Current Methods for the Isolation and Cultivation of Microglia (Review)
The role and morphological features of microglia (M1 and M2 microglia, “stellate”, “amoeboid”, giant, round-shaped, rod-shaped, dysfunctional, etc.) in vivo under physiological conditions and during the development of neurodegenerative diseases have been described. Various methods and techniques of microglia isolation from adult (density gradient isolation, use of “magnetic beads”, from mesenchymal bone marrow progenitor cells) and newborn (obtaining from a mixed glial culture, density gradient isolation) animals have been considered, including microglia isolation from the cerebral cortex or hippocampus. Various methods of cell cultivation have been shown, including obtaining two-dimensional and three-dimensional cell cultures (on scaffolds, hydrogels, nanofibers), co-cultures on slice cultures of the hippocampus, as well as changes in microglia during cultivation.
- Hickman S., Izzy S., Sen P., Morsett L., El Khoury J. Microglia in neurodegeneration. Nat Neurosci 2018; 21(10): 1359–1369, https://doi.org/10.1038/s41593-018-0242-x.
- Río Hortega P. Noticia de un nuevo y fácil método para la coloración de la neuroglia y el tejido conjuntivo. Trab Lab Invest Biol 1918; 15: 367–378.
- Wolf S.A., Boddeke H.W.G.M., Kettenmann H. Microglia in physiology and disease. Annu Rev Physiol 2017; 79: 619–643, https://doi.org/10.1146/annurev-physiol-022516-034406.
- Lawson L.J., Perry V.H., Dri P., Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 1990; 39: 151–170.
- Hamby M.E., Sofroniew M.V. Reactive astrocytes as therapeutic targets for CNS disorders. Neurotherapeutics 2010; 7(4): 494–506, https://doi.org/10.1016/j.nurt.2010.07.003.
- Garden G.A., Möller T.J. Microglia biology in health and disease. J Neuroimmune Pharmacol 2006; 1(2): 127–137, https://doi.org/10.1007/s11481-006-9015-5.
- Rock R.B., Gekker G., Hu S., Sheng W.S., Cheeran M., Lokensgard J.R., Peterson P.K. Role of microglia in central nervous system infections. Clin Microbiol Rev 2004; 17(4): 942–964, https://doi.org/10.1128/cmr.17.4.942-964.2004.
- Subramaniam S.R., Federoff H.J. Targeting microglial activation states as a therapeutic avenue in Parkinson’s disease. Front Aging Neurosci 2017; 9: 176, https://doi.org/10.3389/fnagi.2017.00176.
- Fu R., Shen Q., Xu P., Luo J.J., Tang Y. Phagocytosis of microglia in the central nervous system diseases. Mol Neurobiol 2014; 49(3): 1422–1434, https://doi.org/10.1007/s12035-013-8620-6.
- Tang Z., Gan Y., Lui Q., Yin J.X., Liu Q., Shi J., Shi F.D. CX3CR1 deficiency suppresses activation and neurotoxicity of microglia/macrophage in experimental ischemic stroke. J Neuroinflammation 2014; 11: 26, https://doi.org/10.1186/1742-2094-11-26.
- Beins E., Ulas T., Ternes S., Neumann H., Schultze J.L., Zimmer A. Characterization of inflammatory markers and transcriptome profiles of differentially activated embryonic stem cell-derived microglia. Glia 2016; 64(6): 1007–1020, https://doi.org/10.1002/glia.22979.
- Ghazanfari R., Zacharaki D., Li H., Ching Lim H., Soneji S., Scheding S. Human primary bone marrow mesenchymal stromal cells and their in vitro progenies display distinct transcriptional profile signatures. Sci Rep 2017; 7(1): 10338, https://doi.org/10.1038/s41598-017-09449-x.
- Muffat J., Li Y., Yuan B., Mitalipova M., Omer A., Corcoran S., Bakiasi G., Tsai L.H., Aubourg P., Ransohoff R.M., Jaenisch R. Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat Med 2016; 22(11): 1358–1367, https://doi.org/10.1038/nm.4189.
- Hanisch U.K. Functional diversity of microglia — how heterogeneous are they to begin with? Front Cell Neurosci 2013; 7: 65, https://doi.org/10.3389/fncel.2013.00065.
