Formation of a Vascular Regenerative Microenvironment Within Implantable Human Decellularized Adipose Tissue Bioscaffolds
Abstract
Cellular therapies targeted at stimulating therapeutic angiogenesis in individuals with critical limb ischemia (CLI) have been under intense investigation. Hematopoietic progenitor cells (HPC) derived from umbilical cord blood have been previously shown to support limb revascularization in animal models of CLI, despite limited cell survival at the site of ischemia. This study attempted to improve HPC survival after transplantation and prolong pro-angiogenic function using human decellularized adipose tissue (hDAT) as a novel cell delivery platform. Compared to HPC conventionally grown on tissue-cultured plastic, hDAT scaffolds were shown to promote viability and proliferation of seeded HPC, and had cell- instructive effects on HPC differentiation through increased expression of cell surface markers enriched on the monocyte/macrophage lineage. For in vivo transplantation studies in a surgically-induced model of CLI, hDAT-seeded scaffolds promoted an accelerated and sustained recovery in limb perfusion, improved functional limb use and increased CD31+ capillary density compared to unseeded hDAT controls.