4.8 Article

Implantable microenvironments to attract hematopoietic stem/cancer cells

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1208384109

Keywords

hydrogel scaffolds; leukemia; mesenchymal stem cells; stem cell niche; tissue engineered bone marrow

Funding

  1. National Institutes of Health [R01EB012521, K01DK087770]
  2. Bergen Research Foundation
  3. Norwegian Cancer Society
  4. Shriners Hospitals for Children
  5. National Cancer Institute [1K99CA163671-01A1]

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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 micro-capillary level that enhances the recruitment hematopoietic progenitor cells to the site. This implantable construct can serve as a tool enabling the study of hematopoiesis.

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