Human umbilical cord blood-derived mesenchymal stem cells improve functional recovery through thrombospondin1, pantraxin3, and vascular endothelial growth factor in the ischemic rat brain.
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.
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.
Hyung Woo
HW
Park
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.
Hyo-Eun
HE
Moon
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.
Hye-Soo R
HS
Kim
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.
Seung Leal
SL
Paek
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.
Yona
Y
Kim
Stem Cell & Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea.
Jong Wook
JW
Chang
Biomedical Research Institute, Medipost Co., Ltd., Seoul, Korea.
Yoon Sun
YS
Yang
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.
KwanWoo
K
Kim
Biomedical Research Institute, Medipost Co., Ltd., Seoul, Korea.
Wonil
W
Oh
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.
Jae Ha
JH
Hwang
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.
Jin Wook
JW
Kim
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.
Dong Gyu
DG
Kim
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.
Sun Ha
SH
Paek
D000704:Analysis of Variance; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism*; D051928:CD47 Antigen / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D020127:Recovery of Function / Q000502:physiology*; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000099153:Pentraxins
D002097:C-Reactive Protein; D051928:CD47 Antigen; D009419:Nerve Tissue Proteins; D000683:Serum Amyloid P-Component; D042461:Vascular Endothelial Growth Factor A; D000099153:Pentraxins
angiogenesis; cytokine; human umbilical cord blood mesenchymal stem cell; ischemia; neurogenesis