Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model
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
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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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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Therapeutic neovascularization, due to CD34+ cell transplantation after ...
Therapeutic neovascularization, due to CD34+ cell transplantation after stroke, enhances neurogenesis. (A–F) On day 14 after CD34– cell transplantation, mature cortical neurons were observed up to the edge of the ischemic region displaying neuronal markers, NeuN (A) and MAP-2 (B), whereas only a thin layer of migrating PSA-NCAM+ NPCs was observed at the ischemic edge (C). In contrast, after transplantation of CD34+ cells, expanded cortical areas displaying a low density of NeuN+ (D) and MAP-2+ cells (E) were observed beyond the boundary demarcating mature neurons. Migration of NPCs into this expanded area was also observed by PSA-NCAM staining (F). (G–I) On day 14, TUNEL+ cells were visualized around the lower part of the expanded cortical area. Whereas massive cell death was observed in animals receiving CD34– cell transplantation (G), the number of TUNEL+ profiles was strongly reduced in mice transplanted with CD34+ cells (H). (I) The average number of TUNEL+ cells per HPF. Three sections were evaluated in each animal; n = 5 per group. Arrowheads indicate the expanded cortical areas displaying a low density of indicated marker. Scale bars: 100 μm (A) and 50 μm (G). *P < 0.05 for CD34+ versus CD34– cell transplantation.