Identification of neuronal outgrowth cells from peripheral blood of stroke patients
Keun-Hwa Jung MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Division of Epidemic Intelligence Service, Korea Center for Disease Control and Prevention, Seoul National University Hospital, Seoul
K.-H.J. and K.C. contributed equally to this work.
Search for more papers by this authorKon Chu MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul
K.-H.J. and K.C. contributed equally to this work.
Search for more papers by this authorSoon-Tae Lee MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Search for more papers by this authorEun-Cheol Song MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Department of Neurology, Inha University Hospital, Incheon, South Korea
Search for more papers by this authorDong-In Sinn MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Search for more papers by this authorJeong-Min Kim MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Search for more papers by this authorSe-Jeong Kim MS
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Search for more papers by this authorJin-Hee Kim BS
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Search for more papers by this authorKyung-Muk Kang BS
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Search for more papers by this authorHee-Kwon Park MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Search for more papers by this authorSeung-Hoon Lee MD, PhD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Search for more papers by this authorManho Kim MD, PhD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Search for more papers by this authorSang Kun Lee MD, PhD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul
Search for more papers by this authorCorresponding Author
Jae-Kyu Roh MD, PhD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Department of Neurology, Seoul National University Hospital, 28, Yongon-dong, Chongro-gu, Seoul, 110-744, South KoreaSearch for more papers by this authorKeun-Hwa Jung MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Division of Epidemic Intelligence Service, Korea Center for Disease Control and Prevention, Seoul National University Hospital, Seoul
K.-H.J. and K.C. contributed equally to this work.
Search for more papers by this authorKon Chu MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul
K.-H.J. and K.C. contributed equally to this work.
Search for more papers by this authorSoon-Tae Lee MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Search for more papers by this authorEun-Cheol Song MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Department of Neurology, Inha University Hospital, Incheon, South Korea
Search for more papers by this authorDong-In Sinn MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Search for more papers by this authorJeong-Min Kim MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Search for more papers by this authorSe-Jeong Kim MS
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Search for more papers by this authorJin-Hee Kim BS
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Search for more papers by this authorKyung-Muk Kang BS
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Search for more papers by this authorHee-Kwon Park MD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Search for more papers by this authorSeung-Hoon Lee MD, PhD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Search for more papers by this authorManho Kim MD, PhD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Search for more papers by this authorSang Kun Lee MD, PhD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul
Search for more papers by this authorCorresponding Author
Jae-Kyu Roh MD, PhD
Department of Neurology, Stroke and Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Clinical Research Institute
Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Center, Seoul National University
Department of Neurology, Seoul National University Hospital, 28, Yongon-dong, Chongro-gu, Seoul, 110-744, South KoreaSearch for more papers by this authorAbstract
Objective
Recent studies have identified a subset of outgrowth cell population with endothelial phenotype in long-term cultures of peripheral blood mononuclear cells. The concept that peripheral blood–derived cells participate in neuronal regeneration remains highly controversial, and no specific cell type has been identified. In this study, we undertook to characterize outgrowth cells in the peripheral blood culture from stroke patients.
Methods
Mononuclear cells were isolated from the peripheral blood of 30 acute stroke patients, 20 risk factor–only subjects, and 20 healthy volunteers. The isolation frequency of outgrowth cells was measured during the 2 months of culture. The outgrowth cells were characterized by in vitro cultures and in vivo model of transplantation into the ischemic rat brain.
Results
Outgrowth cells could be more efficiently isolated from stroke patients (80%) than risk factor–only (30%) and healthy groups (10%). Outgrowth cells were more detected in the patients with greater National Institute of Health Stroke Scale scores (p = 0.023). They exhibited heterogenous populations with different morphologies, for example, cobblestone, palisading, or branching features. Two different types of outgrowth cells were identified: endothelial; neuronal, according to their morphological characteristics; and protein or gene expression profiles. The transplanted neuronal outgrowth cells survived in the ischemic rat brains over 6 months after transplantation. Targeted migration of the transplanted cells was seen in the ischemic brains with phenotypes of neuronal phenotypes.
Interpretation
The feasibility of extracting and culturing neuronal outgrowth cells in large numbers suggests that such autologous cells will be useful for applications ranging from basic research to cell-based therapy. Ann Neurol 2008
Supporting Information
This article includes supplementary materials available via the Internet at http://www.interscience.wiley.com/jpages/0364-5134/suppmat
| Filename | Description |
|---|---|
| ana21303-ANA21303supp_F1.tif2.7 MB | Figure 1. Differentiation profiles of transplanted DiO-labeled, lysed cells. Confocal scans depict the distribution of various phenotypic markers (red) after the transplantation of freeze-thaw-DiO-labeled, lysed cells (green) within the needle tract (A), and lesional (B) and non-lesional brain regions (C) at 35 days after MCA occlusion. The localization of NF (D), GFAP (E) and laminin (F), and DiO after the infusion of lysed cells mirrored the pattern observed after the transplantation of live cells. Arrows denote DiO-labeled host cells. Scale bar: 30 μm. |
| ana21303-ANA21303supp_F2.tif4.9 MB | Figure 2. Differentiation profiles of transplanted endothelial outgrowth cells. Fluorescent microscopy shows representative immunostainings of DiO-labeled endothelial outgrowth cells (green) for various phenotypic markers (red) at 35 days after MCA occlusion. Migrating, transplanted cells rarely expressed NeuN (A-C) or NF (D-F). Some DiO-labeled cells were colocalized with EBA (G-I), or laminin (J-L). Scale bar: 60 μμm. |
| ana21303-ANA21303Supplementary_Table1.doc38.5 KB | Supporting Information file ana21303-ANA21303Supplementary_Table1.doc |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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