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Gezielte dreidimensionale Zellausrichtung und -elongation in artifiziellen Geweben

Directed 3D cell alignment and elongation in engineered tissues

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Zeitschrift für Herz-,Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Anordnung und Ausrichtung von Zellen sind entscheidend für die biologische Funktion von Geweben. Obwohl eine Vielzahl von Techniken beschrieben worden sind, um die Ausrichtung von Zellen zweidimensional zu steuern, bleibt es weiterhin eine immense Herausforderung, die Zellausrichtung von komplex organisierten nativen Geweben innerhalb von in vitro gezüchteten dreidimensionalen Geweben zu rekapitulieren. In der Vergangenheit bedurfte es einer aufwendigen, externen physikalischen Stimulation – beispielsweise mittels elektrischer oder mechanischer Reize –, um Ausrichtung und Elongation verschiedener Zelltypen nativer Gewebe innerhalb einer künstlichen 3D-Matrix zu simulieren. Neuere Studien konnten jedoch zeigen, dass es auch mit technisch simpleren Methoden, z. B. durch Vorgabe der 3D-Mikrogeometrie mithilfe von sog. Micropatterning-Techniken, möglich ist, Zellausrichtung und -elongation in vitro gezielt zu kontrollieren. Dies erlaubt uns nicht nur die dreidimensionale Zell-zu-Gewebe-Morphogenese besser zu verstehen, sondern stellt uns auch ein weiteres wichtiges Werkzeug zur Züchtung bioartifizieller Gewebe zur Verfügung.

Abstract

Cell orientation and alignment is crucial for the biological function of tissues. Although a multitude of techniques have been described to control cellular alignment in 2D, recapitulating the cellular alignment of highly organized native tissues within in vitro engineered 3D tissues still remains a major challenge. In the past it required elaborate external physical stimulation, e.g., by means of mechanical or electrical stimuli, in order to recapitulate the alignment and elongation of different cell types within an artificial 3D matrix. However, recent studies were able to show that cellular alignment and elongation can also be selectively controlled in vitro through simpler technical methods, e.g., by presetting the 3D microgeometry using micropatterning techniques. This not only allows us to better understand the 3D cell-to-tissue morphogenesis, but also provides us with another important tool for the engineering of bioartificial tissues.

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Literatur

  1. Papadaki M, Bursac N, Langer R et al (2001) Tissue engineering of functional cardiac muscle: Molecular, structural, and electrophysiological studies. Am J Physiol Heart Circ Physiol 280(1):H168–178

    PubMed  CAS  Google Scholar 

  2. Khademhosseini A, Vacanti JP, Langer R (2009) Progress in tissue engineering. Sci Am 300(5):64–71

    Article  PubMed  CAS  Google Scholar 

  3. Akhyari P, Fedak PW, Weisel RD et al (2002) Mechanical stretch regimen enhances the formation of bioengineered autologous cardiac muscle grafts. Circulation 106(12 Suppl 1):I137–142

    Article  PubMed  Google Scholar 

  4. Nguyen TD, Liang R, Woo SL et al (2009) Effects of cell seeding and cyclic stretch on the fiber remodeling in an extracellular matrix-derived bioscaffold. Tissue Eng Part A 15(4):957–963

    Article  PubMed  CAS  Google Scholar 

  5. Vader D, Kabla A, Weitz D, Mahadevan L (2009) Strain-Induced alignment in collagen gels. Plos One 4(6):e5902

    Article  PubMed  Google Scholar 

  6. Radisic M, Park H, Shing H et al (2004) Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds. Proc Natl Acad Sci U S A 101(52):18129–18134

    Article  PubMed  CAS  Google Scholar 

  7. Flaibani M, Boldrin L, Cimetta E et al (2009) Muscle differentiation and myotubes alignment is influenced by micropatterned surfaces and exogenous electrical stimulation. Tissue Eng Part A 15(9):2447–2457

    Article  PubMed  CAS  Google Scholar 

  8. Tandon N, Cannizzaro C, Chao PH et al (2009) Electrical stimulation systems for cardiac tissue engineering. Nat Protoc 4(2):155–173

