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Synthetic Immunology pp 181–200Cite as

Engineering of Artificial Lymph Node

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Abstract

Synthetic immunology has been a topic of research in both the immunology and tissue engineering fields. Since the first successful generation of an artificial lymph node (LN) in vivo by implantation of a collagen scaffold with stromal cells has been reported, tissue engineering of artificial LNs using several biological and engineering techniques has started. Recently, the advance engineering approaches using several manufacturing machines, including three-dimensional (3D) printers, 3D fabrication and assembling machines, have been addressed. Such approaches are in general called “Biofabrication”. As the use of machines has several potential capabilities, such as super-manufacturing beyond the capability of humans, direct tissue manufacturing by additive manufacturing and computer aided tissue engineering by applying high efficiency of the computer and digital technologies, the strategy of biofabrication can provide a potential of breakthrough to construct highly sophisticated 3D scaffolds and to generate several complex 3D tissues and organs. Based on this concept, we have ever developed several machines for this purpose such as an inkjet 3D bioprinter to construct complex and multi-composite 3D structures. In the present work, we applied this strategy to rationally design and construct artificial LNs. This research is still in its infancy, and it requires several improvements in terms of new technology. Here, we introduced our struggles and current works towards production of practical artificial LNs.

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Abbreviations

LN:

Lymph node

2D:

two dimension or two dimensional

3D:

three dimension or three dimensional

CAD:

computer aided design

CAM:

Computer aided manufacturing

CAE:

Computer aided engineering

AM:

Additive Manufacturing

FDM:

fused deposition modeling

UV:

Ultra violet

PGA:

polyglycolic acid

PLA:

polylactic acid

PCL:

poly-caprolactone

SLOs:

secondary lymphoid organs

TLOs:

tertiary lymphoid organs

LTo:

lymphoid tissue organizer

LTi:

lymphoid tissue inducer

VCAM-1:

vascular cell adhesion molecule-1

DC:

dendritic cell

FDC:

follicular dendritic cell

EC:

endothelial cell

SCID mouse:

severe combined immunodeficiency mouse

ECM:

Extracellular Matrix

MEMS:

Micro Electro Mechanical Systems

GF:

Growth factor

References

  • Ansel KM, Ngo VN, Hyman PL, Luther SA, Förster R, Sedgwick JD, Browning JL, Lipp M, Cyster JG (2000) A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 406(6793):309–314

    Article  CAS  PubMed  Google Scholar 

  • Bajaj P, Schweller RM, Khademhosseini A, West JL, Bashir R (2014) 3D biofabrication strategies for tissue engineering and regenerative medicine. Annu Rev Biomed Eng 16:247–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cupedo T, Stroock A, Coles M (2012) Application of tissue engineering to the immune system: development of artificial lymph nodes. Front Immunol 3:343

    Article  PubMed  PubMed Central  Google Scholar 

  • Faulkner-Jones A, Greenhough S, King JA, Gardner J, Courtney A, Shu W (2013) Development of a valve-based cell printer for the formation of human embryonic stem cell spheroid aggregates. Biofabrication 5(1):015013

    Article  PubMed  Google Scholar 

  • Geering B, Fussenegger M (2015) Synthetic immunology: modulating the human immune system. Trends Biotechnol 33(2):65–79

    Article  CAS  PubMed  Google Scholar 

  • Griffith LG, Naughton G (2002) Tissue engineering-current challenges and expanding opportunities. Science 295(5557):1009–1014

    Article  CAS  PubMed  Google Scholar 

  • Guillemot F, Mironov V, Nakamura M (2010) Bioprinting is coming of age: report from the International Conference on Bioprinting and Biofabrication in Bordeaux (3B’09). Biofabrication 2(1):010201–010207

    Article  PubMed  Google Scholar 

  • Hutmacher DW, Sittinger M, Risbud MV (2004) Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems. Trends Biotechnol 7:354–362

    Article  Google Scholar 

  • Jakab K, Neagu A, Mironov V, Markwald RR, Forgacs G (2004) Engineering biological structures of prescribed shape using self-assembling multicellular systems. PNAS 101:2864–2869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jakab K, Damon B, Neagu A, Kachurin A, Forgacs G (2006) Three-dimensional tissue constructs built by bioprinting. Biorheology 43:509–513

    PubMed  Google Scholar 

  • Kamimura W, Hattori R, Koyama H, Miyata T, Takato T (2012) A calcium-cross-linked hydrogel based on alginate-modified atelocollagen functions as a scaffold material. J Biomater Sci Polym Ed 23(5):609–628

    Article  CAS  PubMed  Google Scholar 

  • Khetani SR, Bhatia SN (2006) Engineering tissues for in vitro applications. Curr Opin Biotechnol 17(5):524–531

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi Y, Watanabe T (2010) Synthesis of artificial lymphoid tissue with immunological function. Trends Immunol 31(11):422–428

    Article  CAS  PubMed  Google Scholar 

  • Langer R, Vacanti JP (1993) Tissue engineering. Science 260(5110):920–926

    Article  CAS  PubMed  Google Scholar 

  • Leong KF, Chuaa CK, Sudarmadjia N, Yeonga WY (2008) Engineering functionally graded tissue engineering scaffolds. J Mech Behav Biomed Mater 1(2):140–152

    Article  CAS  PubMed  Google Scholar 

  • Mironov V, Boland T, Trusk T, Forgacs G, Markward RR (2003) Organ printing: computer-aided jet-based 3D tissue engineering. Trends Biotechnol 21(4):157–161

    Article  CAS  PubMed  Google Scholar 

  • Mironov V, Reis N, Derby B (2006) Bioprinting: a beginning. Tissue Eng 12(4):631–634

