PMID- 25120226 OWN - NLM STAT- MEDLINE DCOM- 20151204 LR - 20211021 IS - 2629-3277 (Electronic) IS - 2629-3277 (Linking) VI - 11 IP - 1 DP - 2015 Feb TI - 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. PG - 133-49 LID - 10.1007/s12015-014-9551-y [doi] AB - 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. FAU - Berg, Jurgen AU - Berg J AD - Department of Neurology, Charite University Medicine Berlin, CCM, Chariteplatz 1, D-10117, Berlin, Germany. FAU - Roch, Manfred AU - Roch M FAU - Altschuler, Jennifer AU - Altschuler J FAU - Winter, Christine AU - Winter C FAU - Schwerk, Anne AU - Schwerk A FAU - Kurtz, Andreas AU - Kurtz A FAU - Steiner, Barbara AU - Steiner B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Stem Cell Rev Rep JT - Stem cell reviews and reports JID - 101752767 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Glial Fibrillary Acidic Protein) RN - 8HW4YBZ748 (Oxidopamine) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) SB - IM MH - Adipose Tissue/cytology MH - Adult MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cell Culture Techniques/*methods MH - Cell Differentiation/genetics MH - Cells, Cultured MH - Disease Models, Animal MH - Female MH - Glial Fibrillary Acidic Protein/genetics/metabolism MH - Hippocampus/cytology/*physiology MH - Humans MH - Memory/*physiology MH - Mesenchymal Stem Cell Transplantation/methods MH - Mesenchymal Stem Cells/cytology/metabolism/*physiology MH - Microscopy, Confocal MH - Motor Activity/*physiology MH - Neurogenesis MH - Neuroprotection/physiology MH - Oxidopamine MH - Parkinsonian Disorders/chemically induced/*physiopathology/therapy MH - Rats, Wistar MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transplantation, Heterologous MH - Tyrosine 3-Monooxygenase/genetics/metabolism EDAT- 2014/08/15 06:00 MHDA- 2015/12/15 06:00 CRDT- 2014/08/15 06:00 PHST- 2014/08/15 06:00 [entrez] PHST- 2014/08/15 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - 10.1007/s12015-014-9551-y [doi] PST - ppublish SO - Stem Cell Rev Rep. 2015 Feb;11(1):133-49. doi: 10.1007/s12015-014-9551-y.