Fate Distribution and Regulatory Role of Human Mesenchymal Stromal Cells in Engineered Hematopoietic Bone Organs

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The generation of humanized ectopic ossicles (hOss) in mice has been proposed as an advanced translational and fundamental model to study the human hematopoietic system. The approach relies on the presence of human bone marrow-derived mesenchymal stromal cells (hMSCs) supporting the engraftment of transplanted human hematopoietic stem and progenitor cells (HSPCs). However, the functional distribution of hMSCs within the humanized microenvironment remains to be investigated. Here, we combined genetic tools and quantitative confocal microscopy to engineer and subsequently analyze hMSCs′ fate and distribution in hOss. Implanted hMSCs reconstituted a humanized environment including osteocytes, osteoblasts, adipocytes, and stromal cells associated with vessels. By imaging full hOss, we identified rare physical interactions between hMSCs and human CD45+/CD34+/CD90+ cells, supporting a functional contact-triggered regulatory role of hMSCs. Our study highlights the importance of compiling quantitative information from humanized organs, to decode the interactions between the hematopoietic and the stromal compartments. Biological Sciences; Stem Cells Research; Tissue Engineering


  • Paul E. Bourgine
  • Kristin Fritsch
  • Sebastien Pigeot
  • Hitoshi Takizawa
  • Leo Kunz
  • Konstantinos D. Kokkaliaris
  • Daniel L. Coutu
  • Markus G. Manz
  • Ivan Martin
  • Timm Schroeder
Enheter & grupper
Externa organisationer
  • ETH Zürich
  • University of Basel
  • University Hospital Basel
  • University Hospital of Zurich
  • Kumamoto University
  • University of Zurich

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi


Sidor (från-till)504-513
Antal sidor10
StatusPublished - 2019 sep 27
Peer review utfördJa