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 language | English |
|---|---|
| Pages (from-to) | 761-771 |
| Number of pages | 11 |
| Journal | Stem Cell Reviews and Reports |
| Volume | 10 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2014 Jan 1 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - PSA-NCAM+ Neural Precursor Cells from Human Embryonic Stem Cells Promote Neural Tissue Integrity and Behavioral Performance in A Rat Stroke Model
AU - Kim, Han Soo
AU - Choi, Seong Mi
AU - Yang, Wonsuk
AU - Kim, Dae-Sung
AU - Lee, Dongjin R.
AU - Cho, Sung Rae
AU - Kim, Dong Wook
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
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.
KW - Human embryonic stem cells
KW - Ischemic stroke
KW - Mesenchymal stem cells
KW - Neural precursor cells
KW - Pluripotent stem cells
KW - PSA-NCAM
UR - http://www.scopus.com/inward/record.url?scp=84929279629&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929279629&partnerID=8YFLogxK
U2 - 10.1007/s12015-014-9535-y
DO - 10.1007/s12015-014-9535-y
M3 - Article
C2 - 24974101
AN - SCOPUS:84929279629
VL - 10
SP - 761
EP - 771
JO - Stem Cell Reviews
JF - Stem Cell Reviews
SN - 1550-8943
IS - 6
ER -