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Neuroectodermally converted human mesenchymal stromal cells provide cytoprotective effects on neural stem cells and inhibit their glial differentiation.

Abstract：

BACKGROUND AIMS:In recent years, bone marrow (BM)-derived mesenchymal stromal cells (MSC) have become a promising source for neuroregenerative therapies. We evaluated the trophic effects of neuroectodermally converted MSC (mNSC) on neural stem cells (NSC). METHODS:We quantified the expression of growth factors by mNSC using real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) and studied the effects of mNSC conditioned medium and mNSC (in direct co-culture) on NSC proliferation, differentiation and survival. RESULTS:Neuroectodermal conversion of human MSC induced high expression of growth factors at both mRNA and protein levels, most prominently hepatocyte growth factor, vascular endothelial growth factor and amphiregulin (37 +/- 17, 92 +/- 44 and 12 +/- 11 ng/10(5) cells, respectively), which remained at high levels upon co-culturing with neural cells. Accordingly, mNSC conditioned medium and co-cultivation with mNSC reduced cell death of NSC (36% of control), stimulated their proliferation, attenuated glial differentiation of NSC (7 +/- 3 versus 59 +/- 6%; P < 0.01) and protected NSC against the neurotoxin 6-hydroxydopamine (with half-maximally concentrations EC(50) values of 217 +/- 207 microM in the presence of mNSC compared with 62 +/- 49 microM for NSC alone). CONCLUSIONS:mNSC promote survival and proliferation, and inhibit glial differentiation, of NSC. Protection of NSC by mNSC against 6-hydroxy-dopamine is probably mediated by the release of cytotrophic factors. Our results promote neuroectodermally converted MSC as promising candidate cells for the development of neuroregenerative and neuroprotective therapies.

journal_name

Cytotherapy

journal_title

Cytotherapy

authors

Habisch HJ,Liebau S,Lenk T,Ludolph AC,Brenner R,Storch A

doi

10.3109/14653241003649502

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

491-504

issue

4

eissn

1465-3249

issn

1477-2566

pii

S1465-3249(10)70412-6

journal_volume

12

pub_type

杂志文章

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