Reduced Ischemic Brain Injury by Partial Rejuvenation of Bone Marrow Cells in Aged Rats

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  • Akihiko Taguchi
    Department of Regenerative Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
  • Pengxiang Zhu
    Department of Functional Histology, Ehime University Graduate School of Medicine, Shitukawa, Toon, Ehime, Japan
  • Fang Cao
    Department of Functional Histology, Ehime University Graduate School of Medicine, Shitukawa, Toon, Ehime, Japan
  • Akie Kikuchi-Taura
    Department of Regenerative Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
  • Yukiko Kasahara
    Department of Regenerative Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
  • David M Stern
    VPHA and Dean's Office, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA
  • Toshihiro Soma
    Department of Hematology, Hyogo College of Medicine, Nshinomiya, Hyogo, Japan
  • Tomohiro Matsuyama
    Laboratory of Neurogenesis and CNS Repair, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nshinomiya, Hyogo, Japan
  • Ryuji Hata
    Department of Functional Histology, Ehime University Graduate School of Medicine, Shitukawa, Toon, Ehime, Japan

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<jats:p> Circulating bone marrow-derived immature cells, including endothelial progenitor cells, have been implicated in homeostasis of the microvasculature. Decreased levels of circulating endothelial progenitor cells, associated with aging and/or cardiovascular risk factors, correlate with poor clinical outcomes in a range of cardiovascular diseases. Herein, we transplanted bone marrow cells from young stroke-prone spontaneously hypertensive rats (SHR-SP) into aged SHR-SP, the latter not exposed to radiation or chemotherapy. Analysis of recipient peripheral blood 28 days after transplantation revealed that 5% of circulating blood cells were of donor origin. Cerebral infarction was induced on day 30 posttransplantation. Animals transplanted with bone marrow from young SHR-SP displayed an increase in density of the microvasculature in the periinfarction zone, reduced ischemic brain damage and improved neurologic function. In vitro analysis revealed enhanced activation of endothelial nitric oxide synthase and reduced activation p38 microtubule-associated protein (MAP) kinase, the latter associated with endothelial apoptosis, in cultures exposed to bone marrow-derived mononuclear cells from young animals versus cells from aged counterparts. Our findings indicate that partial rejuvenation of bone marrow from aged rats with cells from young animals enhances the response to ischemic injury, potentially at the level of endothelial/vascular activation, providing insight into a novel approach ameliorate chronic vascular diseases. </jats:p>

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