Sunday, April 08, 2012

ApoTransferrin and the fate of Neural Stem Cell/Progenitors

Implications for De-Myelinating Diseases Like MS and ALS

Dr. Juana María Pasquini and her team at the University of Buenos Aires are ongoing users of our Neural Stem Cell-Progenitor (NSC-NP) Markers. In this study, they use these markers to determine the states and fates of NSCs and NPs as they proliferate and differentiate and the related role of ApoTransferrin (aTF). Here we learn aTf exposure during differentiating conditions favours OL maturation from OPCs by promoting OL morphological development. This evidence supports a key role of Tf on the generation of OL from NSC/NPCs and highlights its potential in demyelinating disorder treatment: Silvestroff L , Franco PG , Pasquini JM (2012) ApoTransferrin: Dual Role on Adult Subventricular Zone-Derived Neurospheres. PLoS ONE 7(3): e33937. doi:10.1371/journal.pone.0033937.

Proliferation rates under different conditions are shown in A–C. BrdU incorporation (red) during proliferation (CTLP, A) or differentiation (CTLPCTLD, B). BrdU+ cells are expressed as a percentage of total nuclei for either condition in C. Free floating NS during proliferation express Nestin (D, green) and GFAP (E, green). After dissociation, NS-derived cells continue to express Nestin (F, green). PDGFRα+ (G, green) and NG2+ cells (H, green). Few MBP+ (I, green) cells were found under proliferative conditions. A large proportion of BrdU incorporating cells (J, red) co-expressed with NG2 (J, green). Some BLBP+ cells (K, green) incorporated BrdU (K, red). After differentiation (L–O), MBP+ cells were found with a highly branched and complex morphology (L, green). Cells expressed GFAP (M, green), as well as the neuronal NF200 marker (N, green). BrdU incorporating (O, red) cells were mostly NG2+ (O, green) during differentiation conditions. BrdU+ cells co-expressing NG2, as a proportion of total BrdU+ cells, are shown in P for either culture condition. A representative Western Blot membrane in Q shows how MBP levels increase in whole cell protein extracts as cells differentiate. The densitometric analysis of the MBP isoforms/GAPDH ratio of 5 independent experiments was semi-quantitated in R. All 4 MBP isoforms were pooled and considered as a single value before normalizing to GAPDH values. Blue colour in images indicates Höechst nuclear dye. Scale bar in A represents 250 µm for A and B. Scale bar in D equals 100 µm in D–I and L–N, scale bar in J equals 250 µm in J and O, and scale bar in K represents 50 µm. Bars in P represent mean values of 2 independent experiments. Bars in C and R represent Mean + SD of 4 and 5 individual cultures, respectively. Student's t Test was used to analyze data in C, while a One Way ANOVA with an SNK Post-test was used to analyze data in R. * p<0.05, ** p<0.01, *** p<0.001

Note:  PDGFRα+ is a marker for oligodendrocytes (OLs).

Here's the pathway model that sumarizes authors' findings
I will keep you posted on research that could implications for the discovery of de-myelinating disorder therapies.

2 comments:

Stem Cell Therapy said...

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. Healthy adult brains contain neural stem cells which divide to maintain general stem cell numbers, or become progenitor cells. In healthy adult animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). Interestingly, in pregnancy and after injury, this system appears to be regulated by growth factors and can increase the rate at which new brain matter is formedStem Cell Treatments

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