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Human umbilical cord blood-derived mesenchymal stem cells improve functional recovery through thrombospondin1, pantraxin3, and vascular endothelial growth factor in the ischemic rat brain.
J Neurosci Res 2015; 93(12):1814-25JN

Abstract

Cell therapy is a potential therapeutic method for cerebral ischemia, which remains a serious problem. In the search for more effective therapeutic methods, many kinds of stem cells from various tissues have been developed and tested as candidate therapeutic agents. Among them, human umbilical cord blood (hUCB)-derived mesenchymal stem cells (MSCs) are widely used for cell therapy because of their genetic flexibility. To confirm that they are effective and understand how they affect ischemic neural cells, hUCB-MSCs were directly administered ipsilaterally into an ischemic zone induced by middle cerebral artery occlusion (MCAO). We found that the neurobehavioral performance of the hUCB-MSC group was significantly improved compared with that of the vehicle-injected control group. The infarct was also remarkably smaller in the hUCB-MSC group. Additionally, hUCB-MSC transplantation resulted in a greater number of newly generated cells and angiogenic and tissue repair factors and a lower number of inflammatory events in the penumbra zone. To determine why these events occurred, hUCB-MSCs were assayed under hypoxic and normoxic conditions in vitro. The results showed that hUCB-MSCs exhibit higher expression levels of thrombospondin1, pantraxin3, and vascular endothelial growth factor under hypoxic conditions than under normoxic conditions. These results were found to be correlated with our in vivo immunofluorescent staining results. On the basis of these findings, we suggest that hUCB-MSCs may have a beneficial effect on cerebral ischemia, especially through angiogenesis, neurogenesis, and anti-inflammatory effects, and thus could be used as a therapeutic agent to treat neurological disorders such as cerebral ischemia.

Authors+Show Affiliations

Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea. Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota.Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.Stem Cell & Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea.Biomedical Research Institute, Medipost Co., Ltd., Seoul, Korea.Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.Biomedical Research Institute, Medipost Co., Ltd., Seoul, Korea.Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26332684

Citation

Park, Hyung Woo, et al. "Human Umbilical Cord Blood-derived Mesenchymal Stem Cells Improve Functional Recovery Through Thrombospondin1, Pantraxin3, and Vascular Endothelial Growth Factor in the Ischemic Rat Brain." Journal of Neuroscience Research, vol. 93, no. 12, 2015, pp. 1814-25.
Park HW, Moon HE, Kim HS, et al. Human umbilical cord blood-derived mesenchymal stem cells improve functional recovery through thrombospondin1, pantraxin3, and vascular endothelial growth factor in the ischemic rat brain. J Neurosci Res. 2015;93(12):1814-25.
Park, H. W., Moon, H. E., Kim, H. S., Paek, S. L., Kim, Y., Chang, J. W., ... Paek, S. H. (2015). Human umbilical cord blood-derived mesenchymal stem cells improve functional recovery through thrombospondin1, pantraxin3, and vascular endothelial growth factor in the ischemic rat brain. Journal of Neuroscience Research, 93(12), pp. 1814-25. doi:10.1002/jnr.23616.
Park HW, et al. Human Umbilical Cord Blood-derived Mesenchymal Stem Cells Improve Functional Recovery Through Thrombospondin1, Pantraxin3, and Vascular Endothelial Growth Factor in the Ischemic Rat Brain. J Neurosci Res. 2015;93(12):1814-25. PubMed PMID: 26332684.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human umbilical cord blood-derived mesenchymal stem cells improve functional recovery through thrombospondin1, pantraxin3, and vascular endothelial growth factor in the ischemic rat brain. AU - Park,Hyung Woo, AU - Moon,Hyo-Eun, AU - Kim,Hye-Soo R, AU - Paek,Seung Leal, AU - Kim,Yona, AU - Chang,Jong Wook, AU - Yang,Yoon Sun, AU - Kim,KwanWoo, AU - Oh,Wonil, AU - Hwang,Jae Ha, AU - Kim,Jin Wook, AU - Kim,Dong Gyu, AU - Paek,Sun Ha, Y1 - 2015/09/02/ PY - 2014/12/30/received PY - 2015/06/16/revised PY - 2015/06/17/accepted PY - 2015/9/3/entrez PY - 2015/9/4/pubmed PY - 2016/7/28/medline KW - angiogenesis KW - cytokine KW - human umbilical cord blood mesenchymal stem cell KW - ischemia KW - neurogenesis SP - 1814 EP - 25 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 93 IS - 12 N2 - Cell therapy is a potential therapeutic method for cerebral ischemia, which remains a serious problem. In the search for more effective therapeutic methods, many kinds of stem cells from various tissues have been developed and tested as candidate therapeutic agents. Among them, human umbilical cord blood (hUCB)-derived mesenchymal stem cells (MSCs) are widely used for cell therapy because of their genetic flexibility. To confirm that they are effective and understand how they affect ischemic neural cells, hUCB-MSCs were directly administered ipsilaterally into an ischemic zone induced by middle cerebral artery occlusion (MCAO). We found that the neurobehavioral performance of the hUCB-MSC group was significantly improved compared with that of the vehicle-injected control group. The infarct was also remarkably smaller in the hUCB-MSC group. Additionally, hUCB-MSC transplantation resulted in a greater number of newly generated cells and angiogenic and tissue repair factors and a lower number of inflammatory events in the penumbra zone. To determine why these events occurred, hUCB-MSCs were assayed under hypoxic and normoxic conditions in vitro. The results showed that hUCB-MSCs exhibit higher expression levels of thrombospondin1, pantraxin3, and vascular endothelial growth factor under hypoxic conditions than under normoxic conditions. These results were found to be correlated with our in vivo immunofluorescent staining results. On the basis of these findings, we suggest that hUCB-MSCs may have a beneficial effect on cerebral ischemia, especially through angiogenesis, neurogenesis, and anti-inflammatory effects, and thus could be used as a therapeutic agent to treat neurological disorders such as cerebral ischemia. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/26332684/Human_umbilical_cord_blood_derived_mesenchymal_stem_cells_improve_functional_recovery_through_thrombospondin1_pantraxin3_and_vascular_endothelial_growth_factor_in_the_ischemic_rat_brain_ L2 - https://doi.org/10.1002/jnr.23616 DB - PRIME DP - Unbound Medicine ER -