Implantable microenvironments to attract hematopoietic stem/cancer cells

Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19638-43. doi: 10.1073/pnas.1208384109. Epub 2012 Nov 12.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Hydrogels