Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stress
Abstract Articular cartilage has limited healing capacity and no drugs are available that can prevent or slow the development of osteoarthritis (OA) after joint injury. Mesenchymal stromal cell (MSC)-based regenerative therapies for OA are increasingly common, but questions regarding their mechanism...
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Nature Portfolio
2022-12-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-022-25844-5 |
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author | Megan Fahey Maureen Bennett Matthew Thomas Kaylee Montney Irene Vivancos-Koopman Brenna Pugliese Lindsay Browning Lawrence J. Bonassar Michelle Delco |
author_facet | Megan Fahey Maureen Bennett Matthew Thomas Kaylee Montney Irene Vivancos-Koopman Brenna Pugliese Lindsay Browning Lawrence J. Bonassar Michelle Delco |
author_sort | Megan Fahey |
collection | DOAJ |
description | Abstract Articular cartilage has limited healing capacity and no drugs are available that can prevent or slow the development of osteoarthritis (OA) after joint injury. Mesenchymal stromal cell (MSC)-based regenerative therapies for OA are increasingly common, but questions regarding their mechanisms of action remain. Our group recently reported that although cartilage is avascular and relatively metabolically quiescent, injury induces chondrocyte mitochondrial dysfunction, driving cartilage degradation and OA. MSCs are known to rescue injured cells and improve healing by donating healthy mitochondria in highly metabolic tissues, but mitochondrial transfer has not been investigated in cartilage. Here, we demonstrate that MSCs transfer mitochondria to stressed chondrocytes in cell culture and in injured cartilage tissue. Conditions known to induce chondrocyte mitochondrial dysfunction, including stimulation with rotenone/antimycin and hyperoxia, increased transfer. MSC-chondrocyte mitochondrial transfer was blocked by non-specific and specific (connexin-43) gap-junction inhibition. When exposed to mechanically injured cartilage, MSCs localized to areas of matrix damage and extended cellular processes deep into microcracks, delivering mitochondria to chondrocytes. This work provides insights into the chemical, environmental, and mechanical conditions that can elicit MSC-chondrocyte mitochondrial transfer in vitro and in situ, and our findings suggest a new potential role for MSC-based therapeutics after cartilage injury. |
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institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-04-11T05:50:34Z |
publishDate | 2022-12-01 |
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spelling | doaj.art-f7286555ccfe44ef8e002eceae7875bd2022-12-22T04:42:05ZengNature PortfolioScientific Reports2045-23222022-12-0112111310.1038/s41598-022-25844-5Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stressMegan Fahey0Maureen Bennett1Matthew Thomas2Kaylee Montney3Irene Vivancos-Koopman4Brenna Pugliese5Lindsay Browning6Lawrence J. Bonassar7Michelle Delco8Department of Clinical Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Clinical Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Clinical Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Clinical Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Clinical Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Clinical Sciences, College of Veterinary Medicine, Cornell UniversityMeinig School of Biomedical Engineering, Sibley School of Mechanical and Aerospace Engineering, Cornell UniversityMeinig School of Biomedical Engineering, Sibley School of Mechanical and Aerospace Engineering, Cornell UniversityDepartment of Clinical Sciences, College of Veterinary Medicine, Cornell UniversityAbstract Articular cartilage has limited healing capacity and no drugs are available that can prevent or slow the development of osteoarthritis (OA) after joint injury. Mesenchymal stromal cell (MSC)-based regenerative therapies for OA are increasingly common, but questions regarding their mechanisms of action remain. Our group recently reported that although cartilage is avascular and relatively metabolically quiescent, injury induces chondrocyte mitochondrial dysfunction, driving cartilage degradation and OA. MSCs are known to rescue injured cells and improve healing by donating healthy mitochondria in highly metabolic tissues, but mitochondrial transfer has not been investigated in cartilage. Here, we demonstrate that MSCs transfer mitochondria to stressed chondrocytes in cell culture and in injured cartilage tissue. Conditions known to induce chondrocyte mitochondrial dysfunction, including stimulation with rotenone/antimycin and hyperoxia, increased transfer. MSC-chondrocyte mitochondrial transfer was blocked by non-specific and specific (connexin-43) gap-junction inhibition. When exposed to mechanically injured cartilage, MSCs localized to areas of matrix damage and extended cellular processes deep into microcracks, delivering mitochondria to chondrocytes. This work provides insights into the chemical, environmental, and mechanical conditions that can elicit MSC-chondrocyte mitochondrial transfer in vitro and in situ, and our findings suggest a new potential role for MSC-based therapeutics after cartilage injury.https://doi.org/10.1038/s41598-022-25844-5 |
spellingShingle | Megan Fahey Maureen Bennett Matthew Thomas Kaylee Montney Irene Vivancos-Koopman Brenna Pugliese Lindsay Browning Lawrence J. Bonassar Michelle Delco Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stress Scientific Reports |
title | Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stress |
title_full | Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stress |
title_fullStr | Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stress |
title_full_unstemmed | Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stress |
title_short | Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stress |
title_sort | mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial environmental and mechanical stress |
url | https://doi.org/10.1038/s41598-022-25844-5 |
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