Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats
Left ventricular hypertrophy (LVH) in hypertension has prognostic significance on cardiovascular mortality and morbidity. Recently, we have shown that n-butylidenephthalide (BP) improves human adipose-derived stem cell (hADSC) engraftment via attenuated reactive oxygen species (ROS) production. This...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-10-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231718312643 |
| _version_ | 1818203989573894144 |
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| author | Tsung-Ming Lee Horng-Jyh Harn Tzyy-Wen Chiou Ming-Hsi Chuang Chun-Hung Chen Chi-Hsuan Chuang Po-Cheng Lin Shinn-Zong Lin |
| author_facet | Tsung-Ming Lee Horng-Jyh Harn Tzyy-Wen Chiou Ming-Hsi Chuang Chun-Hung Chen Chi-Hsuan Chuang Po-Cheng Lin Shinn-Zong Lin |
| author_sort | Tsung-Ming Lee |
| collection | DOAJ |
| description | Left ventricular hypertrophy (LVH) in hypertension has prognostic significance on cardiovascular mortality and morbidity. Recently, we have shown that n-butylidenephthalide (BP) improves human adipose-derived stem cell (hADSC) engraftment via attenuated reactive oxygen species (ROS) production. This prompted us to investigate whether remote transplantation of BP-pretreated hADSCs confers attenuated LVH at an established phase of hypertension. Male spontaneously hypertensive rats (SHRs) aged 12 weeks were randomly allocated to receive right hamstring injection of vehicle, clinical-grade hADSCs, and BP-preconditioned hADSCs for 8 weeks. As compared with untreated SHRs, naïve hADSCs decreased the ratio of LV weight to tibia, cardiomyocyte cell size, and collagen deposition independent of hemodynamic changes. These changes were accompanied by attenuated myocardial ROS production and increased p-STAT3 levels. Compared with naïve hADSCs, BP-preconditioned hADSCs provided a further decrease of ROS and LVH and an increase of local hADSC engraftment, STAT3 phosphorylation, STAT3 activity, STAT3 nuclear translocation, myocardial IL-10 levels, and the percentage of M2 macrophage infiltration. SIN-1 or S3I-201 reversed the effects of BP-preconditioned ADSCs increase on myocardial IL-10 levels. Furthermore, SIN-1 abolished the phosphorylation of STAT3, whereas superoxide levels were not affected following the inhibition of STAT3. Our results highlighted the feasibility of remote transplantation of hADSCs can be considered as an alternative procedure to reverse cardiac hypertrophy even at an established phase of hypertension. BP-pretreated hADSCs polarize macrophages into M2 immunoregulatory cells more efficiently than naïve hADSCs via ROS/STAT3 pathway. Keywords: Adipose-derived stem cell, Butylidenephthalide, Left ventricular hypertrophy, M2 macrophage, Signal transducer and activator of transcription 3, Spontaneously hypertensive rats |
| first_indexed | 2024-12-12T03:34:06Z |
| format | Article |
| id | doaj.art-f26b412a8716460c952d9c8a21f7835b |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-12T03:34:06Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-f26b412a8716460c952d9c8a21f7835b2022-12-22T00:39:51ZengElsevierRedox Biology2213-23172019-10-0127Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive ratsTsung-Ming Lee0Horng-Jyh Harn1Tzyy-Wen Chiou2Ming-Hsi Chuang3Chun-Hung Chen4Chi-Hsuan Chuang5Po-Cheng Lin6Shinn-Zong Lin7Cardiovascular Institute, An Nan Hospital, China Medical University, Tainan, Taiwan; Department of Medicine, China Medical University, Taichung, TaiwanBioinnovation Center, Tzu Chi Foundation, Department of Pathology, Buddhist Tzu Chi General Hospital, Tzu Chi University, TaiwanDepartment of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, TaiwanDepartment of Technology Management, Chung Hua University, Hsinchu, Taiwan; Gwo Xi Stem Cell Applied Technology, Hsinchu, TaiwanGwo Xi Stem Cell Applied Technology, Hsinchu, TaiwanGenomics Research Center, Academia Sinica, Taipei, TaiwanGwo Xi Stem Cell Applied Technology, Hsinchu, TaiwanBioinnovation Center, Tzu Chi Foundation, Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Tzu Chi University, Taiwan; Corresponding author. Bioinnovation Center, Tzu Chi Foundation and Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Tzu Chi University, No.707, Sec. 3, Chung Yang Rd. 970, Hualien, Taiwan.Left ventricular hypertrophy (LVH) in hypertension has prognostic significance on cardiovascular mortality and morbidity. Recently, we have shown that n-butylidenephthalide (BP) improves human adipose-derived stem cell (hADSC) engraftment via attenuated reactive oxygen species (ROS) production. This prompted us to investigate whether remote transplantation of BP-pretreated hADSCs confers attenuated LVH at an established phase of hypertension. Male spontaneously hypertensive rats (SHRs) aged 12 weeks were randomly allocated to receive right hamstring injection of vehicle, clinical-grade hADSCs, and BP-preconditioned hADSCs for 8 weeks. As compared with untreated SHRs, naïve hADSCs decreased the ratio of LV weight to tibia, cardiomyocyte cell size, and collagen deposition independent of hemodynamic changes. These changes were accompanied by attenuated myocardial ROS production and increased p-STAT3 levels. Compared with naïve hADSCs, BP-preconditioned hADSCs provided a further decrease of ROS and LVH and an increase of local hADSC engraftment, STAT3 phosphorylation, STAT3 activity, STAT3 nuclear translocation, myocardial IL-10 levels, and the percentage of M2 macrophage infiltration. SIN-1 or S3I-201 reversed the effects of BP-preconditioned ADSCs increase on myocardial IL-10 levels. Furthermore, SIN-1 abolished the phosphorylation of STAT3, whereas superoxide levels were not affected following the inhibition of STAT3. Our results highlighted the feasibility of remote transplantation of hADSCs can be considered as an alternative procedure to reverse cardiac hypertrophy even at an established phase of hypertension. BP-pretreated hADSCs polarize macrophages into M2 immunoregulatory cells more efficiently than naïve hADSCs via ROS/STAT3 pathway. Keywords: Adipose-derived stem cell, Butylidenephthalide, Left ventricular hypertrophy, M2 macrophage, Signal transducer and activator of transcription 3, Spontaneously hypertensive ratshttp://www.sciencedirect.com/science/article/pii/S2213231718312643 |
| spellingShingle | Tsung-Ming Lee Horng-Jyh Harn Tzyy-Wen Chiou Ming-Hsi Chuang Chun-Hung Chen Chi-Hsuan Chuang Po-Cheng Lin Shinn-Zong Lin Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats Redox Biology |
| title | Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats |
| title_full | Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats |
| title_fullStr | Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats |
| title_full_unstemmed | Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats |
| title_short | Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats |
| title_sort | remote transplantation of human adipose derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats |
| url | http://www.sciencedirect.com/science/article/pii/S2213231718312643 |
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