- Taylor R.A., Sansing L.H. Microglial responses after ischemic stroke and intracerebral hemorrhage. Clin Dev Immunol 2013; 2013: 746068, https://doi.org/10.1155/2013/746068.
- Luo C., Jian C., Liao Y., Huang Q., Wu Y., Liu X., Zou D., Wu Y. The role of microglia in multiple sclerosis. Neuropsychiatr Dis Treat 2017; 13: 1661–1667, https://doi.org/10.2147/ndt.s140634.
- Luo X.G., Chen S.D. The changing phenotype of microglia from homeostasis to disease. Transl Neurodegener 2012; 1(1): 9, https://doi.org/10.1186/2047-9158-1-9.
- Jones A., Kulozik P., Ostertag A., Herzig S. Common pathological processes and transcriptional pathways in Alzheimer’s disease and type 2 diabetes. J Alzheimers Dis 2009; 16(4): 787–808, https://doi.org/10.3233/jad-2009-0973.
- Shen Y., Sun A., Wang Y., Cha D., Wang H., Wang F., Feng L., Fang S., Shen Y. Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation. J Neuroinflammation 2012; 9: 254, https://doi.org/10.1186/1742-2094-9-254.
- Adeluyi A., Guerin L., Fisher M.L., Galloway A., Cole R.D., Chan S.S.L., Wyatt M.D., Davis S.W., Freeman L.R., Ortinski P.I., Turner J.R. Microglia morphology and proinflammatory signaling in the nucleus accumbens during nicotine withdrawal. Sci Adv 2019; 5(10): eaax7031, https://doi.org/10.1126/sciadv.aax7031.
- Paasila P.J., Davies D.S., Kril J.J., Goldsbury C., Sutherland G.T. The relationship between the morphological subtypes of microglia and Alzheimer’s disease neuropathology. Brain Pathol 2019; 29(6): 726–740, https://doi.org/10.1111/bpa.12717.
- Tam W.Y., Au N.P., Ma C.H. The association between laminin and microglial morphology in vitro. Sci Rep 2016; 6: 28580, https://doi.org/10.1038/srep28580.
- Tam W.Y., Ma C.H. Bipolar/rod-shaped microglia are proliferating microglia with distinct M1/M2 phenotypes. Sci Rep 2014; 4: 7279, https://doi.org/10.1038/srep07279.
- Kolos E., Korzhevsky D. Spinal cord microglia in health and disease. Acta Naturae 2020; 12(1): 4–17, https://doi.org/10.32607/actanaturae.10934.
- Walker F.R., Beynon S.B., Jones K.A., Zhao Z., Kongsui R., Cairns M., Nilsson M. Dynamic structural remodelling of microglia in health and disease: a review of the models, the signals and the mechanisms. Brain Behav Immun 2014; 37: 1–14, https://doi.org/10.1016/j.bbi.2013.12.010.
- Holloway O.G., Canty A.J., King A.E., Ziebell J.M. Rod microglia and their role in neurological diseases. Semin Cell Dev Biol 2019; 94: 96–103, https://doi.org/10.1016/j.semcdb.2019.02.005.
- Paolicelli R.C., Bolasco G., Pagani F., Maggi L., Scianni M., Panzanelli P., Giustetto M., Ferreira T.A., Guiducci E., Dumas L., Ragozzino D., Gross C.T. Synaptic pruning by microglia is necessary for normal brain development. Science 2011; 333(6048): 1456‒1458, https://doi.org/10.1126/science.1202529.
- Parkhurst C.N., Yang G., Ninan I., Savas J.N., Yates J.R. III, Lafaille J.J., Hempstead B.L., Littman D.R., Gan W.B. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 2013; 155(7): 1596‒1609, https://doi.org/10.1016/j.cell.2013.11.030.
- Gogoleva V.S., Drutskaya M.S., Atretkhany K.S.N. The role of microglia in the homeostasis of the central nervous system and neuroinflammation. Molekularnaa biologia 2019; 53(5): 790‒798, https://doi.org/10.1134/s0026898419050057.
- Guruswamy R., ElAli A. Complex roles of microglial cells in ischemic stroke pathobiology: new insights and future directions. Int J Mol Sci 2017; 18(3): 496, https://doi.org/10.3390/ijms18030496.
