Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.

During retina development, retinal progenitor cell (RPC) proliferation and differentiation are regulated by complex inter- and intracellular interactions. Bone marrow mesenchymal stem cells (BMSCs) are reported to express a variety of cytokines and neurotrophic factors, which have powerful trophic a...

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Main Authors: Jing Xia, Min Luo, Ni Ni, Junzhao Chen, Yamin Hu, Yuan Deng, Jing Ji, Jibo Zhou, Xianqun Fan, Ping Gu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3786983?pdf=render
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author Jing Xia
Min Luo
Ni Ni
Junzhao Chen
Yamin Hu
Yuan Deng
Jing Ji
Jibo Zhou
Xianqun Fan
Ping Gu
author_facet Jing Xia
Min Luo
Ni Ni
Junzhao Chen
Yamin Hu
Yuan Deng
Jing Ji
Jibo Zhou
Xianqun Fan
Ping Gu
author_sort Jing Xia
collection DOAJ
description During retina development, retinal progenitor cell (RPC) proliferation and differentiation are regulated by complex inter- and intracellular interactions. Bone marrow mesenchymal stem cells (BMSCs) are reported to express a variety of cytokines and neurotrophic factors, which have powerful trophic and protective functions for neural tissue-derived cells. Here, we show that the expanded RPC cultures treated with BMSC-derived conditioned medium (CM) which was substantially enriched for bFGF and CNTF, expressed clearly increased levels of nuclear receptor TLX, an essential regulator of neural stem cell (NSC) self-renewal, as well as betacellulin (BTC), an EGF-like protein described as supporting NSC expansion. The BMSC CM- or bFGF-treated RPCs also displayed an obviously enhanced proliferation capability, while BMSC CM-derived bFGF knocked down by anti-bFGF, the effect of BMSC CM on enhancing RPC proliferation was partly reversed. Under differentiation conditions, treatment with BMSC CM or CNTF markedly favoured RPC differentiation towards retinal neurons, including Brn3a-positive retinal ganglion cells (RGCs) and rhodopsin-positive photoreceptors, and clearly diminished retinal glial cell differentiation. These findings demonstrate that BMSCs supported RPC proliferation and neuronal differentiation which may be partly mediated by BMSC CM-derived bFGF and CNTF, reveal potential limitations of RPC culture systems, and suggest a means for optimizing RPC cell fate determination in vitro.
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spelling doaj.art-51868ca1a60546fea4dc30dc1d01d2372022-12-21T19:17:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7615710.1371/journal.pone.0076157Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.Jing XiaMin LuoNi NiJunzhao ChenYamin HuYuan DengJing JiJibo ZhouXianqun FanPing GuDuring retina development, retinal progenitor cell (RPC) proliferation and differentiation are regulated by complex inter- and intracellular interactions. Bone marrow mesenchymal stem cells (BMSCs) are reported to express a variety of cytokines and neurotrophic factors, which have powerful trophic and protective functions for neural tissue-derived cells. Here, we show that the expanded RPC cultures treated with BMSC-derived conditioned medium (CM) which was substantially enriched for bFGF and CNTF, expressed clearly increased levels of nuclear receptor TLX, an essential regulator of neural stem cell (NSC) self-renewal, as well as betacellulin (BTC), an EGF-like protein described as supporting NSC expansion. The BMSC CM- or bFGF-treated RPCs also displayed an obviously enhanced proliferation capability, while BMSC CM-derived bFGF knocked down by anti-bFGF, the effect of BMSC CM on enhancing RPC proliferation was partly reversed. Under differentiation conditions, treatment with BMSC CM or CNTF markedly favoured RPC differentiation towards retinal neurons, including Brn3a-positive retinal ganglion cells (RGCs) and rhodopsin-positive photoreceptors, and clearly diminished retinal glial cell differentiation. These findings demonstrate that BMSCs supported RPC proliferation and neuronal differentiation which may be partly mediated by BMSC CM-derived bFGF and CNTF, reveal potential limitations of RPC culture systems, and suggest a means for optimizing RPC cell fate determination in vitro.http://europepmc.org/articles/PMC3786983?pdf=render
spellingShingle Jing Xia
Min Luo
Ni Ni
Junzhao Chen
Yamin Hu
Yuan Deng
Jing Ji
Jibo Zhou
Xianqun Fan
Ping Gu
Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.
PLoS ONE
title Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.
title_full Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.
title_fullStr Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.
title_full_unstemmed Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.
title_short Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.
title_sort bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells
url http://europepmc.org/articles/PMC3786983?pdf=render
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