title: The role of placental-derived adherent stromal cell (PLX-PAD) in the treatment of critical limb ischemia.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSC) are spindle-shaped plastic-adherent cells isolated from bone marrow (BM), adipose tissue and other organs, including the placenta. Autologous BM-derived MSC have been studied in animals with experimentally induced critical limb ischemia (CLI) as a model of end-stage peripheral vascular disease. While demonstrating therapeutic benefit, the use of these cells is limited by the need to surgically extract BM and the fear of thrombosis secondary to the use of granulocyte-colony-stimulating factor (G-CSF) to mobilize the cells.
  
  
  METHODS
  We studied the use of placental-derived adherent stromal cells (ASC) in a standard limb ischemia model of male Balb/c mice. These placental-derived cells, termed PLX-PAD, share the adherence and marker expression of BM-derived MSC but lack their differentiation potential. PLX-PAD are isolated from human placenta following a Caesarean section and cultured in a bioreactor, termed the PluriX System. The PluriX System provides a three-dimensional (3-D) microenvironment that enables the large-scale growth of these cells. PLX-PAD are stable adhesive cells that can be expanded in vitro without the loss of phenotype and without showing signs of karyotypic changes.
  
  
  RESULTS
  The intramuscular (i.m.) administration of PLX-PAD in our model significantly improved blood flow (BF) (P=0.0008), increased capillary density (P=0.021), reduced oxidative stress (P=0.034) and reduced endothelial damage (P=0.004), while increasing limb function versus the administration of a phosphate-buffered saline (PBS) control vehicle in the affected limb.
  
  
  CONCLUSIONS
  Allogeneic placental-derived ASC may provide an off-the-shelf supply of therapeutic cells that would need no histocompatible tissue matching and be potentially less expensive and considerably more convenient than BM or adipose-derived MSC.
authors.affiliation: Pluristem Therapeutics Inc., Haifa, Israel. bill@pluristem.com
authors.forename: William R
authors.initials: WR
authors.lastname: Prather
authors.forename: Amir
authors.initials: A
authors.lastname: Toren
authors.forename: Moran
authors.initials: M
authors.lastname: Meiron
authors.forename: Racheli
authors.initials: R
authors.lastname: Ofir
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschope
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Horwitz
mesh_terms: D000818:Animals; D002196:Capillaries / Q000473:pathology; D002448:Cell Adhesion; D005260:Female; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D016130:Immunophenotyping; D007511:Ischemia / Q000628:therapy*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D012039:Regional Blood Flow; D017154:Stromal Cells / Q000166:cytology*