Derivation of Pericytes from Human Pluripotent Stem Cells

Ayelet Dar1, Joseph Itskovitz-Eldor2

  • 1Orthopaedic Hospital Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. darayelet@gmail.com.

Insights

Human pluripotent stem cells (hPSCs) can generate pericytes, which are crucial for blood vessel formation. These hPSC-derived pericytes promote healing in ischemic tissues and can be efficiently produced using embryoid bodies.

Area of Science:

  • Stem cell biology
  • Regenerative medicine
  • Vascular biology

Background:

  • Human pluripotent stem cells (hPSCs) are a versatile source for generating various cell types.
  • Pericytes are multipotent vascular precursor cells essential for angiogenesis and tissue repair.
  • Current methods for pericyte generation require optimization for large-scale production.

Purpose of the Study:

  • To establish a protocol for the efficient derivation of large quantities of pericytes from hPSCs.
  • To characterize the vasculogenic and proliferative potential of hPSC-derived pericytes.
  • To evaluate the therapeutic efficacy of hPSC-pericytes in a preclinical model of ischemia.

Main Methods:

  • Spontaneous differentiation of hPSCs into embryoid bodies.
  • Isolation and culture of pericytes from differentiating embryoid bodies.
  • Assessment of pericyte markers, proliferation, and differentiation potential.
  • In vivo transplantation of hPSC-pericytes into a murine hind limb ischemia model.

Main Results:

  • A robust protocol was developed for generating numerous pericytes from hPSC-embryoid bodies.
  • hPSC-derived pericytes demonstrated sustained proliferation and vasculogenic properties.
  • Transplantation of hPSC-pericytes led to therapeutic angiogenesis and reduced muscle wasting in ischemic limbs.

Conclusions:

  • hPSC-derived pericytes represent a promising cell source for regenerative therapies targeting ischemic diseases.
  • The described protocol facilitates large-scale production of clinical-grade pericytes.
  • hPSC-pericytes hold significant potential for promoting tissue repair and vascularization.

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