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

Bourgine, Paul E. LU ; Fritsch, Kristin; Pigeot, Sebastien; Takizawa, Hitoshi; Kunz, Leo; Kokkaliaris, Konstantinos D.; Coutu, Daniel L.; Manz, Markus G.; Martin, Ivan and Schroeder, Timm (2019) In iScience 19. p.504-513
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... (More)

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

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biological Sciences, Stem Cells Research, Tissue Engineering
in
iScience
volume
19
pages
10 pages
publisher
Elsevier Inc.
external identifiers
  • scopus:85070937182
DOI
10.1016/j.isci.2019.08.006
language
English
LU publication?
yes
id
f43e271b-44b5-4d08-9b1a-5a7bb91025f2
date added to LUP
2019-09-09 14:09:47
date last changed
2019-09-26 04:41:54
@article{f43e271b-44b5-4d08-9b1a-5a7bb91025f2,
  abstract     = {<p>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</p>},
  author       = {Bourgine, Paul E. and Fritsch, Kristin and Pigeot, Sebastien and Takizawa, Hitoshi and Kunz, Leo and Kokkaliaris, Konstantinos D. and Coutu, Daniel L. and Manz, Markus G. and Martin, Ivan and Schroeder, Timm},
  keyword      = {Biological Sciences,Stem Cells Research,Tissue Engineering},
  language     = {eng},
  month        = {09},
  pages        = {504--513},
  publisher    = {Elsevier Inc.},
  series       = {iScience},
  title        = {Fate Distribution and Regulatory Role of Human Mesenchymal Stromal Cells in Engineered Hematopoietic Bone Organs},
  url          = {http://dx.doi.org/10.1016/j.isci.2019.08.006},
  volume       = {19},
  year         = {2019},
}