Transplanted Stem Cell-Secreted Vascular Endothelial Growth Factor Effects Poststroke Recovery, Inflammation, and Vascular Repair
Open accessAbstract
Cell transplantation offers a novel therapeutic strategy for stroke; however, how transplanted cells function in vivo is poorly understood. We show for the first time that after subacute transplantation into the ischemic brain of human central nervous system stem cells grown as neurospheres (hCNS-SCns), the stem cell-secreted factor, human vascular endothelial growth factor (hVEGF), is necessary for cell-induced functional recovery. We correlate this functional recovery to hVEGF-induced effects on the host brain including multiple facets of vascular repair and its unexpected suppression of the inflammatory response. We found that transplanted hCNS-SCns affected multiple parameters in the brain with different kinetics: early improvement in blood-brain barrier integrity and suppression of inflammation was followed by a delayed spatiotemporal regulated increase in neovascularization. These events coincided with a bimodal pattern of functional recovery, with, an early recovery independent of neovascularization, and a delayed hVEGF-dependent recovery coincident with neovascularization. Therefore, cell transplantation therapy offers an exciting multimodal strategy for brain repair in stroke and potentially other disorders with a vascular or inflammatory component.
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Transplantation of allogeneic mesenchymal stem cells and neural stem cells can stabilize BBB and promote BBB integrity in stroke models, in addition to neuroprotection.
“For example, transplantation of allogeneic mesenchymal stem cells and neural stem cells, in addition to offering neuroprotection, can stabilize BBB and promote BBB integrity as shown in stroke models (260, 463, 578).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [260]
The Results report reduced BBB leakage after human neural stem-cell transplantation in stroke-model rats, and the Discussion reports prior findings that neural stem cells or mesenchymal stem cells improve BBB integrity. However, the Methods describe human cells transplanted into rats, not allogeneic transplantation, and these passages do not establish neuroprotection by both cell types. (LLM, conf=0.86)
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- Authors
- Horie, N., Pereira, M. P., Niizuma, K., Sun, G., Keren-Gill, H., Encarnacion, A., Shamloo, M., Hamilton, S. A., Jiang, K., Huhn, S., Palmer, T. D., Bliss, T. M., & Steinberg, G. K.
- Affiliations
- Stanford Medicine (US)
- Department of Neurosurgery and Stanford Stroke Center, Stanford Institute for Neuro-Innovation and Translational Neurosciences, Stanford University School of Medicine, Stanford, California, USA
- StemCells (United States) (US)
- Corresponding author
- Bliss, Tonya M.
- Steinberg, Gary K.
- ORCID
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-02-01
- Volume
- 29
- Issue
- 2
- Pages
- 274-285
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- PMC
- PMC3524414
- OpenAlex
- W1999783884
- Cited by
- 240
- References
- 58
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 13 · 2022: 5 · 2021: 14 · 2020: 16 · 2019: 12 · 2018: 22 · 2017: 22 · 2016: 20 · 2015: 24 · 2014: 25 · 2013: 26 · 2012: 19
- FWCI
- 12.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Stem Cells (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health National Institute of Neurological Disorders and Stroke (NS058784, NS27292, NS37520)
- William Randolph Hearst Foundation, Bernard and Ronni Lacroute, Russell and Elizabeth Siegelman, and the Edward E. Hills Fund
- Ministry of Education and Science of Spain
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- stroke, cell transplantation, neurospheres, vascular endothelial growth factor, vascular repair, neovascularization, blood-brain barrier integrity, neuroinflammation, functional recovery, ischemic brain, brain repair
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Cell Differentiation, Cells, Cultured, Central Nervous System, Humans, Rats, Nude, Stem Cells, Wound Healing, Neovascularization, Physiologic, Recovery of Function, Stroke, Stem Cell Transplantation, Vascular Endothelial Growth Factors, Rats
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