PLacental eXpanded (PLX) cells are placenta-derived, mesenchymal-like adherent stromal cells that may be administered to patients without the need for HLA-matching. This is possible because of the cells’ low immunogenicity and immune-modulatory properties. Accumulated data from multiple in vitro and in vivo experiments indicate that these cells have the capacity to release soluble biomolecules, such as cytokines, chemokines and growth factors, which act in a paracrine or endocrine manner to facilitate healing of damaged tissue. The secreted therapeutic factors reach the target tissue through the bloodstream and initiate the healing process, while the cells remain in the muscle into which they were injected.
Accumulated data from in vitro studies and from in vivo preclinical models of peripheral artery disease show that PLX-PAD secretes proteins that stimulate growth of new blood vessels to bypass obstructed ones. The secreted proteins may also enable extracellular matrix remodeling to allow for vascularization of tissues. It is thought that PLX-PAD accelerates the healing of injured muscle by stimulating angiogenesis, as well as by additional mechanisms that include secretion of proteins to induce muscle tissue regeneration and reduce connective tissue deposition; these result in improved muscle function and reduced scarring. PLX-PAD has also been shown to secrete proteins that regulate the immune system and modulate inflammation.
Proteins secreted by PLX-PAD include secreted proangiogenic proteins such as VEGF, angiogenin and angiopoietin 1. Additional secreted proteins include those which support muscle regeneration and are anti-fibrotic, such as galectin-1 and osteopontin, and immunomodulatory proteins, such as IL-6 and IL-8.
PLX-R18’s unique profile of secreted cytokines affects the maintenance of the hematopoietic niche, the renewal and differentiation of hematopoietic cells, and the mobilization of differentiated blood cells into peripheral blood. Therapeutic proteins secreted by the cells include GCSF, MCP-1, IL-6 and IL-8. Animal studies have shown that PLX-R18 secrete proteins that stimulate damaged bone marrow to secrete endogenous regenerative proteins and recover the ability to produce blood cells.