- Tang Y., Li T., Li J., Yang J., Liu H., Zhang X.J., Le W. Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson’s disease. Cell Death Differ 2014; 21(3): 369–380, https://doi.org/10.1038/cdd.2013.159.
- Patel A.R., Ritzel R., McCullough L.D., Liu F. Microglia and ischemic stroke: a double-edged sword. Int J Physiol Pathophysiol Pharmacol 2013; 5(2): 73–90.
- Sanchez-Guajardo V., Barnum C.J., Tansey M.G., Romero-Ramos M. Neuroimmunological processes in Parkinson’s disease and their relation to α-synuclein: microglia as the referee between neuronal processes and peripheral immunity. ASN Neuro 2013; 5(2): 113–139, https://doi.org/10.1042/an20120066.
- Perego C., Fumagalli S., De Simoni M.G. Temporal pattern of expression and colocalization of microglia/macrophage phenotype markers following brain ischemic injury in mice. J Neuroinflammation 2011; 8: 174, https://doi.org/10.1186/1742-2094-8-174.
- Weitz T.M., Town T. Microglia in Alzheimer’s disease: it’s all about context. Int J Alzheimers Dis 2012; 2012: 314185, https://doi.org/10.1155/2012/314185.
- Doring A., Yong V.W. The good, the bad and the ugly. Macrophages/microglia with a focus on myelin repair. Front Biosci (Schol Ed) 2011; 3: 846–856, https://doi.org/10.2741/191.
- Tejera D., Heneka M.T. Microglia in Alzheimer’s disease: the good, the bad and the ugly. Curr Alzheimer Res 2016; 13(4): 370–380, https://doi.org/10.2174/1567205013666151116125012.
- Block M.L., Hong J.S. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 2005; 76(2): 77–98, https://doi.org/10.1155/2012/314185.
- Jin R., Yang G., Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 2010; 87(5): 779–789, https://doi.org/10.1189/jlb.1109766.
- Marks L., Carswell H.V., Peters E.E., Graham D.I., Patterson J., Dominiczak A.F., Macrae I.M. Characterization of the microglial response to cerebral ischemia in the stroke-prone spontaneously hypertensive rat. Hypertension 2001; 38(1): 116–122, https://doi.org/10.1161/01.hyp.38.1.116.
- Norden D.M., Muccigrosso M.M., Godbout J.P. Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease. Neuropharmacology 2015; 96(Pt A): 29–41, https://doi.org/10.1016/j.neuropharm.2014.10.028.
- Chang Y., Zhu J., Wang D., Li H., He Y., Liu K., Wang X., Peng Y., Pan S., Huang K. NLRP3 inflammasome-mediated microglial pyroptosis is critically involved in the development of post-cardiac arrest brain injury. J Neuroinflammation 2020; 17(1): 219, https://doi.org/10.1186/s12974-020-01879-1.
- Kuvacheva N.V., Morgun A.V., Hilazheva E.D., Malinovskaya N.A., Gorina Y.V., Pozhilenkova E.A., Frolova O.V., Trufanova L.V., Martynova G.P., Salmina A.B. Inflammasomes forming: new mechanisms of intercellular interactions regulation and secretory activity of the cells. Sibirskoe medicinskoe obozrenie 2013; 5: 3–10.
- Kabba J.A., Xu Y., Christian H., Ruan W., Chenai K., Xiang Y., Zhang L., Saavedra J.M., Pang T. Microglia: housekeeper of the central nervous system. Cell Mol Neurobiol 2018; 38(1): 53–71, https://doi.org/10.1007/s10571-017-0504-2.
- Tejera D., Heneka M.T. Microglia in neurodegenerative disorders. Methods Mol Biol 2019; 2034: 57–67, https://doi.org/10.1007/978-1-4939-9658-2_5.
- Ricci G., Volpi L., Pasquali L., Petrozzi L., Siciliano G. Astrocyte-neuron interactions in neurological disorders. J Biol Phys 2009; 35(4): 317–336, https://doi.org/10.1007/s10867-009-9157-9.
- Scuderi C., Stecca C., Iacomino A., Steardo L. Role of astrocytes in major neurological disorders: the evidence and implications. IUBMB Life 2013; 65(12): 957–961, https://doi.org/10.1002/iub.1223.
