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Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model
Akihiko Taguchi, … , Hiroaki Naritomi, Tomohiro Matsuyama
Akihiko Taguchi, … , Hiroaki Naritomi, Tomohiro Matsuyama
Published August 1, 2004
Citation Information: J Clin Invest. 2004;114(3):330-338. https://doi.org/10.1172/JCI20622.
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Article Cardiology

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model

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Abstract

Thrombo-occlusive cerebrovascular disease resulting in stroke and permanent neuronal loss is an important cause of morbidity and mortality. Because of the unique properties of cerebral vasculature and the limited reparative capability of neuronal tissue, it has been difficult to devise effective neuroprotective therapies in cerebral ischemia. Our results demonstrate that systemic administration of human cord blood–derived CD34+ cells to immunocompromised mice subjected to stroke 48 hours earlier induces neovascularization in the ischemic zone and provides a favorable environment for neuronal regeneration. Endogenous neurogenesis, suppressed by an antiangiogenic agent, is accelerated as a result of enhanced migration of neuronal progenitor cells to the damaged area, followed by their maturation and functional recovery. Our data suggest an essential role for CD34+ cells in promoting directly or indirectly an environment conducive to neovascularization of ischemic brain so that neuronal regeneration can proceed.

Authors

Akihiko Taguchi, Toshihiro Soma, Hidekazu Tanaka, Takayoshi Kanda, Hiroyuki Nishimura, Hiroo Yoshikawa, Yoshitane Tsukamoto, Hiroyuki Iso, Yoshihiro Fujimori, David M. Stern, Hiroaki Naritomi, Tomohiro Matsuyama

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Figure 2

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Transplantation of CD34+ cells after stroke accelerates neovascularizati...
Transplantation of CD34+ cells after stroke accelerates neovascularization. (A–D) Mice subjected to stroke received CD34+ cells (A and B), CD34– cells (C), or PBS alone (D) on day 2. Animals were infused with carbon black ink and killed at 24 hours after cell transplantations. Sections were stained with TTC. Neovascularization was noted at the border zone between the ACA and MCA areas (arrowheads show microvessels), especially in animals treated with CD34+ cells compared with those receiving CD34– cells or PBS alone. (E) An angiographic score for each experimental condition based on analysis of 6 mice per group. (F–H) Activated endothelial cells were observed with antibody specific for mouse CD13 in the ACA area. F: CD34+ cells; G: CD34– cells; H: PBS. (I) CBF was measured in the MCA area just outside of the penumbra, and values in animals treated with CD34+ cells (black bars), CD34– cells (gray bars), or PBS (white bars) were compared with values before cell transplantation at times corresponding to days 1, 7, and 14 after cell transplantation (n = 6 per group). Data shown are relative CBF versus day the measurement was performed. (J and K) Labeling vasculature by infusion of carbon black ink demonstrated neovasculature at the border of the MCA and ACA cortex in animals treated with CD34+ cells (J) and CD34+/Flk-1– cells (K) on day 7 after cell transplantation. Scale bars: 0.5 mm (A) and 0.1 mm (B, F, and J). *P < 0.05 versus PBS.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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