Inability of Low Oxygen Tension to Induce Chondrogenesis in Human Infrapatellar Fat Pad Mesenchymal Stem Cells

ObjectiveArticular cartilage of the knee joint is avascular, exists under a low oxygen tension microenvironment, and does not self-heal when injured. Human infrapatellar fat pad-sourced mesenchymal stem cells (IFP-MSC) are an arthroscopically accessible source of mesenchymal stem cells (MSC) for the...

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Main Authors: Samia Rahman, Alexander R. A. Szojka, Yan Liang, Melanie Kunze, Victoria Goncalves, Aillette Mulet-Sierra, Nadr M. Jomha, Adetola B. Adesida
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2021.703038/full
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author Samia Rahman
Alexander R. A. Szojka
Yan Liang
Melanie Kunze
Victoria Goncalves
Aillette Mulet-Sierra
Nadr M. Jomha
Adetola B. Adesida
Adetola B. Adesida
author_facet Samia Rahman
Alexander R. A. Szojka
Yan Liang
Melanie Kunze
Victoria Goncalves
Aillette Mulet-Sierra
Nadr M. Jomha
Adetola B. Adesida
Adetola B. Adesida
author_sort Samia Rahman
collection DOAJ
description ObjectiveArticular cartilage of the knee joint is avascular, exists under a low oxygen tension microenvironment, and does not self-heal when injured. Human infrapatellar fat pad-sourced mesenchymal stem cells (IFP-MSC) are an arthroscopically accessible source of mesenchymal stem cells (MSC) for the repair of articular cartilage defects. Human IFP-MSC exists physiologically under a low oxygen tension (i.e., 1–5%) microenvironment. Human bone marrow mesenchymal stem cells (BM-MSC) exist physiologically within a similar range of oxygen tension. A low oxygen tension of 2% spontaneously induced chondrogenesis in micromass pellets of human BM-MSC. However, this is yet to be demonstrated in human IFP-MSC or other adipose tissue-sourced MSC. In this study, we explored the potential of low oxygen tension at 2% to drive the in vitro chondrogenesis of IFP-MSC. We hypothesized that 2% O2 will induce stable chondrogenesis in human IFP-MSC without the risk of undergoing endochondral ossification at ectopic sites of implantation.MethodsMicromass pellets of human IFP-MSC were cultured under 2% O2 or 21% O2 (normal atmosphere O2) in the presence or absence of chondrogenic medium with transforming growth factor-β3 (TGFβ3) for 3 weeks. Following in vitro chondrogenesis, the resulting pellets were implanted in immunodeficient athymic nude mice for 3 weeks.ResultsA low oxygen tension of 2% was unable to induce chondrogenesis in human IFP-MSC. In contrast, chondrogenic medium with TGFβ3 induced in vitro chondrogenesis. All pellets were devoid of any evidence of undergoing endochondral ossification after subcutaneous implantation in athymic mice.
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spelling doaj.art-f0e4a17213264b52b79ff98593272bce2022-12-21T22:07:23ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-07-01910.3389/fcell.2021.703038703038Inability of Low Oxygen Tension to Induce Chondrogenesis in Human Infrapatellar Fat Pad Mesenchymal Stem CellsSamia Rahman0Alexander R. A. Szojka1Yan Liang2Melanie Kunze3Victoria Goncalves4Aillette Mulet-Sierra5Nadr M. Jomha6Adetola B. Adesida7Adetola B. Adesida8Laboratory of Stem Cell Biology and Orthopedic Tissue Engineering, Division of Orthopedic Surgery and Surgical Research, Department of Surgery, University of Alberta, Edmonton, AB, CanadaLaboratory of Stem Cell Biology and Orthopedic Tissue Engineering, Division of Orthopedic Surgery and Surgical Research, Department of Surgery, University of Alberta, Edmonton, AB, CanadaLaboratory of Stem Cell Biology and Orthopedic Tissue Engineering, Division of Orthopedic Surgery and Surgical Research, Department of Surgery, University of Alberta, Edmonton, AB, CanadaLaboratory of Stem Cell Biology and Orthopedic Tissue Engineering, Division of Orthopedic Surgery and Surgical Research, Department of Surgery, University of Alberta, Edmonton, AB, CanadaLaboratory of Stem Cell Biology and