PMID- 25390472 OWN - NLM STAT- MEDLINE DCOM- 20160204 LR - 20181202 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 24 IP - 7 DP - 2015 Apr 1 TI - Mesenchymal stem cells support neuronal fiber growth in an organotypic brain slice co-culture model. PG - 824-35 LID - 10.1089/scd.2014.0262 [doi] AB - Mesenchymal stem cells (MSCs) have been identified as promising candidates for neuroregenerative cell therapies. However, the impact of different isolation procedures on the functional and regenerative characteristics of MSC populations has not been studied thoroughly. To quantify these differences, we directly compared classically isolated bulk bone marrow-derived MSCs (bulk BM-MSCs) to the subpopulation Sca-1(+)Lin(-)CD45(-)-derived MSCs(-) (SL45-MSCs), isolated by fluorescence-activated cell sorting from bulk BM-cell suspensions. Both populations were analyzed with respect to functional readouts, that are, frequency of fibroblast colony forming units (CFU-f), general morphology, and expression of stem cell markers. The SL45-MSC population is characterized by greater morphological homogeneity, higher CFU-f frequency, and significantly increased nestin expression compared with bulk BM-MSCs. We further quantified the potential of both cell populations to enhance neuronal fiber growth, using an ex vivo model of organotypic brain slice co-cultures of the mesocortical dopaminergic projection system. The MSC populations were cultivated underneath the slice co-cultures without direct contact using a transwell system. After cultivation, the fiber density in the border region between the two brain slices was quantified. While both populations significantly enhanced fiber outgrowth as compared with controls, purified SL45-MSCs stimulated fiber growth to a larger degree. Subsequently, we analyzed the expression of different growth factors in both cell populations. The results show a significantly higher expression of brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor in the SL45-MSCs population. Altogether, we conclude that MSC preparations enriched for primary MSCs promote neuronal regeneration and axonal regrowth, more effectively than bulk BM-MSCs, an effect that may be mediated by a higher BDNF secretion. FAU - Sygnecka, Katja AU - Sygnecka K AD - 1 Translational Centre for Regenerative Medicine (TRM), University of Leipzig , Leipzig, Germany . FAU - Heider, Andreas AU - Heider A FAU - Scherf, Nico AU - Scherf N FAU - Alt, Rudiger AU - Alt R FAU - Franke, Heike AU - Franke H FAU - Heine, Claudia AU - Heine C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141217 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Culture Media, Conditioned) RN - 0 (Nestin) SB - IM MH - Animals MH - Brain/*cytology/drug effects MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Coculture Techniques MH - Culture Media, Conditioned/*pharmacology MH - Mesenchymal Stem Cells/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Nerve Fibers/*drug effects/metabolism/physiology MH - *Nerve Regeneration MH - Nestin/genetics/metabolism EDAT- 2014/11/13 06:00 MHDA- 2016/02/05 06:00 CRDT- 2014/11/13 06:00 PHST- 2014/11/13 06:00 [entrez] PHST- 2014/11/13 06:00 [pubmed] PHST- 2016/02/05 06:00 [medline] AID - 10.1089/scd.2014.0262 [doi] PST - ppublish SO - Stem Cells Dev. 2015 Apr 1;24(7):824-35. doi: 10.1089/scd.2014.0262. Epub 2014 Dec 17.