학술논문
Epigenetic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hematopoietic niche formation.
Document Type
Academic Journal
Author
Reinisch A; Stem Cell Research Unit and Division of Hematology and Stem Cell Transplantation, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford University, Stanford, CA;; Etchart N; Stem Cell Research Unit and Division of Hematology and Stem Cell Transplantation, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz, Graz, Austria;; Thomas D; Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford University, Stanford, CA;; Hofmann NA; Stem Cell Research Unit and Division of Hematology and Stem Cell Transplantation, Department of Internal Medicine, Medical University of Graz, Graz, Austria;; Fruehwirth M; Stem Cell Research Unit and Division of Hematology and Stem Cell Transplantation, Department of Internal Medicine, Medical University of Graz, Graz, Austria;; Sinha S; Department of Computer Science, and.; Chan CK; Department of Surgery, Stanford School of Medicine, Stanford University, Stanford, CA;; Senarath-Yapa K; Department of Surgery, Stanford School of Medicine, Stanford University, Stanford, CA;; Seo EY; Department of Surgery, Stanford School of Medicine, Stanford University, Stanford, CA;; Wearda T; Department of Surgery, Stanford School of Medicine, Stanford University, Stanford, CA;; Hartwig UF; University Medical Center, Third Department of Medicine, Johannes Gutenberg-University, Mainz, Germany;; Beham-Schmid C; Institute of Pathology and.; Trajanoski S; Center for Medical Research, Medical University of Graz, Graz, Austria;; Lin Q; Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, Rheinisch-Westfälische Technische Hochschule Aachen University Medical School, Aachen, Germany;; Wagner W; Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, Rheinisch-Westfälische Technische Hochschule Aachen University Medical School, Aachen, Germany;; Dullin C; Department of Diagnostic and Interventional Radiology, University Medical Center, Goettingen, Germany;; Alves F; Department of Molecular Biology of Neuronal Signals, Max Planck Institute for Experimental Medicine, Goettingen, Germany; Department of Hematology and Oncology, University Medical Center Goettingen, Goettingen, Germany;; Andreeff M; Departments of Stem Cell Transplantation & Cellular Therapy, Molecular Hematology & Therapy, and Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;; Weissman IL; Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford University, Stanford, CA; Departments of Pathology and Developmental Biology, Stanford School of Medicine, Stanford University, Stanford, CA;; Longaker MT; Department of Surgery, Stanford School of Medicine, Stanford University, Stanford, CA;; Schallmoser K; Stem Cell Research Unit and Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz, Graz, Austria; Department of Blood Group Serology and Transfusion Medicine, Paracelsus Medical University, Salzburg, Austria;; Majeti R; Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford University, Stanford, CA; Department of Medicine, Division of Hematology, Stanford School of Medicine, Stanford University, Stanford, CA; and.; Strunk D; Stem Cell Research Unit and Division of Hematology and Stem Cell Transplantation, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Institute for Experimental and Clinical Cell Therapy, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE
Subject
Language
English
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.)
(© 2015 by The American Society of Hematology.)