Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases
Background/Aims: Stem cell treatment is one of the potential treatment options for ischemic stroke. We recently demonstrated a protective effect of human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) in a rat model of ischemic stroke. The treatment attenuated apoptosis and prevente...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2017-11-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/485533 |
| _version_ | 1811277202812043264 |
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| author | Bharath Chelluboina Koteswara Rao Nalamolu Gustavo G. Mendez Jeffrey D. Klopfenstein David M Pinson David Z Wang Krishna Kumar Veeravalli |
| author_facet | Bharath Chelluboina Koteswara Rao Nalamolu Gustavo G. Mendez Jeffrey D. Klopfenstein David M Pinson David Z Wang Krishna Kumar Veeravalli |
| author_sort | Bharath Chelluboina |
| collection | DOAJ |
| description | Background/Aims: Stem cell treatment is one of the potential treatment options for ischemic stroke. We recently demonstrated a protective effect of human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) in a rat model of ischemic stroke. The treatment attenuated apoptosis and prevented DNA damage. A collection of published studies, including several from our laboratory, indicated the induction and detrimental role for several matrix metalloproteinases (MMPs) in post-stroke brain injury. We hypothesized that the HUCB-MSCs treatment after focal cerebral ischemia prevents the dysregulation of MMPs and induces the expression of endogenous tissue inhibitors of metalloproteinases (TIMPs) to neutralize the elevated activity of MMPs. Methods: To test our hypothesis, we administered HUCB-MSCs (0.25 million cells/animal and 1 million cells/animal) intravenously via tail vein to male Sprague-Dawley rats that were subjected to a transient (two-hour) right middle cerebral artery occlusion (MCAO) and one-day reperfusion. Ischemic brain tissues obtained from various groups of rats seven days after reperfusion were subjected to real-time PCR, immunoblot, and immunofluorescence analysis. Results: HUCB-MSCs treatment prevented the induction of MMPs, which were upregulated in ischemia-induced rats that received no treatment. HUCB-MSCs treatment also prevented the induction of TIMPs expression. The extent of prevention of MMPs and TIMPs induction by HUCB-MSCs treatment is similar at both the doses tested. Conclusion: Prevention of stroke-induced MMPs upregulation after HUCB-MSCs treatment is not mediated through TIMPs upregulation. |
| first_indexed | 2024-04-13T00:12:38Z |
| format | Article |
| id | doaj.art-80c34aa392184e2d9c752d08a80d3852 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-13T00:12:38Z |
| publishDate | 2017-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-80c34aa392184e2d9c752d08a80d38522022-12-22T03:11:03ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-11-014441360136910.1159/000485533485533Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of MetalloproteinasesBharath ChelluboinaKoteswara Rao NalamoluGustavo G. MendezJeffrey D. KlopfensteinDavid M PinsonDavid Z WangKrishna Kumar VeeravalliBackground/Aims: Stem cell treatment is one of the potential treatment options for ischemic stroke. We recently demonstrated a protective effect of human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) in a rat model of ischemic stroke. The treatment attenuated apoptosis and prevented DNA damage. A collection of published studies, including several from our laboratory, indicated the induction and detrimental role for several matrix metalloproteinases (MMPs) in post-stroke brain injury. We hypothesized that the HUCB-MSCs treatment after focal cerebral ischemia prevents the dysregulation of MMPs and induces the expression of endogenous tissue inhibitors of metalloproteinases (TIMPs) to neutralize the elevated activity of MMPs. Methods: To test our hypothesis, we administered HUCB-MSCs (0.25 million cells/animal and 1 million cells/animal) intravenously via tail vein to male Sprague-Dawley rats that were subjected to a transient (two-hour) right middle cerebral artery occlusion (MCAO) and one-day reperfusion. Ischemic brain tissues obtained from various groups of rats seven days after reperfusion were subjected to real-time PCR, immunoblot, and immunofluorescence analysis. Results: HUCB-MSCs treatment prevented the induction of MMPs, which were upregulated in ischemia-induced rats that received no treatment. HUCB-MSCs treatment also prevented the induction of TIMPs expression. The extent of prevention of MMPs and TIMPs induction by HUCB-MSCs treatment is similar at both the doses tested. Conclusion: Prevention of stroke-induced MMPs upregulation after HUCB-MSCs treatment is not mediated through TIMPs upregulation.https://www.karger.com/Article/FullText/485533Stem cellsIschemiaReperfusionMMPsTIMPsInduction |
| spellingShingle | Bharath Chelluboina Koteswara Rao Nalamolu Gustavo G. Mendez Jeffrey D. Klopfenstein David M Pinson David Z Wang Krishna Kumar Veeravalli Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Cellular Physiology and Biochemistry Stem cells Ischemia Reperfusion MMPs TIMPs Induction |
| title | Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases |
| title_full | Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases |
| title_fullStr | Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases |
| title_full_unstemmed | Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases |
| title_short | Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases |
| title_sort | mesenchymal stem cell treatment prevents post stroke dysregulation of matrix metalloproteinases and tissue inhibitors of metalloproteinases |
| topic | Stem cells Ischemia Reperfusion MMPs TIMPs Induction |
| url | https://www.karger.com/Article/FullText/485533 |
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