- Lucin K.M., O’Brien C.E., Bieri G., Czirr E., Mosher K.I., Abbey R.J., Mastroeni D.F., Rogers J., Spencer B., Masliah E., Wyss-Coray T. Microglial beclin 1 regulates retromer trafficking and phagocytosis and is impaired in Alzheimer’s disease. Neuron 2013; 79(5): 873–886, https://doi.org/10.1016/j.neuron.2013.06.046.
- Saijo K., Glass C.K. Microglial cell origin and phenotypes in health and disease. Nat Rev Immunol 2011; 11(11): 775–787, https://doi.org/10.1038/nri3086.
- Perry V.H., Holmes C. Microglial priming in neurodegenerative disease. Nat Rev Neurol 2014; 10(4): 217–224, https://doi.org/10.1038/nrneurol.2014.38.
- Wong W.T. Microglial aging in the healthy CNS: phenotypes, drivers, and rejuvenation. Front Cell Neurosci 2013; 7: 22, https://doi.org/10.3389/fncel.2013.00022.
- Mizee M.R., Miedema S.S., van der Poel M., Adelia, Schuurman K.G., van Strien M.E., Melief J., Smolders J., Hendrickx D.A., Heutinck K.M., Hamann J., Huitinga I. Isolation of primary microglia from the human post-mortem brain: effects of ante- and post-mortem variables. Acta Neuropathol Commun 2017; 5(1): 16, https://doi.org/10.1186/s40478-017-0418-8.
- Masuch A., Biber K. Replenishment of organotypic hippocampal slice cultures with neonatal or adult microglia. Methods Mol Biol 2019; 2034: 127–147, https://doi.org/10.1007/978-1-4939-9658-2_10.
- Zhuravleva M.N., Mukhamedshina Y.O., Arkhipova S.S., Sanatova E.R., Rizvanov A.A. The morphological and phenotypic characteristics of microglia at different stages of cultivation and transplantation in the area of spinal cord injury in rats. Geny i kletki 2015; 10(4): 34–39.
- Koss K.M., Churchward M.A., Jeffery A.F., Mushahwar V.K., Elias A.L., Todd K.G. Improved 3D hydrogel cultures of primary glial cells for in vitro modelling of neuroinflammation. J Vis Exp 2017; 130: 56615, https://doi.org/10.3791/56615.
- Frank M.G., Wieseler-Frank J.L., Watkins L.R., Maier S.F. Rapid isolation of highly enriched and quiescent microglia from adult rat hippocampus: immunophenotypic and functional characteristics. J Neurosci Methods 2006; 151(2): 121–130, https://doi.org/10.1016/j.jneumeth.2005.06.026.
- Lee J.K., Tansey M.G. Microglia isolation from adult mouse brain. Methods Mol Biol 2013; 1041: 17–23, https://doi.org/10.1007/978-1-62703-520-0_3.
- Hickman S.E., El Khoury J. Analysis of the microglial sensome. Methods Mol Biol 2019; 2034: 305–323, https://doi.org/10.1007/978-1-4939-9658-2_23.
- Grabert K., McColl B.W. Isolation and phenotyping of adult mouse microglial cells. Methods Mol Biol 2018; 1784: 77–86, https://doi.org/10.1007/978-1-4939-7837-3_7.
- Holt L.M., Stoyanof S.T., Olsen M.L. Magnetic cell sorting for in vivo and in vitro astrocyte, neuron, and microglia analysis. Curr Protoc Neurosci 2019; 88(1): e71, https://doi.org/10.1002/cpns.71.
- Timmerman R., Burm S.M., Bajramovic J.J. An overview of in vitro methods to study microglia. Front Cell Neurosci 2018; 12: 242, https://doi.org/10.3389/fncel.2018.00242.
- Appel J.R., Ye S., Tang F., Sun D., Zhang H., Mei L., Xiong W.C. Increased microglial activity, impaired adult hippocampal neurogenesis, and depressive-like behavior in microglial VPS35-depleted mice. J Neurosci 2018; 38(26): 5949–5968, https://doi.org/10.1523/jneurosci.3621-17.2018.
