title: Human adipose-derived mesenchymal stem cells improve motor functions and are neuroprotective in the 6-hydroxydopamine-rat model for Parkinson's disease when cultured in monolayer cultures but suppress hippocampal neurogenesis and hippocampal memory function when cultured in spheroids.
abstract: Adult human adipose-derived mesenchymal stem cells (MSC) have been reported to induce neuroprotective effects in models for Parkinson's disease (PD). However, these effects strongly depend on the most optimal application of the transplant. In the present study we compared monolayer-cultured (aMSC) and spheroid (sMSC) MSC following transplantation into the substantia nigra (SN) of 6-OHDA lesioned rats regarding effects on the local microenvironment, degeneration of dopaminergic neurons, neurogenesis in the hippocampal DG as well as motor and memory function in the 6-OHDA-rat model for PD. aMSC transplantation significantly increased tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF) levels in the SN, increased the levels of the glial fibrillary acidic protein (GFAP) and improved motor functions compared to untreated and sMSC treated animals. In contrast, sMSC grafting induced an increased local microgliosis, decreased TH levels in the SN and reduced numbers of newly generated cells in the dentate gyrus (DG) without yet affecting hippocampal learning and memory function. We conclude that the neuroprotective potential of adipose-derived MSC in the rat model of PD crucially depends on the applied cellular phenotype.
authors.affiliation: Department of Neurology, Charité University Medicine Berlin, CCM, Charitéplatz 1, D-10117, Berlin, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Berg
authors.forename: Manfred
authors.initials: M
authors.lastname: Roch
authors.forename: Jennifer
authors.initials: J
authors.lastname: Altschüler
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
authors.forename: Anne
authors.initials: A
authors.lastname: Schwerk
authors.forename: Andreas
authors.initials: A
authors.lastname: Kurtz
authors.forename: Barbara
authors.initials: B
authors.lastname: Steiner
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008568:Memory / Q000502:physiology*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018613:Microscopy, Confocal; D009043:Motor Activity / Q000502:physiology*; D055495:Neurogenesis; D000066829:Neuroprotection / Q000502:physiology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology* / Q000628:therapy; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase