title: Interplay between human microglia and neural stem/progenitor cells in an allogeneic co-culture model.
abstract: Experimental neural cell therapies, including donor neural stem/progenitor cells (NPCs) have been reported to offer beneficial effects on the recovery after an injury and to counteract inflammatory and degenerative processes in the central nervous system (CNS). The interplay between donor neural cells and the host CNS still to a large degree remains unclear, in particular in human allogeneic conditions. Here, we focused our studies on the interaction of human NPCs and microglia utilizing a co-culture model. In co-cultures, both NPCs and microglia showed increased survival and proliferation compared with mono-cultures. In the presence of microglia, a larger subpopulation of NPCs expressed the progenitor cell marker nestin, whereas a smaller group of NPCs expressed the neural markers polysialylated neural cell adhesion molecule, A2B5 and glial fibrillary acidic protein compared with NPC mono-cultures. Microglia thus hindered differentiation of NPCs. The presence of human NPCs increased microglial phagocytosis of latex beads. Furthermore, we observed that the expression of CD200 molecules on NPCs and the CD200 receptor protein on microglia was enhanced in co-cultures, whereas the release of transforming growth factor-β was increased suggesting anti-inflammatory features of the co-cultures. To conclude, the interplay between human allogeneic NPCs and microglia, significantly affected their respective proliferation and phenotype. Neural cell therapy including human donor NPCs may in addition to offering cell replacement, modulate host microglial phenotypes and functions to benefit neuroprotection and repair.
authors.affiliation: Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Geriatric Clinic Res Lab, Stockholm, Sweden; Department of Neurology, First Hospital of Jilin University, Changchun, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Erik
authors.initials: E
authors.lastname: Hjorth
authors.forename: Mingqin
authors.initials: M
authors.lastname: Zhu
authors.forename: Cinzia
authors.initials: C
authors.lastname: Calzarossa
authors.forename: Eva-Britt
authors.initials: EB
authors.lastname: Samuelsson
authors.forename: Marianne
authors.initials: M
authors.lastname: Schultzberg
authors.forename: Elisabet
authors.initials: E
authors.lastname: Åkesson
mesh_terms: D064591:Allografts; D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D017628:Microglia / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D064446:Orexin Receptors; D010587:Phagocytosis; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D044968:Regenerative Medicine; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; C477337:CD200R1 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; D053773:Transforming Growth Factor beta1; C042739:antigens, CD200
keywords: CD200; M1/M2 phenotype; human neural stem/progenitor cells; immunomodulation; microglia; phagocytosis; transforming growth factor-β
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