Intranigral Transplantation of Epigenetically Induced BDNF-Secreting Human Mesenchymal Stem Cells: Implications for Cell-Based Therapies in Parkinson's Disease

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dc.contributor.authorSomoza, Rodrigo
dc.contributor.authorJuri, Carlos
dc.contributor.authorBaes, Mauricio
dc.contributor.authorWyneken, Ursula
dc.contributor.authorJavier Rubio, Francisco
dc.date.accessioned2024-01-10T12:06:11Z
dc.date.available2024-01-10T12:06:11Z
dc.date.issued2010
dc.description.abstractIt is thought that the ability of human mesenchymal stem cells (hMSC) to deliver neurotrophic factors might be potentially useful for the treatment of neurodegenerative disorders. The aim of the present study was to characterize signals and/or molecules that regulate brain-derived neurotrophic factor (BDNF) protein expression/delivery in hMSC cultures and evaluate the effect of epigenetically generated BDNF-secreting hMSC on the intact and lesioned substantia nigra (SN). We tested 4 different culture media and found that the presence of fetal bovine serum (FBS) decreased the expression of BDNF, whereas exogenous addition of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) to serum-free medium was required to induce BDNF release (125 +/- 12 pg/day/10(6) cells). These cells were called hM(N)SC. Although the induction medium inhibited the expression of alpha smooth muscle actin (ASMA), an hMSC marker, and increased the nestin-positive subpopulation of hMSC cultures, the ability to express BDNF was restricted to the nestin-negative subpopulation. One week after transplantation into the SN, the human cells integrated into the surrounding tissue, and some showed a dopaminergic phenotype. We also observed the activation of Trk receptors for neurotrophic factors around the implant site, including the BDNF receptor TrkB. When we transplanted these cells into the unilateral lesioned SN induced by striatal injection of 6-hydroxydopamine (6-OHDA), a significant hypertrophy of nigral tyrosine hydroxylase (TH)(+) cells, an increase of striatal TH-staining and stabilization of amphetamine-induced motor symptoms were observed. Therefore, h MSC cultures exposed to the described induction medium might be highly useful as a vehicle for neurotrophic delivery to the brain and specifically are strong candidates for future therapeutic application in Parkinson's disease.
dc.description.funderFundacion Andes
dc.description.funderUniversidad del Desarrollo
dc.description.funderAnillo
dc.fechaingreso.objetodigital19-04-2024
dc.format.extent11 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.bbmt.2010.06.006
dc.identifier.eissn1523-6536
dc.identifier.issn1083-8791
dc.identifier.pubmedidMEDLINE:20542127
dc.identifier.urihttps://doi.org/10.1016/j.bbmt.2010.06.006
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76126
dc.identifier.wosidWOS:000283830800004
dc.information.autorucMedicina;Juri C;S/I;7476
dc.issue.numero11
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final1540
dc.pagina.inicio1530
dc.publisherELSEVIER SCIENCE INC
dc.revistaBIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
dc.rightsacceso restringido
dc.subjectMesenchymal stem cell transplantation
dc.subjectNeurotrophins
dc.subjectTrk receptors
dc.subjectSubstantia nigra
dc.subjectUnilateral 6-hydroxydopamine lesion
dc.subjectMARROW STROMAL CELLS
dc.subjectBONE-MARROW
dc.subjectNEUROTROPHIC FACTOR
dc.subjectDOPAMINERGIC-NEURONS
dc.subjectSUBSTANTIA-NIGRA
dc.subjectTYROSINE-HYDROXYLASE
dc.subjectCEREBRAL-ISCHEMIA
dc.subjectNEURAL PROGENITOR
dc.subjectGROWTH-FACTOR
dc.subjectADULT-RAT
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleIntranigral Transplantation of Epigenetically Induced BDNF-Secreting Human Mesenchymal Stem Cells: Implications for Cell-Based Therapies in Parkinson's Disease
dc.typeartículo
dc.volumen16
sipa.codpersvinculados7476
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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