Improved stem cell-derived motoneuron survival, migration, sprouting, and innervation with enhanced expression of polysialic acid Journal Article

  

Authors:	El-Maarouf, A. ; Moyo-Lee-Yaw, D.; Rutishauser, U.
Article Title:	Improved stem cell-derived motoneuron survival, migration, sprouting, and innervation with enhanced expression of polysialic acid
Abstract:	Motoneurons (MNs) derived from mouse embryonic stem cells (ESCs) begin to express low levels of polysialic acid (PSA) at the time when they acquire an ability to migrate and extend neurites. PSA is known to promote cell migration and process outgrowth/guidance in the developing nervous system. To test if experimentally enhanced expression of PSA would augment these cellular events, the PSA-synthesizing polysialyltransferase was introduced into ESCs. In culture, the resulting higher PSA expression specifically increased neurite outgrowth and cell migration from differentiated embryoid bodies. In addition, the MN population obtained after sorting for HB9::GFP expression showed enhanced survival as well as extensive neurite outgrowth. Following transplantation of ESC-derived MNs into an adult sciatic nerve devoid of endogenous axons, the PSA augmentation increased the numbers of axons growing toward the denervated muscles. Migration of some transplanted cells inside the nerve toward muscle was also enhanced. Moreover, higher PSA expression selectively affected target innervation. It produced greater numbers of neuromuscular junctions in a predominantly fast twitch muscle and had no effect in a slow twitch muscle. These findings suggest that engineering of PSA expression in ESC could serve as an enhancement for MN cell therapy. © 2015 Cognizant Comm. Corp.
Keywords:	adult; controlled study; protein expression; unclassified drug; nonhuman; animal cell; mouse; cell survival; gene expression; embryo; embryonic stem cell; green fluorescent protein; animal experiment; in vivo study; neural stem cell; cell differentiation; in vitro study; cell population; transplantation; protein synthesis; nerve fiber; motor neurons; polysialic acid; western blotting; sialyltransferase; cell migration; stem cells; upregulation; schwann cell; nerve cell differentiation; nerve cell culture; innervation; fluorescence activated cell sorting; motoneuron; coculture; sciatic nerve; neural stem cell transplantation; neuromuscular synapse; nerve ending; nerve fiber growth; nerve sprouting; embryoid body; cell engineering; neurite; polysialylation; polysialyltransferase; male; priority journal; article; fast muscle; muscle denervation; stem cell culture
Journal Title:	Cell Transplantation
Volume:	24
Issue:	5
ISSN:	0963-6897
Publisher:	Cognizant Communication Corporation
Date Published:	2015-01-01
Start Page:	797
End Page:	809
Language:	English
DOI:	10.3727/096368914x679228
PROVIDER:	scopus
PUBMED:	24593882
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84928945795&partnerID=40&md5=f3dd9fd2b4b7d015a23e3a8aadce1bb0
Notes:	Export Date: 3 June 2015 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/74169