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Current Stem Cell Reports

, Volume 5, Issue 3, pp 109–114 | Cite as

Engineered Biomimetic Neural Stem Cell Niche

  • Rita Matta
  • Anjelica L. GonzalezEmail author
Stem Cell Switches and Regulators (K Hirschi, Section Editor)
  • 41 Downloads
Part of the following topical collections:
  1. Topical Collection on Stem Cell Switches and Regulators

Abstract

Purpose of Review

Neural stem cells (NSCs) have the potential to proliferate and differentiate into functional neurons, heightening their potential use for therapeutic applications. This review explores bioengineered systems which recapitulate NSC niche cell-cell and cell-matrix interactions.

Recent Findings

Delivery of NSCs to the cytotoxic injured brain is limited by low cell survival rates post-transplantation and poor maintenance of native niche bioactive components. The use of biomaterial platforms can mimic in vivo the environment of the two germinal areas of the adult brain in which NSCs thrive. An environmental mimic that includes extracellular proteins and moieties, along with appropriate biomechanical cues has recently demonstrated promising results in enhancing neurogenesis, aiding the production of a bioengineered niche.

Summary

Biocomposition, biomechanics, and biostructure can be manipulated through engineered platforms to re-create the biofunctionality of an NSC niche. Upon transplantation and delivery with biomimetic scaffolds, NSCs show potential to promote functional recovery and rebuild neural circuitry post neurological trauma.

Keywords

Neural stem cell Engineered niche Neurogenesis Biomimetic microenvironment Tissue engineering 

Notes

Acknowledgments

Work from our laboratories was supported by NIH (R01EB016629-03).