- Hinze A., Stolzing A. Microglia differentiation using a culture system for the expansion of mice non-adherent bone marrow stem cells. J Inflamm (Lond) 2012; 9(1): 12, https://doi.org/10.1186/1476-9255-9-12.
- Amend S.R., Valkenburg K.C., Pienta K.J. Murine hind limb long bone dissection and bone marrow isolation. J Vis Exp 2016; 110: 53936, https://doi.org/10.3791/53936.
- Tanti G.K., Srivastava R., Kalluri S.R., Nowak C., Hemmer B. Isolation, culture and functional characterization of glia and endothelial cells from adult pig brain. Front Cell Neurosci 2019; 13: 333, https://doi.org/10.3389/fncel.2019.00333.
- Stark J.C., Wallace E., Lim R., Leaw B. Characterization and isolation of mouse primary microglia by density gradient centrifugation. J Vis Exp 2018; 132: 57065, https://doi.org/10.3791/57065.
- Akhmetzyanova E.R., Mukhamedshina Y.O., Zhuravleva M.N., Galieva L.R., Kostennikov A.A., Garanina E.E., Rizvanov A.A. Transplantation of microglia in the area of spinal cord injury in an acute period increases tissue sparing, but not functional recovery. Front Cell Neurosci 2018; 12: 507, https://doi.org/10.3389/fncel.2018.00507.
- Gage G.J., Kipke D.R., Shain W. Whole animal perfusion fixation for rodents. J Vis Exp 2012; 65: 3564, https://doi.org/10.3791/3564.
- Cunningham C.L., Martínez-Cerdeño V., Noctor S.C. Microglia regulate the number of neural precursor cells in the developing cerebral cortex. J Neurosci 2013; 33(10): 4216–4233, https://doi.org/10.1523/jneurosci.3441-12.2013.
- Swamydas M., Lionakis M.S. Isolation, purification and labeling of mouse bone marrow neutrophils for functional studies and adoptive transfer experiments. J Vis Exp 2013; 77: e50586, https://doi.org/10.3791/50586.
- Zhang X., Goncalves R., Mosser D.M. The isolation and characterization of murine macrophages. Curr Protoc Immunol 2008; 83: 14.1, https://doi.org/10.1002/0471142735.im1401s83.
- Cizkova D., Devaux S., Le Marrec-Croq F., Franck J., Slovinska L., Blasko J., Rosocha J., Spakova T., Lefebvre C., Fournier I., Salzet M. Modulation properties of factors released by bone marrow stromal cells on activated microglia: an in vitro study. Sci Rep 2014; 4: 7514, https://doi.org/10.1038/srep07514.
- Wang F., Zhang S., Jeon R., Vuckovic I., Jiang X., Lerman A., Folmes C.D., Dzeja P.D., Herrmann J. Interferon gamma induces reversible metabolic reprogramming of M1 macrophages to sustain cell viability and pro-inflammatory activity. EBioMedicine 2018; 30: 303–316, https://doi.org/10.1016/j.ebiom.2018.02.009.
- Huynh H.K., Dorovini-Zis K. Effects of interferon-gamma on primary cultures of human brain microvessel endothelial cells. Am J Pathol 1993; 142(4): 1265–1278.
- Fixe P., Praloran V. M-CSF: haematopoietic growth factor or inflammatory cytokine? Cytokine 1998; 10(1): 32–37, https://doi.org/10.1006/cyto.1997.0249.
- Ushach I., Zlotnik A. Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage. J Leukoc Biol 2016; 100(3): 481–489, https://doi.org/10.1189/jlb.3ru0316-144r.
- Gottipamula S., Ashwin K.M., Muttigi M.S., Kannan S., Kolkundkar U., Seetharam R.N. Isolation, expansion and characterization of bone marrow-derived mesenchymal stromal cells in serum-free conditions. Cell Tissue Res 2014; 356(1): 123–135, https://doi.org/10.1007/s00441-013-1783-7.
- Gottipamula S., Muttigi M.S., Chaansa S., Ashwin K.M., Priya N., Kolkundkar U., Sundar Raj S., Majumdar A.S., Seetharam R.N. Large-scale expansion of pre-isolated bone marrow mesenchymal stromal cells in serum-free conditions. J Tissue Eng Regen Med 2016; 10(2): 108–119, https://doi.org/10.1002/term.1713.
