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Operating and Biocontainment Procedures of a Facility for Laboratory Mice with a Natural Microbiome: Immunophenotyping Procedure
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Multiple genetically engineered humanized microenvironments in a single mouse.

Jungwoo Lee1, Dirk Heckl2, Biju Parekkadan3

  • 1Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital & Harvard Medical School and Shriners Hospital for Children, Boston, MA USA ; Department of Chemical Engineering, Institute for Applied Life Sciences, University of Massachusetts, Amherst, MA USA.

Biomaterials Research
|June 30, 2016
PubMed
Summary
This summary is machine-generated.

This study developed a novel mouse model using biomaterial implants to create localized human cytokine microenvironments. This platform enables the study of human stem cell engraftment and differentiation in vivo.

Keywords:
Bone marrow stromal cellsChimeric mouse modelGenetically engineered stromaHuman hematopoietic stem and progenitor cellsImplantable microenvironmentsScaffolds

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Area of Science:

  • Biomedical Engineering
  • Stem Cell Biology
  • Immunology

Background:

  • Immunodeficient mouse models are crucial for human stem cell research.
  • Previous models faced limitations in studying localized human cell behavior.
  • This study aimed to engineer specific microenvironments for human cell studies.

Purpose of the Study:

  • To create a novel in vivo system for studying human CD34+ hematopoietic stem/progenitor cell (HSPC) engraftment and differentiation.
  • To engineer localized microenvironments within a single mouse using biomaterial implants and genetically engineered stromal cells.
  • To investigate the effects of specific human cytokines on HSPC behavior.

Main Methods:

  • Utilized subdermal biomaterial implants seeded with genetically engineered stromal cells.
  • Engineered stromal cells to overexpress specific human cytokines: Vascular Endothelial Growth Factor A (hVEGFa), Stromal Derived Factor 1 Alpha (hSDF1a), or Tumor Necrosis Factor Alpha (hTNFa).
  • Controlled stromal cell growth to minimize systemic cytokine exposure, creating autonomous local sites.

Main Results:

  • Successfully created localized microenvironments expressing specific human cytokines within a single mouse.
  • Demonstrated minimized systemic exposure of locally overexpressed cytokines.
  • Validated that engineered factors had bioactive effects on human CD34+ hematopoietic progenitor cell differentiation.
  • Enabled local analysis of cytokine effects on hematopoietic stem cell recruitment, engraftment, and differentiation in four distinct tissue microenvironments.

Conclusions:

  • The developed model system provides a new platform for in vivo validation studies.
  • Facilitates the study of multiple human proteins and their local effects on hematopoietic cell biology.
  • Offers a powerful tool for advancing human stem cell research.