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

被引：13

作者：

Bourgine, Paul E. ^{[1
,2
,3
,7
,8
]}

Fritsch, Kristin ^{[4
,5
]}

Pigeot, Sebastien ^{[2
,3
]}

Takizawa, Hitoshi ^{[6
]}

Kunz, Leo ^{[1
]}

Kokkaliaris, Konstantinos D. ^{[1
]}

Coutu, Daniel L. ^{[1
]}

Manz, Markus G. ^{[2
,3
]}

Martin, Ivan ^{[2
,3
]}

Schroeder, Timm ^{[1
]}

机构：

[1] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn D BSSE, Mattenstr 26, CH-4058 Basel, Switzerland

[2] Univ Basel, Dept Biomed, Tissue Engn, CH-4056 Basel, Switzerland

[3] Univ Hosp Basel, CH-4056 Basel, Switzerland

[4] Univ Hosp Zurich, Dept Hematol, CH-8091 Zurich, Switzerland

[5] Univ Zurich, CH-8091 Zurich, Switzerland

[6] Kumamoto Univ, Int Res Ctr Med Sci, Kumamoto 8600811, Japan

[7] Lund Univ, Dept Clin Sci, Lund Stem Cell Ctr, BMC B11, S-22184 Lund, Sweden

[8] Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden

来源：

ISCIENCE | 2019年 / 19卷

基金：

瑞士国家科学基金会;

关键词：

MARROW NICHE; CHEMOKINE SDF-1-ALPHA; MODEL ENABLES; MICE; MIGRATION; SDF-1; PROTEOGLYCANS; PROGENITORS; ENGRAFTMENT; EXPRESSION;

D O I：

10.1016/j.isci.2019.08.006

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：504 / +

页数：33

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