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 and/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 accelerate the healing of injured muscle by mechanisms that include secretion of proteins to induce muscle tissue regeneration and reduce connective tissue deposition in addition to stimulating angiogenesis to promote tissue regeneration resulting 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 proteins which support muscle regeneration such as decorin, HGF, galectin-1 and osteopontin, and immunomodulatory proteins, such as IDO and PD-L1 as well as secreted proangiogenic proteins such as VEGF, angiogenin and angiopoietin 1.
PLX-R18’s unique profile of secreted cytokines may affect 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. Both human and animal studies have demonstrated the potential of PLX-R18 to improve the recovery of blood cell production.
PLX-Immune cell’s secretion profile is altered during the 3D cell expansion procedure. The secreted cytokines have showed the ability to affect the proliferation of over 50 lines of human cancerous cells.
Therapeutic proteins secreted by the cells affect angiogenesis, immune activation, proliferation and metastasis.