PMID- 21256457 OWN - NLM STAT- MEDLINE DCOM- 20110309 LR - 20181201 IS - 1878-1810 (Electronic) IS - 1878-1810 (Linking) VI - 157 IP - 2 DP - 2011 Feb TI - Bone marrow stromal cells as replacement cells for Parkinson's disease: generation of an anatomical but not functional neuronal phenotype. PG - 56-63 LID - 10.1016/j.trsl.2010.11.001 [doi] AB - The focus of cell replacement therapies (CRTs) for Parkinson's disease has been on delivering dopamine-producing cells to the striatum. Fetal grafts have proven the feasibility of this approach, but an appropriate source of replacement cells has restricted the clinical translation. Bone marrow stromal cells (BMSCs) have been heralded as an ideal source of dopaminergic (DAergic) replacement cells, as they are viewed as ethically acceptable, easily procured, and readily expanded. It is known that they confer functional benefits, particularly in stroke models, through the release of neurotrophic factors, but their transdifferentiation into neurons is still under contention. We sought to evaluate the neuronal phenotype and functional capacity of adult rat BMSCs after exposure to a novel multistep in vitro differentiation protocol compared with cells exposed to other reported neuronal differentiation conditions. We employed a systematic, comprehensive method of assessment to determine the neuronal differentiation capacity of BMSCs. Our fluorescence-activated cell sorting, immunofluorescent and semiquantitative polymerase chain reaction results confirmed that undifferentiated BMSCs isolated based on their adherence to plastic are of mesenchymal origin and express a range of lineage markers. After exposure to preinduction and neuronal induction steps, BMSCs down-regulate markers of other lineages but fail, as assessed by patch clamp, to differentiate into functional neurons. Thus, for BMSCs to be considered a source of DAergic neuronal replacement cells, their ability to transdifferentiate terminally along a neuronal lineage first must be clarified before attempting to direct more complex specification process required for them to be used in Parkinson's-disease-focused CRTs. CI - Crown Copyright (c) 2011. Published by Mosby, Inc. All rights reserved. FAU - Thomas, Meghan G AU - Thomas MG AD - Parkinson's Centre, Edith Cowan University, Perth, Western Australia; School of Exercise Biomedical and Health Science, Edith Cowan University, Perth, Western Australia, Australia. m.thomas@ecu.edu.au FAU - Stone, Leah AU - Stone L FAU - Evill, Lauren AU - Evill L FAU - Ong, Syerna AU - Ong S FAU - Ziman, Mel AU - Ziman M FAU - Hool, Livia AU - Hool L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101205 PL - United States TA - Transl Res JT - Translational research : the journal of laboratory and clinical medicine JID - 101280339 SB - IM CIN - Transl Res. 2011 Feb;157(2):53-5. PMID: 21256456 MH - Animals MH - *Bone Marrow Cells/cytology/metabolism MH - *Bone Marrow Transplantation MH - Cell Differentiation MH - Cell Lineage MH - Female MH - Flow Cytometry MH - Fluorescent Antibody Technique MH - Mesenchymal Stem Cells/cytology MH - Neurons/cytology/metabolism/*physiology MH - Parkinson Disease/*therapy MH - Phenotype MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stromal Cells/cytology/metabolism/*transplantation EDAT- 2011/01/25 06:00 MHDA- 2011/03/10 06:00 CRDT- 2011/01/25 06:00 PHST- 2010/04/12 00:00 [received] PHST- 2010/11/04 00:00 [revised] PHST- 2010/11/04 00:00 [accepted] PHST- 2011/01/25 06:00 [entrez] PHST- 2011/01/25 06:00 [pubmed] PHST- 2011/03/10 06:00 [medline] AID - S1931-5244(10)00289-6 [pii] AID - 10.1016/j.trsl.2010.11.001 [doi] PST - ppublish SO - Transl Res. 2011 Feb;157(2):56-63. doi: 10.1016/j.trsl.2010.11.001. Epub 2010 Dec 5.