788341324 | DOI Listing |
Ther Adv Hematol
January 2025
Center of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) stands as a cornerstone in the treatment of hematological malignancies, recognized for its remarkable efficacy. However, the persistent challenge of graft-versus-host disease (GVHD) continues to represent a significant barrier, often being the leading cause of nonrelapse mortality after allo-HSCT. To address this limitation, hematopoietic stem cell microtransplantation (MST) has emerged as a novel therapeutic strategy that synergistically combines chemotherapy, allo-HSCT, and cellular immunotherapy.
View Article and Find Full Text PDFMembranes (Basel)
March 2024
Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, Italy.
Among the most prevalent neurological disorders, epilepsy affects about 1% of the population worldwide. We previously found, using human epileptic tissues, that GABAergic neurotransmission impairment is a key mechanism that drives the pathological phenomena that ultimately lead to generation and recurrence of seizures. Using both a "microtransplantation technique" and synaptosomes preparations from drug-resistant temporal lobe epilepsies (TLEs), we used the technique of two-electrode voltage clamp to record GABA-evoked currents, focusing selectively on the synaptic "fast inhibition" mediated by low-affinity GABA receptors.
View Article and Find Full Text PDFLife (Basel)
December 2022
Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, Italy.
Membranes (Basel)
October 2022
Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, Apdo 99, E-03080 Alicante, Spain.
The use of oocytes in electrophysiological and biophysical research constitutes a long and successful story, providing major advances to the knowledge of the function and modulation of membrane proteins, mostly receptors, ion channels, and transporters. Earlier reports showed that these cells are capable of correctly expressing heterologous proteins after injecting the corresponding mRNA or cDNA. More recently, the oocyte has become an outstanding host-cell model to carry out detailed studies on the function of fully-processed foreign membrane proteins after their microtransplantation to the oocyte.
View Article and Find Full Text PDFJ Vis Exp
July 2022
The Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch;
Excitatory and inhibitory ionotropic receptors are the major gates of ion fluxes that determine the activity of synapses during physiological neuronal communication. Therefore, alterations in their abundance, function, and relationships with other synaptic elements have been observed as a major correlate of alterations in brain function and cognitive impairment in neurodegenerative diseases and mental disorders. Understanding how the function of excitatory and inhibitory synaptic receptors is altered by disease is of critical importance for the development of effective therapies.
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