Vascularized cell-based device for restoring physiological homeostasis

University Of Louisville, Louisville KY

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Abstract

? DESCRIPTION (provided by applicant): Cell source and vascularization are two challenges to successful cell-based therapy. In this proposal we present an enabling technology for the vascularization of physiologically restored parenchymal cells derived from genetically deficient induced pluripotent stem cells (iPSC). As a proof-of-principle we have restored the low-density lipoprotein receptor (LDLR) feedback endocytosis in Familial Hypercholesterolemia (FH) iPSC. We will derive restored hepatocyte-like cells (HLC) and combine them with a unique stromal and vascularization cell source isolated from adipose tissue, known as the stromal vascular fraction (SVF). The objective of this proposal is to determine the capacity of an ectopic cell-based apheresis and metabolism device to modulate circulating LDL cholesterol (LDL-C) under hypercholesterolemic conditions. We will pursue this objective through the following Specific Aims: Aim 1: Determine the apheresis device LDL-C metabolism function. In this Aim we will investigate our device design for LDL-C internalization and metabolism, parenchymal cell survival, device vascularization and residual pluripotent cell elimination. Aim 2: Determine the apheresis device capacity to modulate circulating LDL-C. In this Aim we will investigate the capacity of the device to engraft, modulate LDL-C levels and produce human circulating proteins.