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

Research output: Contribution to journalArticle

Abstract

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

Details

Authors
  • Paul E. Bourgine
  • Kristin Fritsch
  • Sebastien Pigeot
  • Hitoshi Takizawa
  • Leo Kunz
  • Konstantinos D. Kokkaliaris
  • Daniel L. Coutu
  • Markus G. Manz
  • Ivan Martin
  • Timm Schroeder
Organisations
External organisations
  • ETH Zürich
  • University of Basel
  • University Hospital Basel
  • University Hospital of Zurich
  • Kumamoto University
  • University of Zurich
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • Biological Sciences, Stem Cells Research, Tissue Engineering
Original languageEnglish
Pages (from-to)504-513
Number of pages10
JournaliScience
Volume19
Publication statusPublished - 2019 Sep 27
Publication categoryResearch
Peer-reviewedYes