Rapid and effective preparation of clonal bone marrow-derived mesenchymal stem/stromal cell sheets to reduce renal fibrosis
Abstract Allogeneic “off-the-shelf” mesenchymal stem/stromal cell (MSC) therapy requires scalable, quality-controlled cell manufacturing and distribution systems to provide clinical-grade products using cryogenic cell banking. However, previous studies report impaired cell function associated with a...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-31437-7 |
| _version_ | 1797864783533309952 |
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| author | Sumako Kameishi Celia M. Dunn Masatoshi Oka Kyungsook Kim Yun-Kyoung Cho Sun U. Song David W. Grainger Teruo Okano |
| author_facet | Sumako Kameishi Celia M. Dunn Masatoshi Oka Kyungsook Kim Yun-Kyoung Cho Sun U. Song David W. Grainger Teruo Okano |
| author_sort | Sumako Kameishi |
| collection | DOAJ |
| description | Abstract Allogeneic “off-the-shelf” mesenchymal stem/stromal cell (MSC) therapy requires scalable, quality-controlled cell manufacturing and distribution systems to provide clinical-grade products using cryogenic cell banking. However, previous studies report impaired cell function associated with administering freeze-thawed MSCs as single cell suspensions, potentially compromising reliable therapeutic efficacy. Using long-term culture-adapted clinical-grade clonal human bone marrow MSCs (cBMSCs) in this study, we engineered cBMSC sheets in 24 h to provide rapid preparation. We then sought to determine the influence of cBMSC freeze-thawing on both in vitro production of pro-regenerative factors and in vivo ability to reduce renal fibrosis in a rat model compared to freshly harvested cBMSCs. Sheets from freeze-thawed cBMSCs sheets exhibited comparable in vitro protein production and gene expression of pro-regenerative factors [e.g., hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and interleukin 10 (IL-10)] to freshly harvested cBMSC sheets. Additionally, freeze-thawed cBMSC sheets successfully suppressed renal fibrosis in vivo in an established rat ischemia–reperfusion injury model. Despite previous studies reporting that freeze-thawed MSCs exhibit impaired cell functions compared to fresh MSC single cell suspensions, cell sheets engineered from freeze-thawed cBMSCs do not exhibit impaired cell functions, supporting critical steps toward future clinical translation of cBMSC-based kidney disease treatment. |
| first_indexed | 2024-04-09T22:57:51Z |
| format | Article |
| id | doaj.art-e91a99820aa44a069683ec20c6c93603 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T22:57:51Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e91a99820aa44a069683ec20c6c936032023-03-22T11:10:46ZengNature PortfolioScientific Reports2045-23222023-03-0113111310.1038/s41598-023-31437-7Rapid and effective preparation of clonal bone marrow-derived mesenchymal stem/stromal cell sheets to reduce renal fibrosisSumako Kameishi0Celia M. Dunn1Masatoshi Oka2Kyungsook Kim3Yun-Kyoung Cho4Sun U. Song5David W. Grainger6Teruo Okano7Cell Sheet Tissue Engineering Center (CSTEC), University of UtahCell Sheet Tissue Engineering Center (CSTEC), University of UtahCell Sheet Tissue Engineering Center (CSTEC), University of UtahCell Sheet Tissue Engineering Center (CSTEC), University of UtahSCM Lifescience Co., Ltd.SCM Lifescience Co., Ltd.Cell Sheet Tissue Engineering Center (CSTEC), University of UtahCell Sheet Tissue Engineering Center (CSTEC), University of UtahAbstract Allogeneic “off-the-shelf” mesenchymal stem/stromal cell (MSC) therapy requires scalable, quality-controlled cell manufacturing and distribution systems to provide clinical-grade products using cryogenic cell banking. However, previous studies report impaired cell function associated with administering freeze-thawed MSCs as single cell suspensions, potentially compromising reliable therapeutic efficacy. Using long-term culture-adapted clinical-grade clonal human bone marrow MSCs (cBMSCs) in this study, we engineered cBMSC sheets in 24 h to provide rapid preparation. We then sought to determine the influence of cBMSC freeze-thawing on both in vitro production of pro-regenerative factors and in vivo ability to reduce renal fibrosis in a rat model compared to freshly harvested cBMSCs. Sheets from freeze-thawed cBMSCs sheets exhibited comparable in vitro protein production and gene expression of pro-regenerative factors [e.g., hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and interleukin 10 (IL-10)] to freshly harvested cBMSC sheets. Additionally, freeze-thawed cBMSC sheets successfully suppressed renal fibrosis in vivo in an established rat ischemia–reperfusion injury model. Despite previous studies reporting that freeze-thawed MSCs exhibit impaired cell functions compared to fresh MSC single cell suspensions, cell sheets engineered from freeze-thawed cBMSCs do not exhibit impaired cell functions, supporting critical steps toward future clinical translation of cBMSC-based kidney disease treatment.https://doi.org/10.1038/s41598-023-31437-7 |
| spellingShingle | Sumako Kameishi Celia M. Dunn Masatoshi Oka Kyungsook Kim Yun-Kyoung Cho Sun U. Song David W. Grainger Teruo Okano Rapid and effective preparation of clonal bone marrow-derived mesenchymal stem/stromal cell sheets to reduce renal fibrosis Scientific Reports |
| title | Rapid and effective preparation of clonal bone marrow-derived mesenchymal stem/stromal cell sheets to reduce renal fibrosis |
| title_full | Rapid and effective preparation of clonal bone marrow-derived mesenchymal stem/stromal cell sheets to reduce renal fibrosis |
| title_fullStr | Rapid and effective preparation of clonal bone marrow-derived mesenchymal stem/stromal cell sheets to reduce renal fibrosis |
| title_full_unstemmed | Rapid and effective preparation of clonal bone marrow-derived mesenchymal stem/stromal cell sheets to reduce renal fibrosis |
| title_short | Rapid and effective preparation of clonal bone marrow-derived mesenchymal stem/stromal cell sheets to reduce renal fibrosis |
| title_sort | rapid and effective preparation of clonal bone marrow derived mesenchymal stem stromal cell sheets to reduce renal fibrosis |
| url | https://doi.org/10.1038/s41598-023-31437-7 |
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