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

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Fate Distribution and Regulatory Role of Human Mesenchymal Stromal Cells in Engineered Hematopoietic Bone Organs. / Bourgine, Paul E.; Fritsch, Kristin; Pigeot, Sebastien; Takizawa, Hitoshi; Kunz, Leo; Kokkaliaris, Konstantinos D.; Coutu, Daniel L.; Manz, Markus G.; Martin, Ivan; Schroeder, Timm.

In: iScience, Vol. 19, 27.09.2019, p. 504-513.

Research output: Contribution to journalArticle

Harvard

Bourgine, PE, Fritsch, K, Pigeot, S, Takizawa, H, Kunz, L, Kokkaliaris, KD, Coutu, DL, Manz, MG, Martin, I & Schroeder, T 2019, 'Fate Distribution and Regulatory Role of Human Mesenchymal Stromal Cells in Engineered Hematopoietic Bone Organs', iScience, vol. 19, pp. 504-513. https://doi.org/10.1016/j.isci.2019.08.006

APA

CBE

Bourgine PE, Fritsch K, Pigeot S, Takizawa H, Kunz L, Kokkaliaris KD, Coutu DL, Manz MG, Martin I, Schroeder T. 2019. Fate Distribution and Regulatory Role of Human Mesenchymal Stromal Cells in Engineered Hematopoietic Bone Organs. iScience. 19:504-513. https://doi.org/10.1016/j.isci.2019.08.006

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Bourgine, Paul E. ; Fritsch, Kristin ; Pigeot, Sebastien ; Takizawa, Hitoshi ; Kunz, Leo ; Kokkaliaris, Konstantinos D. ; Coutu, Daniel L. ; Manz, Markus G. ; Martin, Ivan ; Schroeder, Timm. / Fate Distribution and Regulatory Role of Human Mesenchymal Stromal Cells in Engineered Hematopoietic Bone Organs. In: iScience. 2019 ; Vol. 19. pp. 504-513.

RIS

TY - JOUR

T1 - Fate Distribution and Regulatory Role of Human Mesenchymal Stromal Cells in Engineered Hematopoietic Bone Organs

AU - Bourgine, Paul E.

AU - Fritsch, Kristin

AU - Pigeot, Sebastien

AU - Takizawa, Hitoshi

AU - Kunz, Leo

AU - Kokkaliaris, Konstantinos D.

AU - Coutu, Daniel L.

AU - Manz, Markus G.

AU - Martin, Ivan

AU - Schroeder, Timm

PY - 2019/9/27

Y1 - 2019/9/27

N2 - 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

AB - 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

KW - Biological Sciences

KW - Stem Cells Research

KW - Tissue Engineering

U2 - 10.1016/j.isci.2019.08.006

DO - 10.1016/j.isci.2019.08.006

M3 - Article

VL - 19

SP - 504

EP - 513

JO - iScience

T2 - iScience

JF - iScience

SN - 2589-0042

ER -