Angiogenic properties of human placenta-derived adherent cells and efficacy in hindlimb ischemia

J Vasc Surg. 2016 Sep;64(3):746-756.e1. doi: 10.1016/j.jvs.2015.04.387. Epub 2015 Jun 6.


Objective: Human placenta-derived adherent cells (PDACs) are a culture-expanded, undifferentiated mesenchymal-like population from full-term placental tissue and were previously shown to possess anti-inflammatory and immunomodulatory properties. PDACs (formulated as PDA-002) are in clinical trials for peripheral arterial disease with diabetic foot ulcer. In the current study, we examined their angiogenic and tissue reparative properties.

Methods: The effects of PDACs on survival and tube formation of human umbilical vein endothelial cells (HUVECs) were tested using conditioned media and noncontact coculture. Angiogenic effects were assessed in the chick chorioallantoic membrane assay. Hindlimb ischemia (HLI) was induced in mice and rats by femoral artery transection, and blood flow and blood vessel density were monitored in vivo by laser Doppler and angiography in the ischemic and control limbs. Tissue damage and regeneration in HLI were examined in histologic sections of quadriceps muscle stained with hematoxylin and eosin, and newly synthesized blood vessels were detected by indoxyl-tetrazolium staining for alkaline phosphatase.

Results: PDACs enhanced the survival of serum-starved HUVECs and stimulated HUVEC tube formation, and in the chick chorioallantoic membrane assay, PDACs stimulated blood vessel formation. In HLI, intramuscular administration of PDACs resulted in improved blood flow and vascular density, and in quadriceps muscle, tissue regeneration and increased numbers of blood vessels were observed.

Conclusions: PDACs exhibited various activities consistent with angiogenesis and tissue repair, supporting the continued investigation of this cell therapy as treatment for vascular disease-related indications.

Trial registration: NCT01859117.

MeSH terms

  • Animals
  • Blood Flow Velocity
  • Cell Adhesion*
  • Cells, Cultured
  • Chick Embryo
  • Chorioallantoic Membrane / blood supply*
  • Coculture Techniques
  • Culture Media, Conditioned / metabolism
  • Disease Models, Animal
  • Female
  • Hindlimb
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Ischemia / metabolism
  • Ischemia / physiopathology
  • Ischemia / surgery*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / physiology*
  • Mice, Inbred BALB C
  • Neovascularization, Physiologic*
  • Paracrine Communication
  • Placenta / cytology*
  • Pregnancy
  • Quadriceps Muscle / blood supply*
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Regional Blood Flow
  • Time Factors


  • Culture Media, Conditioned

Associated data