Polarized macrophages have distinct roles in the differentiation and migration of embryonic spinal-cord-derived neural stem cells after grafting to injured sites of spinal cord

Zhang, Kun, Zheng, Jingjing, Bian, Ganlan, Liu, Ling, Xue, Qian, Liu, Fangfang, Yu, Caiyong, Zhang, Haifeng, Song, Bing

, Chung, Sookja K, Ju, Gong and Wang, Jian 2015. Polarized macrophages have distinct roles in the differentiation and migration of embryonic spinal-cord-derived neural stem cells after grafting to injured sites of spinal cord. Molecular Therapy 23 (6) , pp. 1077-1091. 10.1038/mt.2015.46

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Official URL: http://dx.doi.org/10.1038/mt.2015.46

Abstract

Spinal cord injury (SCI) frequently provokes serious detrimental outcomes because neuronal regeneration is limited in the central nervous system (CNS). Thus, the creation of a permissive environment for transplantation therapy with neural stem/progenitor cells (NS/PCs) is a promising strategy to replace lost neuronal cells, promote repair, and stimulate functional plasticity after SCI. Macrophages are important SCI-associated inflammatory cells and a major source of secreted factors that modify the lesion milieu. Here, we used conditional medium (CM) from bone marrow-derived M1 or M2 polarized macrophages to culture murine NS/PCs. The NS/PCs showed enhanced astrocytic versus neuronal/oligodendrocytic differentiation in the presence of M1- versus M2-CM. Similarly, cotransplantation of NS/PCs with M1 and M2 macrophages into intact or injured murine spinal cord increased the number of engrafted NS/PC-derived astrocytes and neurons/oligodendrocytes, respectively. Furthermore, when cotransplantated with M2 macrophages, the NS/PC-derived neurons integrated into the local circuitry and enhanced locomotor recovery following SCI. Interesting, engrafted M1 macrophages promoted long-distance rostral migration of NS/PC-derived cells in a chemokine (C-X-C motif) receptor 4 (CXCR4)-dependent manner, while engrafted M2 macrophages resulted in limited cell migration of NS/PC-derived cells. Altogether, these findings suggest that the cotransplantation of NS/PCs together with polarized macrophages could constitute a promising therapeutic approach for SCI repair.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Dentistry
Publisher:	Elsevier (Cell Press)
ISSN:	1525-0016
Date of First Compliant Deposit:	23 October 2018
Date of Acceptance:	4 March 2015
Last Modified:	11 Oct 2023 22:12
URI:	https://orca.cardiff.ac.uk/id/eprint/116064