Orthopedic Tissue Engineering, Division of Orthopedic Surgery and Surgical Research, Department of Surgery, University of Alberta, Edmonton, AB, CanadaLaboratory of Stem Cell Biology and Orthopedic Tissue Engineering, Division of Orthopedic Surgery and Surgical Research, Department of Surgery, University of Alberta, Edmonton, AB, CanadaLaboratory of Stem Cell Biology and Orthopedic Tissue Engineering, Division of Orthopedic Surgery and Surgical Research, Department of Surgery, University of Alberta, Edmonton, AB, CanadaLaboratory of Stem Cell Biology and Orthopedic Tissue Engineering, Division of Orthopedic Surgery and Surgical Research, Department of Surgery, University of Alberta, Edmonton, AB, CanadaDivision of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Alberta Hospital, Edmonton, AB, CanadaObjectiveArticular cartilage of the knee joint is avascular, exists under a low oxygen tension microenvironment, and does not self-heal when injured. Human infrapatellar fat pad-sourced mesenchymal stem cells (IFP-MSC) are an arthroscopically accessible source of mesenchymal stem cells (MSC) for the repair of articular cartilage defects. Human IFP-MSC exists physiologically under a low oxygen tension (i.e., 1–5%) microenvironment. Human bone marrow mesenchymal stem cells (BM-MSC) exist physiologically within a similar range of oxygen tension. A low oxygen tension of 2% spontaneously induced chondrogenesis in micromass pellets of human BM-MSC. However, this is yet to be demonstrated in human IFP-MSC or other adipose tissue-sourced MSC. In this study, we explored the potential of low oxygen tension at 2% to drive the in vitro chondrogenesis of IFP-MSC. We hypothesized that 2% O2 will induce stable chondrogenesis in human IFP-MSC without the risk of undergoing endochondral ossification at ectopic sites of implantation.MethodsMicromass pellets of human IFP-MSC were cultured under 2% O2 or 21% O2 (normal atmosphere O2) in the presence or absence of chondrogenic medium with transforming growth factor-β3 (TGFβ3) for 3 weeks. Following in vitro chondrogenesis, the resulting pellets were implanted in immunodeficient athymic nude mice for 3 weeks.ResultsA low oxygen tension of 2% was unable to induce chondrogenesis in human IFP-MSC. In contrast, chondrogenic medium with TGFβ3 induced in vitro chondrogenesis. All pellets were devoid of any evidence of undergoing endochondral ossification after subcutaneous implantation in athymic mice.https://www.frontiersin.org/articles/10.3389/fcell.2021.703038/fullchondrogenesisadipose tissuehuman mesenchymal stem cellsoxygen tensionxenograftin vivo calcification
spellingShingle Samia Rahman
Alexander R. A. Szojka
Yan Liang
Melanie Kunze
Victoria Goncalves
Aillette Mulet-Sierra
Nadr M. Jomha
Adetola B. Adesida
Adetola B. Adesida
Inability of Low Oxygen Tension to Induce Chondrogenesis in Human Infrapatellar Fat Pad Mesenchymal Stem Cells
Frontiers in Cell and Developmental Biology
chondrogenesis
adipose tissue
human mesenchymal stem cells
oxygen tension
xenograft
in vivo calcification
title Inability of Low Oxygen Tension to Induce Chondrogenesis in Human Infrapatellar Fat Pad Mesenchymal Stem Cells
title_full Inability of Low Oxygen Tension to Induce Chondrogenesis in Human Infrapatellar Fat Pad Mesenchymal Stem Cells
title_fullStr Inability of Low Oxygen Tension to Induce Chondrogenesis in Human Infrapatellar Fat Pad Mesenchymal Stem Cells
title_full_unstemmed Inability of Low Oxygen Tension to Induce Chondrogenesis in Human Infrapatellar Fat Pad Mesenchymal Stem Cells
title_short Inability of Low Oxygen Tension to Induce Chondrogenesis in Human Infrapatellar Fat Pad Mesenchymal Stem Cells
title_sort inability of low oxygen tension to induce chondrogenesis in human infrapatellar fat pad mesenchymal stem cells
topic chondrogenesis
adipose tissue
human mesenchymal stem cells
oxygen tension
xenograft
in vivo calcification
url https://www.frontiersin.org/articles/10.3389/fcell.2021.703038/full
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