title: 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.
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.
authors: Department of Neurobiology, The Fourth Military Medical University, Xi'an, China.
authors: Kun
authors: K
authors: Zhang
authors: Department of Neurobiology, The Fourth Military Medical University, Xi'an, China.
authors: Jingjing
authors: J
authors: Zheng
authors: Department of Neurobiology, The Fourth Military Medical University, Xi'an, China.
authors: Ganlan
authors: G
authors: Bian
authors: Department of Neurobiology, The Fourth Military Medical University, Xi'an, China.
authors: Ling
authors: L
authors: Liu
authors: Department of Neurobiology, The Fourth Military Medical University, Xi'an, China.
authors: Qian
authors: Q
authors: Xue
authors: Department of Neurobiology, The Fourth Military Medical University, Xi'an, China.
authors: Fangfang
authors: F
authors: Liu
authors: Department of Neurobiology, The Fourth Military Medical University, Xi'an, China.
authors: Caiyong
authors: C
authors: Yu
authors: Department of Neurobiology, The Fourth Military Medical University, Xi'an, China.
authors: Haifeng
authors: H
authors: Zhang
authors: Cardiff Institute of Tissue Engineering & Repair, School of Dentistry, Cardiff University, Cardiff, UK.
authors: Bing
authors: B
authors: Song
authors: Department of Anatomy, The University of Hong Kong, HKSAR, Hong Kong, China.
authors: Sookja K
authors: SK
authors: Chung
authors: Department of Neurobiology, The Fourth Military Medical University, Xi'an, China. Electronic address: jugong@fmmu.edu.cn.
authors: Gong
authors: G
authors: Ju
authors: Department of Neurobiology, The Fourth Military Medical University, Xi'an, China. Electronic address: jwangfm@fmmu.edu.cn.
authors: Jian
authors: J
authors: Wang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D002490:Central Nervous System / Q000473:pathology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000637:transplantation*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000637:transplantation*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D016377:Organ Transplantation / Q000379:methods; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology*; D013119:Spinal Cord Injuries / Q000628:therapy
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4