Progress in Mimicking Brain Microenvironments to Understand and Treat Neurological Disorders

Overview

Journal APL Bioeng

Date 2021 Apr 19

PMID 33869984

Citations 8

Authors

Mai T Ngo

Brendan A C Harley

Affiliations

Soon will be listed here.

Abstract

Neurological disorders including traumatic brain injury, stroke, primary and metastatic brain tumors, and neurodegenerative diseases affect millions of people worldwide. Disease progression is accompanied by changes in the brain microenvironment, but how these shifts in biochemical, biophysical, and cellular properties contribute to repair outcomes or continued degeneration is largely unknown. Tissue engineering approaches can be used to develop models to understand how the brain microenvironment contributes to pathophysiological processes linked to neurological disorders and may also offer constructs that promote healing and regeneration . In this Perspective, we summarize features of the brain microenvironment in normal and pathophysiological states and highlight strategies to mimic this environment to model disease, investigate neural stem cell biology, and promote regenerative healing. We discuss current limitations and resulting opportunities to develop tissue engineering tools that more faithfully recapitulate the aspects of the brain microenvironment for both and applications.

Citing Articles

Differential Lipid Signatures of Lumbar and Cisternal Cerebrospinal Fluid.

Toft-Bertelsen T, Andreassen S, Norager N, Simonsen A, Hasselbalch S, Juhler M Biomolecules. 2024; 14(11).

PMID: 39595607 PMC: 11591603. DOI: 10.3390/biom14111431.

Challenges and Future Perspectives in Modeling Neurodegenerative Diseases Using Organ-on-a-Chip Technology.

Pramotton F, Spitz S, Kamm R Adv Sci (Weinh). 2024; 11(32):e2403892.

PMID: 38922799 PMC: 11348103. DOI: 10.1002/advs.202403892.

Leveraging Biomaterial Platforms to Study Aging-Related Neural and Muscular Degeneration.

Hidalgo-Alvarez V, Madl C Biomolecules. 2024; 14(1).

PMID: 38254669 PMC: 10813704. DOI: 10.3390/biom14010069.

Emerging Materials, Wearables, and Diagnostic Advancements in Therapeutic Treatment of Brain Diseases.

Ramasubramanian B, Reddy V, Chellappan V, Ramakrishna S Biosensors (Basel). 2022; 12(12).

PMID: 36551143 PMC: 9775999. DOI: 10.3390/bios12121176.

Biochemical Pathways of Cellular Mechanosensing/Mechanotransduction and Their Role in Neurodegenerative Diseases Pathogenesis.

Tortorella I, Argentati C, Emiliani C, Morena F, Martino S Cells. 2022; 11(19).

PMID: 36231055 PMC: 9563116. DOI: 10.3390/cells11193093.

References

Janes K . Cell-to-Cell Transcript Variability: Seeing Signal in the Noise. Cell. 2015; 163(7):1566-8. PMC: 4926623. DOI: 10.1016/j.cell.2015.12.010. View

Chambers S, Fasano C, Papapetrou E, Tomishima M, Sadelain M, Studer L . Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009; 27(3):275-80. PMC: 2756723. DOI: 10.1038/nbt.1529. View

Freimann F, Muller S, Streitberger K, Guo J, Rot S, Ghori A . MR elastography in a murine stroke model reveals correlation of macroscopic viscoelastic properties of the brain with neuronal density. NMR Biomed. 2013; 26(11):1534-9. DOI: 10.1002/nbm.2987. View

Zhang D, Pekkanen-Mattila M, Shahsavani M, Falk A, Teixeira A, Herland A . A 3D Alzheimer's disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons. Biomaterials. 2013; 35(5):1420-8. DOI: 10.1016/j.biomaterials.2013.11.028. View

Cook D, Nguyen C, Chun H, Llorente I, Chiu A, Machnicki M . Hydrogel-delivered brain-derived neurotrophic factor promotes tissue repair and recovery after stroke. J Cereb Blood Flow Metab. 2016; 37(3):1030-1045. PMC: 5363479. DOI: 10.1177/0271678X16649964. View

Tonge D, de Burgh H, Docherty R, Humphries M, Craig S, Pizzey J . Fibronectin supports neurite outgrowth and axonal regeneration of adult brain neurons in vitro. Brain Res. 2012; 1453:8-16. PMC: 3989037. DOI: 10.1016/j.brainres.2012.03.024. View