- Sanchez-Ramos J., Song S., Cardozo-Pelaez F., Hazzi C., Stedeford T., Willing A., Freeman T.B., Saporta S., Janssen W., Patel N., Cooper D.R., Sanberg P.R. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 2000; 164(2): 247–256, https://doi.org/10.1006/exnr.2000.7389.
- Vogel D.Y., Glim J.E., Stavenuiter A.W., Breur M., Heijnen P., Amor S., Dijkstra C.D., Beelen R.H. Human macrophage polarization in vitro: maturation and activation methods compared. Immunobiology 2014; 219(9): 695–703, https://doi.org/10.1016/j.imbio.2014.05.002.
- Maridas D.E., Rendina-Ruedy E., Le P.T., Rosen C.J. Isolation, culture, and differentiation of bone marrow stromal cells and osteoclast progenitors from mice. J Vis Exp 2018; 131: 56750, https://doi.org/10.3791/56750.
- Servet-Delprat C., Arnaud S., Jurdic P., Nataf S., Grasset M.F., Soulas C., Domenget C., Destaing O., Rivollier A., Perret M., Dumontel C., Hanau D., Gilmore G.L., Belin M.F., Rabourdin-Combe C., Mouchiroud G. Flt3+ macrophage precursors commit sequentially to osteoclasts, dendritic cells and microglia. BMC Immunol 2002; 3: 15, https://doi.org/10.1186/1471-2172-3-15.
- Giulian D., Ingeman J.E. Colony-stimulating factors as promoters of ameboid microglia. J Neurosci 1988; 8(12): 4707–4717, https://doi.org/10.1523/jneurosci.08-12-04707.1988.
- Chhor V., Le Charpentier T., Lebon S., Oré M.V., Celador I.L., Josserand J., Degos V., Jacotot E., Hagberg H., Sävman K., Mallard C., Gressens P., Fleiss B. Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro. Brain Behav Immun 2013; 32: 70–85, https://doi.org/10.1016/j.bbi.2013.02.005.
- Jablonski K.A., Amici S.A., Webb L.M., Ruiz-Rosado Jde D., Popovich P.G., Partida-Sanchez S., Guerau-de-Arellano M. Novel markers to delineate murine M1 and M2 macrophages. PLoS One 2015; 10(12): e0145342, https://doi.org/10.1371/journal.pone.0145342.
- Galimova E.S., Galagudza М.М. Two-dimensional and three-dimensional cell culture models in vitro: pros and cons. Bulletenʹ sibirskoj mediciny 2018; 17(3): 188–196, https://doi.org/10.20538/1682-0363-2018-3-188-196.
- Watson P.M.D., Kavanagh E., Allenby G., Vassey M. Bioengineered 3D glial cell culture systems and applications for neurodegeneration and neuroinflammation. SLAS Discov 2017; 22(5): 583–601, https://doi.org/10.1177/2472555217691450.
- Zhu J. Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials 2010; 31(17): 4639–4656, https://doi.org/10.1016/j.biomaterials.2010.02.044.
- Alves M.H., Jensen B.E., Smith A.A., Zelikin A.N. Poly(vinyl alcohol) physical hydrogels: new vista on a long serving biomaterial. Macromol Biosci 2011; 11(10): 1293–1313, https://doi.org/10.1002/mabi.201100145.
- Andersen T., Auk-Emblem P., Dornish M. 3D cell culture in alginate hydrogels. Microarrays (Basel) 2015; 4(2): 133–161, https://doi.org/10.3390/microarrays4020133.
- Dash T.K., Konkimalla V.B. Polymeric modification and its implication in drug delivery: poly-ε-caprolactone (PCL) as a model polymer. Mol Pharm 2012; 9(9): 2365–2379, https://doi.org/10.1021/mp3001952.
- East E., Golding J.P., Phillips J.B. A versatile 3D culture model facilitates monitoring of astrocytes undergoing reactive gliosis. J Tissue Eng Regen Med 2009; 3(8): 634–646, https://doi.org/10.1002/term.209.
