Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy
Nitric oxide (NO), as a gaseous therapeutic agent, shows great potential for the treatment of many kinds of diseases. Although various NO delivery systems have emerged, the immunogenicity and long-term toxicity of artificial carriers hinder the potential clinical translation of these gas therapeutic...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/84820 |
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| author | Haoyan Huang Meng Qian Yue Liu Shang Chen Huifang Li Zhibo Han Zhong-Chao Han Xiang-Mei Chen Qiang Zhao Zongjin Li |
| author_facet | Haoyan Huang Meng Qian Yue Liu Shang Chen Huifang Li Zhibo Han Zhong-Chao Han Xiang-Mei Chen Qiang Zhao Zongjin Li |
| author_sort | Haoyan Huang |
| collection | DOAJ |
| description | Nitric oxide (NO), as a gaseous therapeutic agent, shows great potential for the treatment of many kinds of diseases. Although various NO delivery systems have emerged, the immunogenicity and long-term toxicity of artificial carriers hinder the potential clinical translation of these gas therapeutics. Mesenchymal stem cells (MSCs), with the capacities of self-renewal, differentiation, and low immunogenicity, have been used as living carriers. However, MSCs as gaseous signaling molecule (GSM) carriers have not been reported. In this study, human MSCs were genetically modified to produce mutant β-galactosidase (β-GALH363A). Furthermore, a new NO prodrug, 6-methyl-galactose-benzyl-oxy NONOate (MGP), was designed. MGP can enter cells and selectively trigger NO release from genetically engineered MSCs (eMSCs) in the presence of β-GALH363A. Moreover, our results revealed that eMSCs can release NO when MGP is systemically administered in a mouse model of acute kidney injury (AKI), which can achieve NO release in a precise spatiotemporal manner and augment the therapeutic efficiency of MSCs. This eMSC and NO prodrug system provides a unique and tunable platform for GSM delivery and holds promise for regenerative therapy by enhancing the therapeutic efficiency of stem cells. |
| first_indexed | 2024-03-11T21:04:38Z |
| format | Article |
| id | doaj.art-7252d3fe7ee54915842cf2d763854d1a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-11T21:04:38Z |
| publishDate | 2023-09-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-7252d3fe7ee54915842cf2d763854d1a2023-09-29T14:58:43ZengeLife Sciences Publications LtdeLife2050-084X2023-09-011210.7554/eLife.84820Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapyHaoyan Huang0https://orcid.org/0000-0001-7753-7242Meng Qian1Yue Liu2Shang Chen3Huifang Li4Zhibo Han5Zhong-Chao Han6Xiang-Mei Chen7Qiang Zhao8Zongjin Li9https://orcid.org/0000-0002-4603-3743Nankai University School of Medicine, Tianjin, China; The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, the College of Life Sciences, Tianjin, China; National Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, ChinaThe Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, the College of Life Sciences, Tianjin, ChinaNankai University School of Medicine, Tianjin, ChinaNankai University School of Medicine, Tianjin, ChinaNankai University School of Medicine, Tianjin, ChinaJiangxi Engineering Research Center for Stem Cell, Shangrao, Jiangxi, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center of Cell Products, AmCellGene Co., Ltd, Tianjin, ChinaJiangxi Engineering Research Center for Stem Cell, Shangrao, Jiangxi, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center of Cell Products, AmCellGene Co., Ltd, Tianjin, China; Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co, Beijing, ChinaNational Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, ChinaThe Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, the College of Life Sciences, Tianjin, ChinaNankai University School of Medicine, Tianjin, China; The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, the College of Life Sciences, Tianjin, China; National Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, China; Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin, ChinaNitric oxide (NO), as a gaseous therapeutic agent, shows great potential for the treatment of many kinds of diseases. Although various NO delivery systems have emerged, the immunogenicity and long-term toxicity of artificial carriers hinder the potential clinical translation of these gas therapeutics. Mesenchymal stem cells (MSCs), with the capacities of self-renewal, differentiation, and low immunogenicity, have been used as living carriers. However, MSCs as gaseous signaling molecule (GSM) carriers have not been reported. In this study, human MSCs were genetically modified to produce mutant β-galactosidase (β-GALH363A). Furthermore, a new NO prodrug, 6-methyl-galactose-benzyl-oxy NONOate (MGP), was designed. MGP can enter cells and selectively trigger NO release from genetically engineered MSCs (eMSCs) in the presence of β-GALH363A. Moreover, our results revealed that eMSCs can release NO when MGP is systemically administered in a mouse model of acute kidney injury (AKI), which can achieve NO release in a precise spatiotemporal manner and augment the therapeutic efficiency of MSCs. This eMSC and NO prodrug system provides a unique and tunable platform for GSM delivery and holds promise for regenerative therapy by enhancing the therapeutic efficiency of stem cells.https://elifesciences.org/articles/84820nitric oxidegaseous signaling molecule genetically engineered mesenchymal stem cellacute kidney injurycontrolled releasedelivery |
| spellingShingle | Haoyan Huang Meng Qian Yue Liu Shang Chen Huifang Li Zhibo Han Zhong-Chao Han Xiang-Mei Chen Qiang Zhao Zongjin Li Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy eLife nitric oxide gaseous signaling molecule genetically engineered mesenchymal stem cell acute kidney injury controlled release delivery |
| title | Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy |
| title_full | Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy |
| title_fullStr | Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy |
| title_full_unstemmed | Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy |
| title_short | Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy |
| title_sort | genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy |
| topic | nitric oxide gaseous signaling molecule genetically engineered mesenchymal stem cell acute kidney injury controlled release delivery |
| url | https://elifesciences.org/articles/84820 |
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