Compliance with Ethical Standards

Conflict of Interest

Rita Matta and Anjelica Gonzalez each declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Cheung TH, Rando TA. Molecular regulation of stem cell quiescence. Nat Rev Mol Cell Biol. 2013;14(6):329–40.CrossRefGoogle Scholar
  2. 2.
    Codega P, Silva-Vargas V, Paul A, Maldonado-Soto AR, DeLeo AM, Pastrana E, et al. Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche. Neuron. 2014;82(3):545–59.CrossRefGoogle Scholar
  3. 3.
    Matta R, Gonzalez AL. Stroke repair via biomimicry of the subventricular zone. Front Mater. 2018;5(15).Google Scholar
  4. 4.
    Bond AM, Ming G-L, Song H. Adult mammalian neural stem cells and neurogenesis: five decades later. Cell Stem Cell. 2015;17(4):385–95.CrossRefGoogle Scholar
  5. 5.
    Sun GJ, Zhou Y, Stadel RP, Moss J, Yong JHA, Ito S, et al. Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain. Proc Natl Acad Sci. 2015;112(30):9484–9.CrossRefGoogle Scholar
  6. 6.
    Delgado AC, et al. Endothelial NT-3 delivered by vasculature and CSF promotes quiescence of subependymal neural stem cells through nitric oxide induction. Neuron. 2014;83(3):572–85.CrossRefGoogle Scholar
  7. 7.
    Stolp, H.B. and Z. Molnár, Neurogenic niches in the brain: help and hindrance of the barrier systems. Front Neurosci, 2015. 9(20).Google Scholar
  8. 8.
    • Trost A, et al. Brain and retinal pericytes: origin, function and role. Front Cell Neurosci. 2016;10(20) This article highlights pericytes in the neurovascular unit and their role in blood-brain barrier stability, focusing on their role in de- and regenerative processes. Google Scholar
  9. 9.
    Lacar B, Herman P, Platel JC, Kubera C, Hyder F, Bordey A. Neural progenitor cells regulate capillary blood flow in the postnatal subventricular zone. J Neurosci. 2012;32(46):16435–48.CrossRefGoogle Scholar
  10. 10.
    Lin R, Cai J, Nathan C, Wei X, Schleidt S, Rosenwasser R, et al. Neurogenesis is enhanced by stroke in multiple new stem cell niches along the ventricular system at sites of high BBB permeability. Neurobiol Dis. 2015;74:229–39.CrossRefGoogle Scholar
  11. 11.
    Ottone C, Krusche B, Whitby A, Clements M, Quadrato G, Pitulescu ME, et al. Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells. Nat Cell Biol. 2014;16(11):1045–56.CrossRefGoogle Scholar
  12. 12.
    Ashton RS, Conway A, Pangarkar C, Bergen J, Lim KI, Shah P, et al. Astrocytes regulate adult hippocampal neurogenesis through ephrin-B signaling. Nat Neurosci. 2012;15:1399–406.CrossRefGoogle Scholar
  13. 13.
    Mercier F. Fractones: extracellular matrix niche controlling stem cell fate and growth factor activity in the brain in health and disease. Cell Mol Life Sci. 2016;73(24):4661–74.CrossRefGoogle Scholar
  14. 14.
    Wade A, McKinney A, Phillips JJ. Matrix regulators in neural stem cell functions. Biochim Biophys Acta Gen Subj. 2014;1840(8):2520–5.CrossRefGoogle Scholar
  15. 15.
    Faissner A, Roll L, Theocharidis U. Tenascin-C in the matrisome of neural stem and progenitor cells. Mol Cell Neurosci. 2017;81:22–31.CrossRefGoogle Scholar
  16. 16.
    May M, et al. Cell tracking in vitro reveals that the extracellular matrix glycoprotein Tenascin-C modulates cell cycle length and differentiation in neural stem/progenitor cells of the developing mouse spinal cord. Biol Open. 2018;7(7).Google Scholar
  17. 17.
    Betancur MI, Mason HD, Alvarado-Velez M, Holmes PV, Bellamkonda RV, Karumbaiah L. Chondroitin sulfate glycosaminoglycan matrices promote neural stem cell maintenance and neuroprotection post-traumatic brain injury. ACS Biomater Sci Eng. 2017;3(3):420–30.CrossRefGoogle Scholar
  18. 18.
    Hatakeyama J, Wakamatsu Y, Nagafuchi A, Kageyama R, Shigemoto R, Shimamura K. Cadherin-based adhesions in the apical endfoot are required for active notch signaling to control neurogenesis in vertebrates. Development. 2014;141(8):1671–82.CrossRefGoogle Scholar
  19. 19.
    •• Regalado-Santiago C, et al. Mimicking neural stem cell niche by biocompatible substrates. Stem Cells Int. 2016;2016:1513285 This review examines NSCs in the neurogenic niche and their interactions with biocompatible substrates which mimic the in vivo microenvironmnet.CrossRefGoogle Scholar
  20. 20.
    Rammensee S, Kang MS, Georgiou K, Kumar S, Schaffer DV. Dynamics of mechanosensitive neural stem cell differentiation. Stem Cells. 2017;35(2):497–506.CrossRefGoogle Scholar
  21. 21.
    Ma Q, Yang L, Jiang Z, Song Q, Xiao M, Zhang D, et al. Three-dimensional stiff graphene scaffold on neural stem cells behavior. ACS Appl Mater Interfaces. 2016;8(50):34227–33.CrossRefGoogle Scholar
