Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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.
Epigenetic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hematopoietic niche formation.
Blood. 2015; 125(2):249-260
Doi: 10.1182/blood-2014-04-572255
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- Führende Autor*innen der Med Uni Graz
- Reinisch Andreas
- Strunk Dirk
- Co-Autor*innen der Med Uni Graz
- Beham-Schmid Christine
- Hofmann Nicole
- Schallmoser Katharina
- Trajanoski Slave
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- Abstract:
- 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. © 2015 by The American Society of Hematology.
- Find related publications in this database (using NLM MeSH Indexing)
- Blotting, Western -
- Bone Marrow Cells - cytology
- Cell Differentiation - physiology
- Cell Lineage -
- Chondrogenesis - physiology
- Epigenesis, Genetic -
- Flow Cytometry -
- Hematopoietic Stem Cells - cytology
- Humans -
- Mesenchymal Stromal Cells - cytology
- Osteogenesis - physiology
- Stem Cell Niche -