Brain pericytes derived from human pluripotent stem cells retain vascular and phagocytic functions under hypoxia.

Abstract

The integrity and function of the blood‑brain barrier (BBB) are largely regulated by pericytes. Pericyte deficiency leads to BBB breakdown and neurological dysfunction in major neurological disorders including stroke and Alzheimer's disease (AD). Transplantation of pericytes derived from induced pluripotent stem cells (iPSC‑PC) has been shown to restore the BBB and improve functional recovery in mouse models of stroke and pericyte deficiency. However, the molecular profile and functional properties of iPSC‑PC under hypoxic conditions, similar to those found in ischemic and neurodegenerative diseases remain largely unexplored. We examined iPSC‑PC under hypoxia to assess molecular marker expression, proliferation, ability to home to brain vessels, and uptake of amyloid beta (Aβ). iPSC‑PC under severe hypoxia retain essential functional properties, including key molecular markers, proliferation rates, and the ability to migrate to host brain vessels via function‑associated PDGFRB‑PDGF‑BB signaling. Additionally, we show that iPSC‑PC exhibit similar clearance of Aβ neurotoxins from AD mouse brain sections under both normoxic and hypoxic conditions. These findings suggest that iPSC‑PC functions are largely resilient to hypoxia, highlighting their potential as a promising cell source for treating ischemic and neurodegenerative disorders.