Placenta-Derived Mesenchymal Stromal-Like Cells Promote 3D-Engineered Muscle Tissue Differentiation and Vessel Network Maturation.

Placental-derived stromal-like cells (PLX-PAD) have been shown to facilitate muscle tissue recovery after injury and stimulate angiogenesis. This work assesses the impact of PLX-PAD cells on the vascularization and maturation of engineered skeletal muscle tissue. Specifically, their effects in direct co-culture with endothelial cells, pericytes, and myoblasts seeded within microporous 3D scaffolds are characterized. Additionally, the impact of hypoxic PLX-PAD cell-conditioned medium (CM) on vascularization and muscle differentiation of engineered tissue is monitored. Co-culture of PLX-PAD with myocytes stimulated myocyte differentiation while PLX-PAD CM promoted the formation of vascular networks. Implantation of a multi-culture system of vascularized human skeletal muscle tissue and PLX-PAD into a rectus abdominal defect in nude mice promoted myocyte differentiation, host vessel penetration, and tissue integration. These findings indicate the ability of placenta-derived cells to induce the formation of vascularized engineered muscle constructs with potential therapeutic applications.