- Hawkins B.T., Grego S., Sellgren K.L. Three-dimensional culture conditions differentially affect astrocyte modulation of brain endothelial barrier function in response to transforming growth factor β1. Brain Res 2015; 1608: 167–176, https://doi.org/10.1016/j.brainres.2015.02.025.
- Sun Y., Li W., Wu X., Zhang N., Zhang Y., Ouyang S., Song X., Fang X., Seeram R., Xue W., He L., Wu W. Functional self-assembling peptide nanofiber hydrogels designed for nerve degeneration. ACS Appl Mater Interf 2016; 8(3): 2348–2359, https://doi.org/10.1021/acsami.5b11473.
- Rocha D.N., Ferraz-Nogueira J.P., Barrias C.C., Relvas J.B., Pêgo A.P. Extracellular environment contribution to astrogliosis: lessons learned from a tissue engineered 3D Model of the glial scar. Front Cell Neurosci 2015; 9: 377, https://doi.org/10.3389/fncel.2015.00377.
- Min S.K., Jung S.M., Ju J.H., Kwon Y.S., Yoon G.H., Shin H.S. Regulation of astrocyte activity via control over stiffness of cellulose acetate electrospun nanofiber. In Vitro Cell Devel Biol Anim 2015; 51(9): 933–940, https://doi.org/10.1007/s11626-015-9925-8.
- Tiryaki V.M., Ayres V.M., Khan A.A., Ahmed I., Shreiber D.I., Meiners S. Nanofibrillar scaffolds induce preferential activation of Rho GTPases in cerebral cortical astrocytes. Intl J Nanom 2012; 7: 3891–3905, https://doi.org/10.2147/ijn.s32681.
- Smith I., Haag M., Ugbode C., Tams D., Rattray M., Przyborski S., Bithell A., Whalley B.J. Neuronal-glial populations form functional networks in a biocompatible 3D scaffold. Neuroscience Lett 2015; 609: 198–202, https://doi.org/10.1016/j.neulet.2015.10.044.
- Ugbode C.I., Hirst W.D., Rattray M. Astrocytes grown in Alvetex® three dimensional scaffolds retain a non-reactive phenotype. Neurochem Res 2016; 41(8): 1857–1867, https://doi.org/10.1007/s11064-016-1911-3.
- Zhou K., Motamed S., Thouas G.A., Bernard C.C., Li D., Parkington H.C., Coleman H.A., Finkelstein D.I., Forsythe J.S. Graphene functionalized scaffolds reduce the inflammatory response and supports endogenous neuroblast migration when implanted in the adult brain. PloS One 2016; 11(3): e0151589, https://doi.org/10.1371/journal.pone.0151589.
- Crews F.T., Vetreno R.P. Mechanisms of neuroimmune gene induction in alcoholism. Psychopharmacology (Berl) 2016; 233(9): 1543–1557, https://doi.org/10.1007/s00213-015-3906-1.
- Fernández-Arjona M.D.M., Grondona J.M., Granados-Durán P., Fernández-Llebrez P., López-Ávalos M.D. Microglia morphological categorization in a rat model of neuroinflammation by hierarchical cluster and principal components analysis. Front Cell Neurosci 2017; 11: 235, https://doi.org/10.3389/fncel.2017.00235.
- Kettenmann H., Hanisch U.K., Noda M., Verkhratsky A. Physiology of microglia. Physiolog Rev 2011; 91(2): 461–553, https://doi.org/10.1152/physrev.00011.2010.
- Pöttler M., Zierler S., Kerschbaum H.H. An artificial three-dimensional matrix promotes ramification in the microglial cell-line, BV-2. Neurosci Lett 2006; 410(2): 137–140, https://doi.org/10.1016/j.neulet.2006.09.082.
- Song Q., Jiang Z., Li N., Liu P., Liu L., Tang M., Cheng G. Anti-inflammatory effects of three-dimensional graphene foams cultured with microglial cells. Biomaterials 2014; 35(25): 6930–6940, https://doi.org/10.1016/j.biomaterials.2014.05.002.
- Haw R.T., Tong C.K., Yew A., Lee H.C., Phillips J.B., Vidyadaran S. A three-dimensional collagen construct to model lipopolysaccharide-induced activation of BV2 microglia. J Neuroinflammation 2014; 11: 134, https://doi.org/10.1186/1742-2094-11-134.