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Stem Cell Mobilization pp 85–95Cite as

A Microcavity Array-Based 3D Model System of the Hematopoietic Stem Cell Niche

Part of the Methods in Molecular Biology book series (MIMB,volume 2017)

Abstract

Despite huge advances in recent years, the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niches in the bone marrow is still far from being fully understood. One reason is that hematopoiesis is a multi-step maturation process leading to HSPC heterogeneity. Subpopulations of HSPCs can be identified by clonogenic assays or in serial transplantation experiments in mice following sublethal irradiation, but it is very complex to reproduce or even maintain stem cell plasticity in vitro. Advanced model systems have been developed that allow to precisely control and analyze key components of the physiologic microenvironment for not only fundamental research purposes but, as a long-term goal, also for clinical applications. In this chapter, we describe our approach of building an artificial hematopoietic stem cell niche in the form of polymer film-based microcavities with a diameter of 300 μm and a depth of up to 300 μm and arranged in a 634-cavity array. The polymer films are provided with 3 μm pores and thus allow perfusion of the culture medium. The microcavity arrays can be inserted into a microbioreactor where a closed circulation loop can be tightly controlled with regard to medium flow and gas supply. The microcavity arrays were used for a three-dimensional (3D) co-culture of MSCs and HSPCs in a defined ratio over a time period of up to 21 days. With this setup, it could be demonstrated that the HSPCs maintained their stem cell characteristics more efficiently as compared to conventional monolayer co-culture controls.

Key words

  • Microthermoforming
  • Microcavity array
  • MSC-HSPC co-culture
  • Perfusion
  • Microbioreactor

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Authors and Affiliations

  1. Institute of Functional Interfaces, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany

    Eric Gottwald & Cordula Nies

  2. Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Patrick Wuchter

  3. German Red Cross Blood Service Baden-Württemberg — Hessen, Maastricht, The Netherlands

    Patrick Wuchter & Rainer Saffrich

  4. Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Rainer Saffrich

  5. Department of Medicine V (Hematology, Oncology, Rheumatology), Heidelberg University, Heidelberg, Germany

    Rainer Saffrich

  6. Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands

    Roman Truckenmüller & Stefan Giselbrecht

Authors
  1. Eric Gottwald
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  2. Cordula Nies
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  3. Patrick Wuchter
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  4. Rainer Saffrich
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  5. Roman Truckenmüller
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  6. Stefan Giselbrecht
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Corresponding author

Correspondence to Eric Gottwald .

Editor information

Editors and Affiliations

  1. Department of Internal Medicine II, Center for Medical Research, University of Tübingen, Tübingen, Germany

    Gerd Klein

  2. Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Patrick Wuchter

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Gottwald, E., Nies, C., Wuchter, P., Saffrich, R., Truckenmüller, R., Giselbrecht, S. (2019). A Microcavity Array-Based 3D Model System of the Hematopoietic Stem Cell Niche. In: Klein, G., Wuchter, P. (eds) Stem Cell Mobilization. Methods in Molecular Biology, vol 2017. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9574-5_7

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  • DOI: https://doi.org/10.1007/978-1-4939-9574-5_7

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9573-8

  • Online ISBN: 978-1-4939-9574-5

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