Fate Distribution and Regulatory Role of Human Mesenchymal Stromal Cells in Engineered Hematopoietic Bone Organs
Paul E. Bourgine,
Kristin Fritsch,
Sebastien Pigeot,
Hitoshi Takizawa,
Leo Kunz,
Konstantinos D. Kokkaliaris,
Daniel L. Coutu,
Markus G. Manz,
Ivan Martin,
Timm Schroeder
Affiliations
Paul E. Bourgine
Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland; Tissue Engineering, Department of Biomedicine, University of Basel and University Hospital Basel, 4056 Basel, Switzerland; Department of Clinical Sciences, Lund Stem Cell Center, Lund University, BMC B11, 221 84 Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden
Kristin Fritsch
Department of Hematology, University Hospital Zurich and University of Zurich, 8091 Zurich, Switzerland
Sebastien Pigeot
Tissue Engineering, Department of Biomedicine, University of Basel and University Hospital Basel, 4056 Basel, Switzerland
Hitoshi Takizawa
International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
Leo Kunz
Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland
Konstantinos D. Kokkaliaris
Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland
Daniel L. Coutu
Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland
Markus G. Manz
Tissue Engineering, Department of Biomedicine, University of Basel and University Hospital Basel, 4056 Basel, Switzerland; Corresponding author
Ivan Martin
Tissue Engineering, Department of Biomedicine, University of Basel and University Hospital Basel, 4056 Basel, Switzerland; Corresponding author
Timm Schroeder
Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland; Corresponding author
Summary: 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 Subject Areas: Biological Sciences, Stem Cells Research, Tissue Engineering
