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

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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CD34+ cell transplantation in 24-week-old animals. (A–C) On day 35 after...
CD34+ cell transplantation in 24-week-old animals. (A–C) On day 35 after cell transplantation, the brains were evaluated. Compared with poststroke mice treated with CD34– cells (A), animals transplanted with CD34+ cells (B) showed an increase in area occupied by the left cortex. Significant cortical regeneration was induced by CD34+ cells transplantation (C). (D and E) Compared with CD34– cell transplantation (D), increased evidence of activated vasculature was observed in animals receiving CD34+ cells (E), as detected with mouse specific anti-CD13 antibody. (F–H) Migration of NPCs (small NeuN+ nuclei migrating toward the cortex) was observed in poststroke mice treated with CD34– cells (F) and with CD34+ cells (G). However, a significant increase in migrating NPCs was induced by CD34+ cell transplantation (H). (I and J) A thin layer of migrating PSA-NCAM+ NPCs was observed at the ischemic edge of the cortex in animals treated with CD34– cells (I), compared with a much thicker layer in those receiving CD34+ cells (J). Scale bars: 2 mm (A), 0.1 mm (D and I), and 0.4 mm (F). n = 4 in each group; *P < 0.05 versus CD34– cells.