Intranasal delivery of stem cells as therapy for central nervous system disease
被引:59
作者:
Li, Yan-hua
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机构:
Shanxi Datong Univ, Inst Brain Sci, Sch Med, Dept Neurol, Datong 037009, Peoples R ChinaShanxi Datong Univ, Inst Brain Sci, Sch Med, Dept Neurol, Datong 037009, Peoples R China
Li, Yan-hua
[1
]
Feng, Ling
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机构:
Shanxi Datong Univ, Inst Brain Sci, Sch Med, Dept Neurol, Datong 037009, Peoples R ChinaShanxi Datong Univ, Inst Brain Sci, Sch Med, Dept Neurol, Datong 037009, Peoples R China
Feng, Ling
[1
]
Zhang, Guang-Xian
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机构:
Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USAShanxi Datong Univ, Inst Brain Sci, Sch Med, Dept Neurol, Datong 037009, Peoples R China
Zhang, Guang-Xian
[3
]
Ma, Cun-gen
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机构:
Shanxi Datong Univ, Inst Brain Sci, Sch Med, Dept Neurol, Datong 037009, Peoples R China
Shanxi Univ Tradit Chinese Med, Dept Encephalopathy, Collaborat Innovat Ctr 2011, Natl Major Clin Dept,Minist Hlth, Taiyuan 030024, Peoples R ChinaShanxi Datong Univ, Inst Brain Sci, Sch Med, Dept Neurol, Datong 037009, Peoples R China
Ma, Cun-gen
[1
,2
]
机构:
[1] Shanxi Datong Univ, Inst Brain Sci, Sch Med, Dept Neurol, Datong 037009, Peoples R China
[2] Shanxi Univ Tradit Chinese Med, Dept Encephalopathy, Collaborat Innovat Ctr 2011, Natl Major Clin Dept,Minist Hlth, Taiyuan 030024, Peoples R China
[3] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA
Stem cells, upon entering the CNS, can preferentially migrate into disease foci, where they exert therapeutic effects that compensate for lost tissue, reconstructing damaged neuronal circuitry and establishing in the brain a new microenvironment suitable for cell survival. However, the route of stem cell delivery into the CNS remains a challenge: with systemic administration (e.g., intravenous injection), a fraction of cells may be trapped in other organs than the CNS, while direct CNS injections, e.g., intracerebroventricular or transcranial, are invasive. Intranasal (i.n.) delivery of stem cells, in contrast, can effectively bypass the blood-brain barrier, rapidly enter the CNS, and minimize systemic distribution. I.n. delivery of stem cells may therefore be a safe and non-invasive way of targeting the CNS and would thus be a promising therapeutic option for CNS disease. In this review we discuss the i.n. route for stem cell delivery into the CNS, and the perspectives of i.n. stem cell-based therapy in CNS disease. (C) 2015 Elsevier Inc All rights reserved.
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Div Neurosurg, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Aboody, Karen S.
;
Najbauer, Joseph
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机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Najbauer, Joseph
;
Metz, Marianne Z.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Metz, Marianne Z.
;
D'Apuzzo, Massimo
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
D'Apuzzo, Massimo
;
Gutova, Margarita
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Gutova, Margarita
;
Annala, Alexander J.
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机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Annala, Alexander J.
;
Synold, Timothy W.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Dept Clin & Mol Pharmacol, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Synold, Timothy W.
;
Couture, Larry A.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Ctr Appl Technol Dev, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Couture, Larry A.
;
Blanchard, Suzette
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Div Biostat, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Blanchard, Suzette
;
Moats, Rex A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ So Calif, Childrens Hosp Los Angeles, Keck Sch Med, Dept Radiol, Los Angeles, CA 90027 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Moats, Rex A.
;
Garcia, Elizabeth
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Garcia, Elizabeth
;
Aramburo, Soraya
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机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Aramburo, Soraya
;
Valenzuela, Valerie V.
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h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Valenzuela, Valerie V.
;
Frank, Richard T.
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h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Frank, Richard T.
;
Barish, Michael E.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Barish, Michael E.
;
Brown, Christine E.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Dept Canc Immunotherapeut & Tumor Immunol, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Brown, Christine E.
;
Kim, Seung U.
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h-index: 0
机构:
Univ British Columbia, Dept Med, Div Neurol, UBC Hosp, Vancouver, BC V6T 2B5, CanadaCity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Kim, Seung U.
