title: Fibroblast-Derived Extracellular Matrix Induces Chondrogenic Differentiation in Human Adipose-Derived Mesenchymal Stromal/Stem Cells in Vitro.
abstract: Mesenchymal stromal/stem cells (MSCs) represent an area being intensively researched for tissue engineering and regenerative medicine applications. MSCs may provide the opportunity to treat diseases and injuries that currently have limited therapeutic options, as well as enhance present strategies for tissue repair. The cellular environment has a significant role in cellular development and differentiation through cell-matrix interactions. The aim of this study was to investigate the behavior of adipose-derived MSCs (ad-MSCs) in the context of a cell-derived matrix so as to model the in vivo physiological microenvironment. The fibroblast-derived extracellular matrix (fd-ECM) did not affect ad-MSC morphology, but reduced ad-MSC proliferation. Ad-MSCs cultured on fd-ECM displayed decreased expression of integrins α2 and β1 and subsequently lost their multipotency over time, as shown by the decrease in CD44, Octamer-binding transcription factor 4 (OCT4), SOX2, and NANOG gene expression. The fd-ECM induced chondrogenic differentiation in ad-MSCs compared to control ad-MSCs. Loss of function studies, through the use of siRNA and a mutant Notch1 construct, revealed that ECM-mediated ad-MSCs chondrogenesis requires Notch1 and β-catenin signaling. The fd-ECM also showed anti-senescence effects on ad-MSCs. The fd-ECM is a promising approach for inducing chondrogenesis in ad-MSCs and chondrogenic differentiated ad-MSCs could be used in stem cell therapy procedures.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Anzio Road, Observatory, Cape Town 7925, South Africa. kd.dzobo@uct.ac.za.|Division of Medical Biochemistry, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa. kd.dzobo@uct.ac.za.
authors.forename: Kevin
authors.initials: K
authors.lastname: Dzobo
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Anzio Road, Observatory, Cape Town 7925, South Africa. taegyn.turnley@alumni.uct.ac.za.|Division of Medical Biochemistry, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa. taegyn.turnley@alumni.uct.ac.za.
authors.forename: Taegyn
authors.initials: T
authors.lastname: Turnley
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Anzio Road, Observatory, Cape Town 7925, South Africa. andrew.wishart@alumni.uct.ac.za.|Division of Medical Biochemistry, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa. andrew.wishart@alumni.uct.ac.za.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wishart
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Anzio Road, Observatory, Cape Town 7925, South Africa. arielle.rowe@icgeb.org.
authors.forename: Arielle
authors.initials: A
authors.lastname: Rowe
authors.affiliation: Department of Immunology, Institute for Cellular and Molecular Medicine, South African Medical Research Council (SAMRC) Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria 0002, South Africa. karlienkallmeyer@gmail.com.
authors.forename: Karlien
authors.initials: K
authors.lastname: Kallmeyer
authors.affiliation: Department of Immunology, Institute for Cellular and Molecular Medicine, South African Medical Research Council (SAMRC) Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria 0002, South Africa. fionavanvollenstee@gmail.com.
authors.forename: Fiona A
authors.initials: FA
authors.lastname: van Vollenstee
authors.affiliation: Division of Human Genetics, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa. thmnic023@myuct.ac.za.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Thomford
authors.affiliation: Division of Human Genetics, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa. collet.dandara@uct.ac.za.
authors.forename: Collet
authors.initials: C
authors.lastname: Dandara
authors.affiliation: Division of Immunology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa. denis.chopera@gmail.com.
authors.forename: Denis
authors.initials: D
authors.lastname: Chopera
authors.affiliation: Department of Immunology, Institute for Cellular and Molecular Medicine, South African Medical Research Council (SAMRC) Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria 0002, South Africa. michael.pepper@up.ac.za.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Pepper
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Anzio Road, Observatory, Cape Town 7925, South Africa. iqbal.parker@icgeb.org.|Division of Medical Biochemistry, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa. iqbal.parker@icgeb.org.
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Parker
mesh_terms: D052436:Adipose Tissue, White / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D016922:Cellular Senescence; D020219:Chondrogenesis; D005109:Extracellular Matrix / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*
keywords: chondrogenesis; differentiation; extracellular matrix; mesenchymal stromal/stem cells; regenerative medicine; three-dimensional