  22. 22.
    Li X, Liang H, Sun J, Zhuang Y, Xu B, Dai J. Electrospun collagen fibers with spatial patterning of SDF1α for the guidance of neural stem cells. Adv Healthcare Mater. 2015;4(12):1869–76.CrossRefGoogle Scholar
  23. 23.
    Arulmoli J, Wright HJ, Phan DTT, Sheth U, Que RA, Botten GA, et al. Combination scaffolds of salmon fibrin, hyaluronic acid, and laminin for human neural stem cell and vascular tissue engineering. Acta Biomater. 2016;43:122–38.CrossRefGoogle Scholar
  24. 24.
    Crapo PM, Tottey S, Slivka PF, Badylak SF. Effects of biologic scaffolds on human stem cells and implications for CNS tissue engineering. Tissue Eng A. 2014;20(1–2):313–23.CrossRefGoogle Scholar
  25. 25.
    •• Ghuman H, et al. Long-term retention of ECM hydrogel after implantation into a sub-acute stroke cavity reduces lesion volume. Acta Biomater. 2017;63:50–63 This article provides support for the use of natural biomaterials that can reduce further progression of a stroke cavity long-term and be utilied to deliver drugs or cells to the damaged area.CrossRefGoogle Scholar
  26. 26.
    Shin Y, Yang K, Han S, Park HJ, Seok Heo Y, Cho SW, et al. Reconstituting vascular microenvironment of neural stem cell niche in three-dimensional extracellular matrix. Adv Healthcare Mater. 2014;3(9):1457–64.CrossRefGoogle Scholar
  27. 27.
    Her GJ, Wu HC, Chen MH, Chen MY, Chang SC, Wang TW. Control of three-dimensional substrate stiffness to manipulate mesenchymal stem cell fate toward neuronal or glial lineages. Acta Biomater. 2013;9(2):5170–80.CrossRefGoogle Scholar
  28. 28.
    Thomas RC, Vu P, Modi SP, Chung PE, Landis RC, Khaing ZZ, et al. Sacrificial crystal templated hyaluronic acid hydrogels as biomimetic 3D tissue scaffolds for nerve tissue regeneration. ACS Biomater Sci Eng. 2017;3(7):1451–9.CrossRefGoogle Scholar
  29. 29.
    Fan L, Liu C, Chen X, Zou Y, Zhou Z, Lin C, et al. Directing induced pluripotent stem cell derived neural stem cell fate with a three-dimensional biomimetic hydrogel for spinal cord injury repair. ACS Appl Mater Interfaces. 2018;10(21):17742–55.CrossRefGoogle Scholar
  30. 30.
    Pietrucha K, Zychowicz M, Podobinska M, Buzanska L. Functional properties of different collagen scaffolds to create a biomimetic niche for neurally committed human induced pluripotent stem cells (iPSC). Folia Neuropathol. 2017;55(2):110–23.CrossRefGoogle Scholar
  31. 31.
    • Jenkins SI, et al. ‘Stealth’ nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics. J Control Release. 2016;224:136–45 This article discusses a well defined synthetic particle that can evade neural immune cells and major brain cell populations post transplantation, promoting the use of synthetic biomaterials for neurotherapeutic application.CrossRefGoogle Scholar
  32. 32.
    Vaysse L, Beduer A, Sol JC, Vieu C, Loubinoux I. Micropatterned bioimplant with guided neuronal cells to promote tissue reconstruction and improve functional recovery after primary motor cortex insult. Biomaterials. 2015;58:46–53.CrossRefGoogle Scholar
  33. 33.
    •• Davoust C, et al. Regenerative potential of primary adult human neural stem cells on micropatterned bio-implants boosts motor recovery. Stem Cell Res Ther. 2017;8(1):253 This article evaluates improvement in recovery post transplantation of NSCs in combination with implants. Evaluation with MRI and immunohistology provide insights into regenerative potential of cell-based biomaterial delivery.CrossRefGoogle Scholar
  34. 34.
    Hsieh F-Y, Lin H-H, Hsu S-h. 3D bioprinting of neural stem cell-laden thermoresponsive biodegradable polyurethane hydrogel and potential in central nervous system repair. Biomaterials. 2015;71:48–57.CrossRefGoogle Scholar
  35. 35.
    Cherry JF, Bennett NK, Schachner M, Moghe PV. Engineered N-cadherin and L1 biomimetic substrates concertedly promote neuronal differentiation, neurite extension and neuroprotection of human neural stem cells. Acta Biomater. 2014;10(10):4113–26.CrossRefGoogle Scholar
  36. 36.
    Yun D, Lee YM, Laughter MR, Freed CR, Park D. Substantial differentiation of human neural stem cells into motor neurons on a biomimetic Polyurea. Macromol Biosci. 2015;15(9):1206–11.CrossRefGoogle Scholar
  37. 37.
    Lee I-C, Wu YC, Cheng EM, Yang WT. Biomimetic niche for neural stem cell differentiation using poly-L-lysine/hyaluronic acid multilayer films. J Biomater Appl. 2015;29(10):1418–27.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringYale UniversityNew HavenUSA

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