Functional integration of human neural precursor cells in mouse cortex

Fu Wen Zhou, Jeff M. Fortin, Huan Xin Chen, Hildabelis Martinez-Diaz, Lung Ji Chang, Brent A. Reynolds, Steven N. Roper

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

This study investigates the electrophysiological properties and functional integration of different phenotypes of transplanted human neural precursor cells (hNPCs) in immunodeficient NSG mice. Postnatal day 2 mice received unilateral injections of 100,000 GFP+ hNPCs into the right parietal cortex. Eight weeks after transplantation, 1.21%of transplanted hNPCs survived. In these hNPCs, parvalbumin (PV)-, calretinin (CR)-, somatostatin (SS)-positive inhibitory interneurons and excitatory pyramidal neurons were confirmed electrophysiologically and histologically. All GFP+ hNPCs were immunoreactive with antihuman specific nuclear protein. The proportions of PV-, CR-, and SS-positive cells among GFP+ cells were 35.5%, 15.7%, and 17.1%, respectively; around 15% of GFP+ cells were identified as pyramidal neurons. Those electrophysiologically and histological identified GFP+ hNPCs were shown to fire action potentials with the appropriate firing patterns for different classes of neurons and to display spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs). The amplitude, frequency and kinetic properties of sEPSCs and sIPSCs in different types of hNPCs were comparable to host cells of the same type. In conclusion, GFP+ hNPCs produce neurons that are competent to integrate functionally into host neocortical neuronal networks. This provides promising data on the potential for hNPCs to serve as therapeutic agents in neurological diseases with abnormal neuronal circuitry such as epilepsy.

Original languageEnglish (US)
Article numbere0120281
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 12 2015

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Neurons
cortex
Calbindin 2
Parvalbumins
mice
Somatostatin
cells
Nuclear Proteins
neurons
Fires
Pyramidal Cells
Cells
somatostatin
Kinetics
Inhibitory Postsynaptic Potentials
Parietal Lobe
Somatostatin-Secreting Cells
Excitatory Postsynaptic Potentials
epilepsy
Interneurons

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Zhou, F. W., Fortin, J. M., Chen, H. X., Martinez-Diaz, H., Chang, L. J., Reynolds, B. A., & Roper, S. N. (2015). Functional integration of human neural precursor cells in mouse cortex. PLoS One, 10(3), [e0120281]. https://doi.org/10.1371/journal.pone.0120281

Functional integration of human neural precursor cells in mouse cortex. / Zhou, Fu Wen; Fortin, Jeff M.; Chen, Huan Xin; Martinez-Diaz, Hildabelis; Chang, Lung Ji; Reynolds, Brent A.; Roper, Steven N.

In: PLoS One, Vol. 10, No. 3, e0120281, 12.03.2015.

Research output: Contribution to journalArticle

Zhou, FW, Fortin, JM, Chen, HX, Martinez-Diaz, H, Chang, LJ, Reynolds, BA & Roper, SN 2015, 'Functional integration of human neural precursor cells in mouse cortex', PLoS One, vol. 10, no. 3, e0120281. https://doi.org/10.1371/journal.pone.0120281
Zhou FW, Fortin JM, Chen HX, Martinez-Diaz H, Chang LJ, Reynolds BA et al. Functional integration of human neural precursor cells in mouse cortex. PLoS One. 2015 Mar 12;10(3). e0120281. https://doi.org/10.1371/journal.pone.0120281
Zhou, Fu Wen ; Fortin, Jeff M. ; Chen, Huan Xin ; Martinez-Diaz, Hildabelis ; Chang, Lung Ji ; Reynolds, Brent A. ; Roper, Steven N. / Functional integration of human neural precursor cells in mouse cortex. In: PLoS One. 2015 ; Vol. 10, No. 3.
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