In Vivo Elucidation of PLX-PAD Cell Mechanism of Action in the HLI Mouse Model

Peripheral artery disease (PAD) is a vascular disease in which there is a partial or total blockage of the blood supply to a limb, leading to hypoxia in the tissue. Pluristem’s PLX-PAD cells, derived from human term placentae and grown under GMP conditions, are in ongoing clinical studies for the PAD indication. This study analyzes the dose response to PLX-PAD cell treatment and compares efficacy at different injection sites and methods of administration, using the hind limb ischemia (HLI) murine model. We identify the minimal cell dose required for blood flow recovery, and use results of comparative injection sites and administration methods to provide clues for the PLX-PAD mechanism of action. Injections in the leg contralateral to HLI induction demonstrate treatment potency, indicating an endocrine mechanism of action. Injection of PLX-PAD cells is more potent than cell lysate, indicating that intact cells are required for full potency of treatment. This is likely due to the continual release of cytokines from cells, as well as due to the fact that cells respond to their microenvironment and change their secretory profile accordingly.