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Bone marrow transplant is a potential cure for several diseases, including cancer and specific genetic disorders. Notably, this procedure is applicable for patients suffering from aplastic anemia, certain types of leukemia, severe combined immunodeficiency disease (SCID), Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, thalassemia, sickle-cell disease, and certain cancers.
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Related Experiment Video

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A Three-dimensional Tissue Culture Model to Study Primary Human Bone Marrow and its Malignancies
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Development of a 3D bone marrow adipose tissue model.

Heather Fairfield1, Carolyne Falank1, Mariah Farrell1

  • 1Maine Medical Center Research Institute, Scarborough, ME 04074, USA; University of Maine Graduate School of Biomedical Science and Engineering, Orono, ME 04469, USA; Tufts University School of Medicine, Boston, MA 02111, USA.

Bone
|January 26, 2018
PubMed
Summary

Researchers developed the first 3D bone marrow adipose tissue (BMAT) model using mesenchymal stromal cells (MSCs). This advanced model mimics in vivo conditions, enabling better study of BMAT and its interactions with myeloma cells for therapeutic target discovery.

Keywords:
3DBone marrow adiposeMultiple myelomaSilk scaffoldsTissue engineering

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A Human Bone Marrow 3D Model to Investigate the Dynamics and Interactions Between Resident Cells in Physiological or Tumoral Contexts
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Area of Science:

  • Biomedical Engineering
  • Tissue Engineering
  • Cancer Biology

Background:

  • Two-dimensional (2D) in vitro models lack the physiological relevance of in vivo systems, limiting data reliability for drug screening and disease modeling.
  • Three-dimensional (3D) in vitro models offer improved recapitulation of tissue structures and cellular functions, bridging the gap between 2D cultures and in vivo studies.
  • Bone marrow adipose tissue (BMAT), a systemically relevant endocrine-signaling depot, has lacked a dedicated in vitro model for research.

Purpose of the Study:

  • To develop and validate the first 3D in vitro model of bone marrow adipose tissue (BMAT) using human or mouse bone marrow mesenchymal stromal cells (MSCs).
  • To assess the stability and utility of the 3D BMAT model for co-culture with myeloma cells.
  • To investigate the interactions between BMAT and myeloma cells within a 3D microenvironment and compare its inflammatory profile to 2D cultures.

Main Methods:

  • Development of a 3D culture system using bone marrow mesenchymal stromal cells (MSCs) to engineer bone marrow adipose tissue (BMAT).
  • Co-culture of the 3D BMAT model with myeloma cell lines (5TGM1, OPM2, MM1S) for up to two weeks.
  • Proteomic characterization, microarray analysis (>22,000 genes), KEGG pathway analysis, and gene set enrichment analysis (GSEA) to assess the model's biological state.

Main Results:

  • The 3D BMAT model was stably cultured in vitro for at least three months.
  • Myeloma cells could be cultured on the 3D BMAT model for at least two weeks, inducing delipidation in BMAT adipocytes, suggesting bidirectional interactions.
  • Proteomic and gene expression analyses indicated that the 3D BMAT model exhibited a less inflammatory profile compared to 2D cultures.

Conclusions:

  • The developed 3D BMAT model is the first of its kind, offering a physiologically relevant platform for studying bone marrow microenvironment.
  • This versatile model facilitates the investigation of interactions between BMAT and malignant cells, potentially identifying novel therapeutic targets.
  • The 3D BMAT model provides a more realistic and 'healthier' in vitro system for understanding bone marrow diseases and biological processes.