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

Han Soo Kim, Seong Mi Choi, Wonsuk Yang, Dae-Sung Kim, Dongjin R. Lee, Sung Rae Cho, Dong Wook Kim

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)761-771
Number of pages11
JournalStem Cell Reviews and Reports
Volume10
Issue number6
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Fingerprint

Neural Cell Adhesion Molecules
Stroke
Brain
Mesenchymal Stromal Cells
Cell- and Tissue-Based Therapy
Neuroglia
Phosphates
Angiopoietin-1
polysialic acid
Human Embryonic Stem Cells
Middle Cerebral Artery Infarction
Transplantation
Survival

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research

Cite this

PSA-NCAM+ Neural Precursor Cells from Human Embryonic Stem Cells Promote Neural Tissue Integrity and Behavioral Performance in A Rat Stroke Model. / Kim, Han Soo; Choi, Seong Mi; Yang, Wonsuk; Kim, Dae-Sung; Lee, Dongjin R.; Cho, Sung Rae; Kim, Dong Wook.

In: Stem Cell Reviews and Reports, Vol. 10, No. 6, 01.01.2014, p. 761-771.

Research output: Contribution to journalArticle

Kim, Han Soo ; Choi, Seong Mi ; Yang, Wonsuk ; Kim, Dae-Sung ; Lee, Dongjin R. ; Cho, Sung Rae ; Kim, Dong Wook. / PSA-NCAM+ Neural Precursor Cells from Human Embryonic Stem Cells Promote Neural Tissue Integrity and Behavioral Performance in A Rat Stroke Model. In: Stem Cell Reviews and Reports. 2014 ; Vol. 10, No. 6. pp. 761-771.
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AU - Kim, Dong Wook

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AB - 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.

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