    Article  PubMed  Google Scholar 

  • Mironov V, Trusk T, Kasyanov V, Little S, Swaja R, Markwald R (2009) Biofabrication: a 21st century manufacturing paradigm. Biofabrication 1(2):022001

    Article  CAS  PubMed  Google Scholar 

  • Nakamura M (2010) Reconstruction of biological three-dimensional tissues: bioprinting and biofabrication using inkjet technology. In: Ringersen BR, Spargo BJ, Wu P (eds) Part II: inkjet approaches, cell and organ printing. Springer, Heidelberg, pp 23–34

    Chapter  Google Scholar 

  • Nakamura M (2013) Tissue engineering, a case study. In: Hutchings IM, Martin GD (eds) Inkjet technology for digital fabrication. Wiley, West Sussex, pp 307–324

    Google Scholar 

  • Nakamura M, Kobayashi A, Takagi F, Watanabe A, Hiruma Y, Ohuchi K, Iwasaki Y, Horie M, Morita I, Takatani S (2005) Biocompatible inkjet printing technique for designed seeding of individual living cells. Tissue Eng 11:1658–1666

    Article  CAS  PubMed  Google Scholar 

  • Nakamura M, Arai K, Toda H (2012) J Soc Instrum Control Eng 51(10):907–911. (Japanese)

    Google Scholar 

  • Nishiyama Y, Nakamura M, Henmi C, Yamaguchi K, Mochizuki S, Nakagawa H, Takiura K (2009) Development of three-dimensional bio-printer: construction of cell supporting structures using hydrogel and state-of-the-art inkjet technology. J Biomech Eng 131(3):035001

    Article  PubMed  Google Scholar 

  • Okamoto N, Chihara R, Shimizu C, Nishimoto S, Watanabe T (2007) Artificial lymph nodes induce potent secondary immune responses in naive and immunodeficient mice. J Clin Invest 17(4):997–1007

    Article  Google Scholar 

  • Spiegel DA (2010) Grand challenge commentary: synthetic immunology to engineer human immunity. Nat Chem Biol 6(12):871–872

    Article  CAS  PubMed  Google Scholar 

  • Suematsu S, Watanabe T (2004) Generation of a synthetic lymphoid tissue–like organoid in mice. Nat Biotechnol 22(12):1539–1545

    Article  CAS  PubMed  Google Scholar 

  • Sun W (2009) Welcome to biofabrication. Biofabrication 1(1):010201

    Article  Google Scholar 

  • Sun W, Lal P (2004) Recent development on computer aided tissue engineering: overview, scope and challenges. Biotechnol Appl Biochem 39:29–47

    Article  CAS  PubMed  Google Scholar 

  • van de Pavert SA, Olivier BJ, Goverse G, Vondenhoff MF, Greuter M, Beke P, Kusser K, Höpken UE, Lipp M, Niederreither K, Blomhoff R, Sitnik K, Agace WW, Randall TD, de Jonge WJ, Mebius RE (2009) Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation. Nat Immunol 10(11):1193–1199

    Article  PubMed  PubMed Central  Google Scholar 

  • Vozzi G, Previti A, De Rossi D, Ahluwalia A (2002) Microsyringe-based deposition of two-dimensional and three-dimensional polymer scaffolds with a well-defined geometry for application to tissue engineering. Tissue Eng 8:1089–1098

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the members of the artificial LN project team at Nakamura Laboratory at the University of Toyama and the staff of Kasen Nozzle Mfg. Co. Ltd. for help with the experiments using the spinneret nozzle. We would also like to thank the members of the Grant-in-Aid for Scientific Research on Innovative Areas “Analysis and Synthesis of Multidimensional Immune Organ Network” for important information regarding synthetic immunology. In addition, we express our thanks to Musashi Engineering Inc. and Leica Microsystems K.K. for kindly offering photographs and their kind support for obtaining images. For Fig. 9.9, we are thankful to Professor Shiro Mizoguchi a honorary professor of Kobe University for giving permission of use a figure of the data base of histology of Kobe Gakuin University.

This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas “Hyper Bio Assembler for 3D Cellular Innovation” (no. 26106713) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), and A-STEP (Adaptable & Seamless Technology Transfer Program through Target-driven R&D) from the Japan Science and Technology Agency (no. AS242170P).

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Authors and Affiliations

  1. Graduate School of Science and Engineering for Research, University of Toyama, Toyama, Japan

    Makoto Nakamura M.D., Ph.D., Kenichi Arai, Takahito Mimura, Jungo Tagawa, Hirotoshi Yoshida & Tadashi Nakaji-Hirabayashi

  2. Institute of Biomedical and Health Sciences, Hiroshima University, Higashihiroshima, Japan

    Koichi Kato

  3. Medical Research Institute, Kitano Hospital, Osaka, Japan

    Yuka Kobayashi & Takeshi Watanabe

Authors
  1. Makoto Nakamura M.D., Ph.D.
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  2. Kenichi Arai
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  3. Takahito Mimura
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  4. Jungo Tagawa
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  5. Hirotoshi Yoshida
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  6. Koichi Kato
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  7. Tadashi Nakaji-Hirabayashi
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  8. Yuka Kobayashi
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  9. Takeshi Watanabe
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Corresponding author

Correspondence to Makoto Nakamura M.D., Ph.D. .

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Editors and Affiliations

  1. Kitano Hospital, Kita-ku, Osaka, Japan

    Takeshi Watanabe

  2. Division of Experimental Immunology, University of Tokushima, Tokushima, Japan

    Yousuke Takahama

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Nakamura, M. et al. (2016). Engineering of Artificial Lymph Node. In: Watanabe, T., Takahama, Y. (eds) Synthetic Immunology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56027-2_9

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