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Improved Stem Cell Therapeutics via an in vitro Stem Cell Niche Model?

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Review of “A Quiescent, Regeneration-Responsive Tissue Engineered Mesenchymal Stem Cell Bone Marrow Niche Model via Magnetic Levitation” from ACS Nano by Stuart P. Atkinson

Studying the stem cell niche in the human bone marrow is no mean feat, but we currently lack an in vitro model which recapitulates all known in vivo niche characteristics. However, an exciting new study from the laboratory of Catherine Berry (Glasgow University, UK) may now have changed this using a new magnet-based strategy.

In their new study in ACS Nano, Lewis et al describe a simple and quick assembly protocol for an in vitro bone marrow-like niche based on nanomagnetically levitated mesenchymal stem cells (MSCs) [1]. This new strategy may permit a more detailed analysis of the stem cell niche and, therefore, the generation of enhanced stem cell therapeutics.

To form the niche model, the authors employed superparamagnetic nanoparticle (SPION)-labelled MSCs and an external magnet to create a levitating multicellular spheroid culture [2, 3]. A short incubation period created spheroids of around 300 mm in diameter which could be maintained for around 14 days. Transfer of the spheroids to a soft collagen gel with bone marrow-like low-level of elasticity completed the niche model, and, as observed in the in vivo niche, the spheroid MSCs remained quiescent, expressed MSC markers (NES and STRO-1), and retained their multilineage differentiation capacity. 

Excellent stuff! But how do these react and contribute to tissue repair? Encouragingly, the spheroid-derived MSCs functioned in a similar manner to bone marrow-derived MSCs in a simple wound healing model. Once placed into the wound, spheroid MSCs migrated (in response to interleukin-6 expression), grafted, and differentiated into appropriate cell types to support tissue regeneration.

This simple, efficient, and cost-effective strategy to form a bone fide in vitro bone marrow niche will undoubtedly lead to further exciting research findings. While the nanoparticles are useful for spheroid aggregation, we can also use them to track cells to discover more about stem cell-niche interactions, stem cell migration, and stem cell engraftment into injured tissues. All this information may lead to a better understanding of in vivo stem cell-based repair and regeneration and the construction of enhanced stem cell therapeutics.

References

  1. Lewis EE, Wheadon H, Lewis N, et al. A Quiescent, Regeneration-Responsive Tissue Engineered Mesenchymal Stem Cell Bone Marrow Niche Model via Magnetic Levitation. ACS Nano 2016;10:8346-8354.
  2. Bartosh TJ, Ylostalo JH, Mohammadipoor A, et al. Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Proc Natl Acad Sci U S A 2010;107:13724-13729.
  3. Souza GR, Molina JR, Raphael RM, et al. Three-dimensional tissue culture based on magnetic cell levitation. Nat Nanotechnol 2010;5:291-296.