Stem Cell Reviews and Reports

, Volume 10, Issue 6, pp 761–771 | Cite as

PSA-NCAM+ Neural Precursor Cells from Human Embryonic Stem Cells Promote Neural Tissue Integrity and Behavioral Performance in A Rat Stroke Model

Article
First Online:

Abstract

Recently, cell-based therapy has been highlighted as an alternative to treating ischemic brain damage in stroke patients. The present study addresses the therapeutic potential of polysialic acid-neural cell adhesion molecule (PSA-NCAM)-positive neural precursor cells (NPCPSA-NCAM+) derived from human embryonic stem cells (hESCs) in a rat stroke model with permanent middle cerebral artery occlusion. Data showed that rats transplanted with NPCPSA-NCAM+ are superior to those treated with phosphate buffered saline (PBS) or mesenchymal stem cells (MSCs) in behavioral performance throughout time points. In order to investigate its underlying events, immunohistochemical analysis was performed on rat ischemic brains treated with PBS, MSCs, and NPCPSA-NCAM+. Unlike MSCs, NPCPSA-NCAM+ demonstrated a potent immunoreactivity against human specific nuclei, doublecortin, and Tuj1 at day 26 post-transplantation, implying their survival, differentiation, and integration in the host brain. Significantly, NPCPSA-NCAM+ evidently lowered the positivity of microglial ED-1 and astrocytic GFAP, suggesting a suppression of adverse glial activation in the host brain. In addition, NPCPSA-NCAM+ elevated α-SMA+ immunoreactivity and the expression of angiopoietin-1 indicating angiogenic stimulation in the host brain. Taken together, the current data demonstrate that transplanted NPCPSA-NCAM+ preserve brain tissue with reduced infarct size and improve behavioral performance through actions encompassing anti-reactive glial activation and pro-angiogenic activity in a rat stroke model. In conclusion, the present findings support the potentiality of NPCPSA-NCAM+ as the promising source in the development of cell-based therapy for neurological diseases including ischemic stroke.

Keywords

PSA-NCAM Neural precursor cells Human embryonic stem cells Pluripotent stem cells Mesenchymal stem cells Ischemic stroke 
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Notes

Acknowledgments

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (2010-0020408; 2012M3A9B4028631; 2012M3A9B4028639; 2012M3A9C7050126), and by a grant (A1202254) of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea. Seong-Mi Choi and Wonsuk Yang equally contributed to this work.

Conflict of Interest

The authors declare no potential conflicts of interest in this study.

Supplementary material

12015_2014_9535_MOESM1_ESM.pptx (69 kb)
Fig. S1 The expression levels of rat and human neurotrophic factors in ischemic brain were assessed using RT-PCR at day 26 after transplantation with NPCPSA-NCAM+”, respectively, MSCs or PBS. A representative RT-PCR amplification of neurotrophic factors and the quantification of GAPDH-normalized mRNA levels to that of sham controls (baseline) (n = 3 per group) are shown. Values are mean ± S.E.M. *P < 0.05 when compared to those of PBS group.(PPTX 69.1kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Han-Soo Kim
    • 1
  • Seong-Mi Choi
    • 1
  • Wonsuk Yang
    • 1
  • Dae-Sung Kim
    • 1
  • Dongjin R. Lee
    • 1
    • 2
  • Sung-Rae Cho
    • 3
  • Dong-Wook Kim
    • 1
    • 2
  1. 1.Department of Physiology and Cell Therapy CenterYonsei University College of MedicineSeoulSouth Korea
  2. 2.Brain Korea 21 Plus Project for Medical ScienceYonsei University College of MedicineSeoulSouth Korea
  3. 3.Department and Research Institute of Rehabilitation MedicineYonsei University College of MedicineSeoulSouth Korea

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