;
Badie, Behnam
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Div Neurosurg, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Badie, Behnam
;
Portnow, Jana
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机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Dept Med Oncol & Expt Therapeut, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
机构:
Univ Milan, Fac Med, Dept Hlth Sci, Via A di Rudini 8, I-20142 Milan, ItalyUniv Milan, Fac Med, Dept Hlth Sci, Via A di Rudini 8, I-20142 Milan, Italy
Scesa, Giuseppe
;
Bottai, Daniele
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Univ Milan, Fac Med, Dept Hlth Sci, Via A di Rudini 8, I-20142 Milan, ItalyUniv Milan, Fac Med, Dept Hlth Sci, Via A di Rudini 8, I-20142 Milan, Italy
机构:
Wayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Boster, Aaron
;
Edon, Gilles
论文数: 0引用数: 0
h-index: 0
机构:
CHU Rennes, Clin Neurol, Rennes, FranceWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Edon, Gilles
;
Frohman, Elliott
论文数: 0引用数: 0
h-index: 0
机构:
Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Frohman, Elliott
;
Javed, Adii
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Neurol, Chicago, IL 60637 USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Javed, Adii
;
Stuve, Olaf
论文数: 0引用数: 0
h-index: 0
机构:
Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Stuve, Olaf
;
Tselis, Alexandros
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h-index: 0
机构:
Wayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Tselis, Alexandros
;
Weiner, Howard
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h-index: 0
机构:
Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Weiner, Howard
;
Weinstock-Guttman, Bianca
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Buffalo, Jacobs Neurol Inst, Buffalo, NY 14260 USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Weinstock-Guttman, Bianca
;
Khan, Omar
论文数: 0引用数: 0
h-index: 0
机构:
Wayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Div Neurosurg, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Aboody, Karen S.
;
Najbauer, Joseph
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Najbauer, Joseph
;
Metz, Marianne Z.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Metz, Marianne Z.
;
D'Apuzzo, Massimo
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
D'Apuzzo, Massimo
;
Gutova, Margarita
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Gutova, Margarita
;
Annala, Alexander J.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Annala, Alexander J.
;
Synold, Timothy W.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Dept Clin & Mol Pharmacol, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Synold, Timothy W.
;
Couture, Larry A.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Ctr Appl Technol Dev, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Couture, Larry A.
;
Blanchard, Suzette
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Div Biostat, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Blanchard, Suzette
;
Moats, Rex A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ So Calif, Childrens Hosp Los Angeles, Keck Sch Med, Dept Radiol, Los Angeles, CA 90027 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Moats, Rex A.
;
Garcia, Elizabeth
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Garcia, Elizabeth
;
Aramburo, Soraya
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Aramburo, Soraya
;
Valenzuela, Valerie V.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Valenzuela, Valerie V.
;
Frank, Richard T.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Frank, Richard T.
;
Barish, Michael E.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Barish, Michael E.
;
Brown, Christine E.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Dept Canc Immunotherapeut & Tumor Immunol, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Brown, Christine E.
;
Kim, Seung U.
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med, Div Neurol, UBC Hosp, Vancouver, BC V6T 2B5, CanadaCity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Kim, Seung U.
;
Badie, Behnam
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Div Neurosurg, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
Badie, Behnam
;
Portnow, Jana
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Dept Med Oncol & Expt Therapeut, Duarte, CA 91010 USACity Hope Natl Med Ctr, Dept Neurosci, Duarte, CA 91010 USA
机构:
Univ Milan, Fac Med, Dept Hlth Sci, Via A di Rudini 8, I-20142 Milan, ItalyUniv Milan, Fac Med, Dept Hlth Sci, Via A di Rudini 8, I-20142 Milan, Italy
Scesa, Giuseppe
;
Bottai, Daniele
论文数: 0引用数: 0
h-index: 0
机构:
Univ Milan, Fac Med, Dept Hlth Sci, Via A di Rudini 8, I-20142 Milan, ItalyUniv Milan, Fac Med, Dept Hlth Sci, Via A di Rudini 8, I-20142 Milan, Italy
机构:
Wayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Boster, Aaron
;
Edon, Gilles
论文数: 0引用数: 0
h-index: 0
机构:
CHU Rennes, Clin Neurol, Rennes, FranceWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Edon, Gilles
;
Frohman, Elliott
论文数: 0引用数: 0
h-index: 0
机构:
Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Frohman, Elliott
;
Javed, Adii
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Neurol, Chicago, IL 60637 USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Javed, Adii
;
Stuve, Olaf
论文数: 0引用数: 0
h-index: 0
机构:
Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Stuve, Olaf
;
Tselis, Alexandros
论文数: 0引用数: 0
h-index: 0
机构:
Wayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Tselis, Alexandros
;
Weiner, Howard
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Weiner, Howard
;
Weinstock-Guttman, Bianca
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Buffalo, Jacobs Neurol Inst, Buffalo, NY 14260 USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA
Weinstock-Guttman, Bianca
;
Khan, Omar
论文数: 0引用数: 0
h-index: 0
机构:
Wayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USAWayne State Univ, Sch Med, Detroit Med Ctr, Multiple Sclerosis Clin Res Ctr,Dept Neurol, Detroit, MI 48201 USA