Pistollato F, Chen H, Schwartz P, Basso G, Panchision D . Oxygen tension controls the expansion of human CNS precursors and the generation of astrocytes and oligodendrocytes. Mol Cell Neurosci. 2007; 35(3):424-35. DOI: 10.1016/j.mcn.2007.04.003. View

Zhang Z, Freitas B, Qian H, Lux J, Acab A, Trujillo C . Layered hydrogels accelerate iPSC-derived neuronal maturation and reveal migration defects caused by MeCP2 dysfunction. Proc Natl Acad Sci U S A. 2016; 113(12):3185-90. PMC: 4812712. DOI: 10.1073/pnas.1521255113. View

Vanlandewijck M, He L, Mae M, Andrae J, Ando K, Del Gaudio F . A molecular atlas of cell types and zonation in the brain vasculature. Nature. 2018; 554(7693):475-480. DOI: 10.1038/nature25739. View

10.

Huang Y, Tejero R, Lee V, Brusco C, Hannah T, Bertucci T . Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics. Commun Biol. 2021; 4(1):145. PMC: 7846610. DOI: 10.1038/s42003-021-01667-4. View

11.

Matson J, Stupp S . Self-assembling peptide scaffolds for regenerative medicine. Chem Commun (Camb). 2011; 48(1):26-33. PMC: 3355058. DOI: 10.1039/c1cc15551b. View

12.

Householder K, Dharmaraj S, Sandberg D, Wechsler-Reya R, Sirianni R . Fate of nanoparticles in the central nervous system after intrathecal injection in healthy mice. Sci Rep. 2019; 9(1):12587. PMC: 6715675. DOI: 10.1038/s41598-019-49028-w. View

13.

Moshayedi P, Nih L, Llorente I, Berg A, Cinkornpumin J, Lowry W . Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain. Biomaterials. 2016; 105:145-155. PMC: 5003628. DOI: 10.1016/j.biomaterials.2016.07.028. View

14.

Liao H, Huang W, Schachner M, Guan Y, Guo J, Yan J . Beta 1 integrin-mediated effects of tenascin-R domains EGFL and FN6-8 on neural stem/progenitor cell proliferation and differentiation in vitro. J Biol Chem. 2008; 283(41):27927-27936. DOI: 10.1074/jbc.M804764200. View

15.

Kolesky D, Homan K, Skylar-Scott M, Lewis J . Three-dimensional bioprinting of thick vascularized tissues. Proc Natl Acad Sci U S A. 2016; 113(12):3179-84. PMC: 4812707. DOI: 10.1073/pnas.1521342113. View

16.

Jeon J, Bersini S, Whisler J, Chen M, Dubini G, Charest J . Generation of 3D functional microvascular networks with human mesenchymal stem cells in microfluidic systems. Integr Biol (Camb). 2014; 6(5):555-63. PMC: 4307755. DOI: 10.1039/c3ib40267c. View

17.

Xiao W, Zhang R, Sohrabi A, Ehsanipour A, Sun S, Liang J . Brain-Mimetic 3D Culture Platforms Allow Investigation of Cooperative Effects of Extracellular Matrix Features on Therapeutic Resistance in Glioblastoma. Cancer Res. 2017; 78(5):1358-1370. PMC: 5935550. DOI: 10.1158/0008-5472.CAN-17-2429. View

18.

Herland A, van der Meer A, FitzGerald E, Park T, Sleeboom J, Ingber D . Distinct Contributions of Astrocytes and Pericytes to Neuroinflammation Identified in a 3D Human Blood-Brain Barrier on a Chip. PLoS One. 2016; 11(3):e0150360. PMC: 4773137. DOI: 10.1371/journal.pone.0150360. View

19.

Ngo M, Harley B . Perivascular signals alter global gene expression profile of glioblastoma and response to temozolomide in a gelatin hydrogel. Biomaterials. 2018; 198:122-134. PMC: 6292767. DOI: 10.1016/j.biomaterials.2018.06.013. View

20.

Zhong J, Chan A, Morad L, Kornblum H, Fan G, Carmichael S . Hydrogel matrix to support stem cell survival after brain transplantation in stroke. Neurorehabil Neural Repair. 2010; 24(7):636-44. PMC: 4697440. DOI: 10.1177/1545968310361958. View