Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases.Cell Physiol Biochem 2017; 44(4):1360-1369CP
Abstract
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.
Links
MeSH
Pub Type(s)
Journal Article
Language
eng
PubMed ID
29186705
Citation
Chelluboina, Bharath, et al. "Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 44, no. 4, 2017, pp. 1360-1369.
Chelluboina B, Nalamolu KR, Mendez GG, et al. Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases. Cell Physiol Biochem. 2017;44(4):1360-1369.
Chelluboina, B., Nalamolu, K. R., Mendez, G. G., Klopfenstein, J. D., Pinson, D. M., Wang, D. Z., & Veeravalli, K. K. (2017). Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 44(4), pp. 1360-1369. doi:10.1159/000485533.
Chelluboina B, et al. Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases. Cell Physiol Biochem. 2017;44(4):1360-1369. PubMed PMID: 29186705.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR
T1 - Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases.
AU - Chelluboina,Bharath,
AU - Nalamolu,Koteswara Rao,
AU - Mendez,Gustavo G,
AU - Klopfenstein,Jeffrey D,
AU - Pinson,David M,
AU - Wang,David Z,
AU - Veeravalli,Krishna Kumar,
Y1 - 2017/11/30/
PY - 2017/08/22/received
PY - 2017/10/17/accepted
PY - 2017/12/1/pubmed
PY - 2018/1/19/medline
PY - 2017/11/30/entrez
KW - Induction
KW - Ischemia
KW - MMPs
KW - Reperfusion
KW - Stem cells
KW - TIMPs
SP - 1360
EP - 1369
JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
JO - Cell. Physiol. Biochem.
VL - 44
IS - 4
N2 - 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.
SN - 1421-9778
UR - https://www.unboundmedicine.com/medline/citation/29186705/Mesenchymal_Stem_Cell_Treatment_Prevents_Post_Stroke_Dysregulation_of_Matrix_Metalloproteinases_and_Tissue_Inhibitors_of_Metalloproteinases_
L2 - https://www.karger.com?DOI=10.1159/000485533
DB - PRIME
DP - Unbound Medicine
ER -