    Article  PubMed  CAS  Google Scholar 

  9. Khademhosseini A, Langer R, Borenstein J, Vacanti JP (2006) Microscale technologies for tissue engineering and biology. Proc Natl Acad Sci U S A 103(8):2480–2487

    Article  PubMed  CAS  Google Scholar 

  10. Chen CS, Mrksich M, Huang S et al (1997) Geometric control of cell life and death. Science 276(5317):1425–8

    Article  PubMed  CAS  Google Scholar 

  11. McBeath R, Pirone DM, Nelson CM et al (2004) Cell shape, cytoskeletal tension, and rhoa regulate stem cell lineage commitment. Dev Cell 6(4):483–495

    Article  PubMed  CAS  Google Scholar 

  12. Murtuza B, Nichol JW, Khademhosseini A (2009) Micro- and nanoscale control of the cardiac stem cell niche for tissue fabrication. Tissue Eng Part B Rev 15(4):443–454

    Article  PubMed  Google Scholar 

  13. Burdick JA, Vunjak-Novakovic G (2009) Engineered microenvironments for controlled stem cell differentiation. Tissue Eng Part A 15(2):205–219

    Article  PubMed  CAS  Google Scholar 

  14. Nelson CM, Chen CS (2002) Cell-Cell signaling by direct contact increases cell proliferation via a pi3k-dependent signal. FEBS Lett 514(2–3):238–42.

    Google Scholar 

  15. Nelson CM, Liu WF, Chen CS (2007) Manipulation of cell-cell adhesion using bowtie-shaped microwells. Methods Mol Biol 3701–3710

  16. Khademhosseini A, Eng G, Yeh J et al (2007) Microfluidic patterning for fabrication of contractile cardiac organoids. Biomed Microdevices 9(2):149–157

    Article  PubMed  Google Scholar 

  17. Lee WG, Kim YG, Chung BG et al (2010) Nano/Microfluidics for diagnosis of infectious diseases in developing countries. Adv Drug Deliv Rev 62(4–5):449–457

    Google Scholar 

  18. Seidi A, Kaji H, Annabi N et al (2011) A microfluidic-based neurotoxin concentration gradient for the generation of an in vitro model of Parkinson’s disease. Biomicrofluidics 5(2):22214

    Article  PubMed  Google Scholar 

  19. Aubin H, Nichol JW, Hutson CB et al (2010) Directed 3D cell alignment and elongation in microengineered hydrogels. Biomaterials 31(27):6941–6951

    Article  PubMed  CAS  Google Scholar 

  20. Nichol JW, Koshy ST, Bae H et al (2010) Cell-Laden microengineered gelatin methacrylate hydrogels. Biomaterials 31(21):5536–5544

    Article  PubMed  CAS  Google Scholar 

  21. Klebe RJ, Caldwell H, Milam S (1989) Cells transmit spatial information by orienting collagen fibers. Matrix 9(6):451–458

    Article  PubMed  CAS  Google Scholar 

  22. Ott HC, Matthiesen TS, Goh SK et al (2008) Perfusion-Decellularized matrix: Using nature’s platform to engineer a bioartificial heart. Nat Med 14(2):213–221

    Article  PubMed  CAS  Google Scholar 

  23. Akhyari P, Aubin H, Gwanmesia P et al (2011) The quest for an optimized protocol for whole-heart decellularization: a comparison of three popular and a novel decellularization technique and their diverse effects on crucial extracellular matrix qualities. Tissue Eng Part C Methods 17(9):915–926

    Article  PubMed  CAS  Google Scholar 

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Correspondence to H. Aubin.

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Basierend auf der Arbeit „Directed 3D cell alignment and elongation in microengineered hydrogels“ von H. Aubin et al. [19], die mit dem Ernst-Rainer de Vivie Nachwuchsförderpreis 2012 der DGTHG ausgezeichnet wurde.

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Aubin, H., Akhyari, P., Khademhosseini, A. et al. Gezielte dreidimensionale Zellausrichtung und -elongation in artifiziellen Geweben. Z Herz- Thorax- Gefäßchir 26, 188–195 (2012). https://doi.org/10.1007/s00398-012-0924-8

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  • DOI: https://doi.org/10.1007/s00398-012-0924-8

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