title: Safety and biodistribution profile of placental-derived mesenchymal stromal cells (PLX-PAD) following intramuscular delivery.
abstract: The administration of mesenchymal stromal cells (MSCs) provides an exciting emerging therapeutic modality for the treatment of peripheral arterial disease, a condition that is associated with critical limb ischemia as its end stage. Placental-derived MSCs, termed PLX-PAD cells, are stable adhesive stromal cells isolated from full-term human placentae, cultured on carriers, and expanded in a bioreactor called the PluriX. These cells can be expanded in vitro without phenotypic or karyotypic changes. We studied the safety and biodistribution properties of PLX-PAD cells following intramuscular administration in NOD/SCID mice. No significant clinical signs, hematological and biochemical parameters, or major pathological changes were found in PLX-PAD-treated animals in comparison to vehicle controls. Several animals in the control and PLX-PAD-treated groups developed thymic malignant lymphoma, first seen after one month, as expected in this mouse strain. In addition, both groups developed spontaneous mesenteric vessel inflammation. Real-time quantitative polymerase chain reaction (RT-qPCR) demonstrated that distribution of PLX-PAD cells was confined to the injection site. Placental-derived MSCs remained in this site with gradual decrease in concentration during a three-month period. In view of these data, we conclude that the administration of PLX-PAD cells is not associated with any adverse effects in NOD/SCID mice.
authors.affiliation: Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Ramot
authors.forename: Moran
authors.initials: M
authors.lastname: Meiron
authors.forename: Amir
authors.initials: A
authors.lastname: Toren
authors.forename: Michal
authors.initials: M
authors.lastname: Steiner
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D016026:Bone Marrow Transplantation; D017690:Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006403:Hematologic Tests; D006614:Hindlimb / Q000098:blood supply / Q000473:pathology; D006651:Histocytochemistry; D006965:Hyperplasia / Q000473:pathology; D007273:Injections, Intramuscular; D007511:Ischemia / Q000628:therapy; D008297:Male; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009929:Organ Size; D010920:Placenta / Q000166:cytology*; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation*; D014018:Tissue Distribution