Implantable microenvironments to attract hematopoietic stem/cancer cells

Jungwoo Lee, Matthew Li, Jack Milwid, Joshua Dunham, Claudio Vinegoni, Rostic Gorbatov, Yoshiko Iwamoto, Fangjing Wang, Keyue Shen, Kimberley Hatfield, Marianne Enger, Sahba Shafiee, Emmet McCormack, Benjamin L Ebert, Ralph Weissleder, Martin L Yarmush, Biju Parekkadan

Research output: Contribution to journalArticlepeer-review

Abstract

The environments that harbor hematopoietic stem and progenitor cells are critical to explore for a better understanding of hematopoiesis during health and disease. These compartments often are inaccessible for controlled and rapid experimentation, thus limiting studies to the evaluation of conventional cell culture and transgenic animal models. Here we describe the manufacture and image-guided monitoring of an engineered microenvironment with user-defined properties that recruits hematopoietic progenitors into the implant. Using intravital imaging and fluorescence molecular tomography, we show in real time that the cell homing and retention process is efficient and durable for short- and long-term engraftment studies. Our results indicate that bone marrow stromal cells, precoated on the implant, accelerate the formation of new sinusoidal blood vessels with vascular integrity at the microcapillary level that enhances the recruitment hematopoietic progenitor cells to the site. This implantable construct can serve as a tool enabling the study of hematopoiesis.

Original languageEnglish
Pages (from-to)19638-43
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number48
DOIs
Publication statusPublished - 27 Nov 2012

Keywords

  • Animals
  • Extracellular Matrix
  • Hematopoietic Stem Cells/cytology
  • Humans
  • Hydrogels
  • Mice
  • Mice, Inbred NOD
  • Mice, Nude
  • Microscopy, Confocal
  • Neoplasms/pathology
  • Stem Cell Niche
  • Tissue Scaffolds
  • Tomography/methods
  • Tumor Microenvironment

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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