Induction of Mesoderm and Neural Crest-Derived Pericytes from Human Pluripotent Stem Cells to Study Blood-Brain

Tannaz Faal1, Duc T T Phan2, Hayk Davtyan3

  • 1Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine CA 92697, USA; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine CA 92697, USA.

Stem Cell Reports
|February 13, 2019
PubMed

Insights

Researchers generated brain pericyte-like cells from patient stem cells to study Alzheimer's disease (AD). These cells could help understand blood-brain barrier (BBB) dysfunction in AD progression.

Area of Science:

  • Neuroscience
  • Stem Cell Biology
  • Vascular Biology

Background:

  • Pericytes are crucial for blood-brain barrier (BBB) integrity in the central nervous system (CNS).
  • BBB dysfunction is linked to Alzheimer's disease (AD) progression, but the specific role of pericytes remains unclear.
  • CNS pericytes originate from mesodermal and neural crest precursors during development.

Purpose of the Study:

  • To develop protocols for generating brain-specific pericyte-like cells from induced pluripotent stem cells (iPSCs).
  • To investigate the potential of these iPSC-derived pericytes in modeling BBB dysfunction in Alzheimer's disease.
  • To compare cells derived from healthy individuals and AD patients.

Main Methods:

  • Utilized induced pluripotent stem cell (iPSC) lines from healthy and AD patients.
  • Developed two distinct protocols employing mesodermal and neural crest intermediates.
  • Generated brain-specific pericyte-like cells from iPSCs.

Main Results:

  • Successfully generated iPSC-derived pericytes exhibiting stable expression of key surface markers and brain-specific genes.
  • Demonstrated functional capacity of these cells in promoting vascular tube formation.
  • Showcased the ability of iPSC-derived pericytes to enhance endothelial barrier properties.

Conclusions:

  • Established protocols for generating functional brain pericyte-like cells from patient-derived iPSCs.
  • These iPSC-derived pericytes serve as a valuable tool for studying the blood-brain barrier in Alzheimer's disease.
  • The findings offer new avenues for understanding pericyte involvement in AD-related BBB dysfunction.

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