Tags

Type your tag names separated by a space and hit enter

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.

Authors+Show Affiliations

Departments of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA.Departments of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA.Departments of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA.Departments of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA. Departments of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA. Comprehensive Stroke Center, Illinois Neurological Institute, OSF HealthCare System, Saint Francis Medical Center, Peoria, Illinois, USA.Departments of Pathology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA.Departments of Neurology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA. Comprehensive Stroke Center, Illinois Neurological Institute, OSF HealthCare System, Saint Francis Medical Center, Peoria, Illinois, USA.Departments of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA. Departments of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA. Departments of Neurology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA.

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 -