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Forschungsdatenbank PMU-SQQUID

Epigenetic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hematopoietic niche formation.
Reinisch, A; Etchart, N; Thomas, D; Hofmann, NA; Fruehwirth, M; Sinha, S; Chan, CK; Senarath-Yapa, K; Seo, EY; Wearda, T; Hartwig, UF; Beham-Schmid, C; Trajanoski, S; Lin, Q; Wagner, W; Dullin, C; Alves, F; Andreeff, M; Weissman, IL; Longaker, MT; Schallmoser, K; Majeti, R; Strunk, D;
Blood. 2015; 125(2): 249-260.
Originalarbeiten (Zeitschrift)


Schallmoser Katharina
Strunk Dirk


In the last decade there has been a rapid expansion in clinical trials using mesenchymal stromal cells (MSCs) from a variety of tissues. However, despite similarities in morphology, immunophenotype, and differentiation behavior in vitro, MSCs sourced from distinct tissues do not necessarily have equivalent biological properties. We performed a genome-wide methylation, transcription, and in vivo evaluation of MSCs from human bone marrow (BM), white adipose tissue, umbilical cord, and skin cultured in humanized media. Surprisingly, only BM-derived MSCs spontaneously formed a BM cavity through a vascularized cartilage intermediate in vivo that was progressively replaced by hematopoietic tissue and bone. Only BM-derived MSCs exhibited a chondrogenic transcriptional program with hypomethylation and increased expression of RUNX3, RUNX2, BGLAP, MMP13, and ITGA10 consistent with a latent and primed skeletal developmental potential. The humanized MSC-derived microenvironment permitted homing and maintenance of long-term murine SLAM(+) hematopoietic stem cells (HSCs), as well as human CD34(+)/CD38(-)/CD90(+)/CD45RA(+) HSCs after cord blood transplantation. These studies underscore the profound differences in developmental potential between MSC sources independent of donor age, with implications for their clinical use. We also demonstrate a tractable human niche model for studying homing and engraftment of human hematopoietic cells in normal and neoplastic states.

Useful keywords (using NLM MeSH Indexing)

Blotting, Western

Bone Marrow Cells/cytology

Cell Differentiation/physiology

Cell Lineage*


Epigenesis, Genetic*

Flow Cytometry

Hematopoietic Stem Cells/cytology*


Mesenchymal Stromal Cells/cytology*


Stem Cell Niche*