PMID- 21696238
OWN - NLM
STAT- MEDLINE
DCOM- 20111207
LR  - 20181201
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Linking)
VI  - 13
IP  - 8
DP  - 2011 Sep
TI  - Neuronal plasticity of human Wharton's jelly mesenchymal stromal cells to the 
      dopaminergic cell type compared with human bone marrow mesenchymal stromal cells.
PG  - 918-32
LID - 10.3109/14653249.2011.579957 [doi]
AB  - BACKGROUND AIMS: Mesenchymal stromal cells (MSC) derived from Wharton's jelly 
      (WJ) of the umbilical cord are increasingly gaining prominence as substitutes for 
      bone marrow (BM) MSC. While MSC isolated from different tissue sources may share 
      common mesenchymal properties, the difference in their plasticity to individual 
      lineages is ill-defined. Thus the focus of this study was to estimate the 
      neuronal plasticity of WJ MSC to the dopaminergic (DA) cell type in comparison 
      with BM MSC. METHODS: For neuronal differentiation, MSC were exposed to 
      developmentally relevant cues for midbrain DA neurons: sonic hedgehog (SHH) and 
      fibroblast growth factor 8 (FGF8), along with basic fibroblast growth factor 
      (bFGF). RESULTS: Naive MSC from both sources constitutively expressed neuronal 
      markers. Flow cytometry data revealed that the control WJ MSC shared a signature 
      similar to BM MSC for early neuronal markers (nestin, musashi12 and A2B5) and 
      DA-specific markers [tyrosine hydroxylase (TH) and Nuclear Receptor related 
      protein 1 (Nurr1) but differed for mature neuronal proteins [beta-tubulin III and 
      microtubule-associated protein 2 (Map2ab)]. Similar populations of cells in both 
      sources of MSC were positive for the SHH receptors [patched (PTCH) and smoothened 
      (SMO)]. In induced BM and WJ MSC, real-time reverse transcriptase (RT)-polymerase 
      chain reaction (PCR) analysis showed similar levels of DA-related transcription 
      factors Nurr1 and Engrailed (En) 1. Immunocytochemical and flow cytometry 
      analysis showed an increase in mature neuronal marker Map2ab. Kv4.2, a K(+) 
      channel marker, was observed only in the induced MSC. Induced MSC also expressed 
      several DA-specific markers, TH, dopamine and cyclic AMP regulated phosphoprotein 
      (DARPP) 32, paired-like homeodomain transcription factor (PitX) 3 and vesicular 
      monoamine transporter (VMAT) 2, in comparable levels between the two sources. The 
      efficiency (c. 65%) of transdifferentiation of WJ MSC to TH-positive cells was 
      similar to that of induced BM MSC. Constitutive and inducible release of dopamine 
      was found to be similar between induced BM and WJ MSC, as measured by dopamine 
      enzyme-linked immunosorbent assay (ELISA). Interestingly, an adenosine 
      triphosphate (ATP)-stimulated change in intracellular Ca(2+) was observed in both 
      control and induced MSC, but only the induced MSC was capable of releasing 
      dopamine. CONCLUSIONS: Our data demonstrate that MSC from the two different 
      sources respond similarly to inductive cues to differentiate terminally to a DA 
      cell type, and the neuronal plasticity of human WJ MSC is comparable with that of 
      BM MSC.
FAU - Datta, Indrani
AU  - Datta I
AD  - Manipal Institute of Regenerative Medicine, Constituent Institute of Manipal 
      University, Bangalore, Karnataka, India. indrani.datta@manipal.edu
FAU - Mishra, Swati
AU  - Mishra S
FAU - Mohanty, Lipsa
AU  - Mohanty L
FAU - Pulikkot, Sunitha
AU  - Pulikkot S
FAU - Joshi, Preeti G
AU  - Joshi PG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110622
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
RN  - 0 (Biomarkers)
RN  - 0 (Hedgehog Proteins)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 148997-75-5 (Fibroblast Growth Factor 8)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Biomarkers/metabolism
MH  - Bone Marrow Cells/cytology
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Dopamine/metabolism
MH  - Dopaminergic Neurons/cytology/*metabolism
MH  - Fibroblast Growth Factor 2
MH  - Fibroblast Growth Factor 8
MH  - Hedgehog Proteins
MH  - Humans
MH  - Induced Pluripotent Stem Cells/cytology/*metabolism
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - *Neuronal Plasticity
MH  - *Stem Cell Niche
MH  - Wharton Jelly/cytology
EDAT- 2011/06/24 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/06/24 06:00
PHST- 2011/06/24 06:00 [entrez]
PHST- 2011/06/24 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - S1465-3249(11)70573-4 [pii]
AID - 10.3109/14653249.2011.579957 [doi]
PST - ppublish
SO  - Cytotherapy. 2011 Sep;13(8):918-32. doi: 10.3109/14653249.2011.579957. Epub 2011 
      Jun 22.