Project description:Here, we engineered functional EV-like nanovesicles (NVs) from human-induced pluripotent stem cells and highlight their potential as a functional surrogate for natural EVs for tissue repair. Proteome profiling of target cells further identified pathways implicated in angiogenesis (MYH10, AAMP, SLC3A2), cell survival (CCN2, RHEB, IGF2R, MFGE8), and fibroblast activation (CCN2, STAT3, COL1A1/2/4A2/12A1, ACTN1/4, ACTC1). This study demonstrates scalable generation of functional NVs and highlights their potential as a functional surrogate for natural EVs for tissue repair.
Project description:Cells producing adrenalin are largely derived from nerve-associated Schwann cell precursors via an intermediate progenitor “bridge” cell. We demonstrate that large numbers of chromaffin cells arise from peripheral glial stem cells, termed Schwann cell precursors (SCPs)
Project description:Schwann cells (SCs) are an absolute prerequisite for development of effective treatment of myelin disorders and nerve injuries. However, human sources of functional, myelinating SCs are extremely limited. Here, we have developed a novel, efficient strategy for producing directly an unlimited supply of functional human SCs via successful derivation of expandable Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs) (hPSC-SCPs). Functional and molecular characteristics of SCs from hPSC-SCPs (hPSC-SCP-SCs) appeared to be similar to those of authentic Schwann cells. As a novel therapeutic target, transplanted hPSC-SCP-SCs effectively promoted axonal regeneration through directly myelinating regenerated-axons in sciatic nerve injured mice. Here, we present hPSC-SCPs and hPSC-SCP-SCs as an outstanding resource to use for investigating human Schwann cell pathology and biology and for translational approaches to PNS and CNS repair and regeneration.
Project description:Here, human induced pluripotent stem cells (control-hiPSCs, CMT1A-hiPSCs, and PMP22-hiPSCs) were induced to differentiate to Schwann cells (control-SCs, CMT1A-SCs, and PMP22-SCs) through neural crest stage (control-NCSCs, CMT1A-NCSCs, and PMP22-NCSCs). We sequenced mRNA samples from Schwann cell differentiation of human pluripotent stem cells at 3 different stage to generate the gene expression profiles of these cells.
Project description:Establishing robust models of human myelinating Schwann cells is critical for studying peripheral nerve injury and disease. Stem cell differentiation has emerged as a key model of human cells and disease motivating development of Schwann cell differentiation protocols. Human embryonic stem cells (hESCs) are considered the ideal pluripotent cell but ethical concerns regarding their use have propelled the popularity of human induced pluripotent stem cells (hiPSCs). Given that the equivalence of hESCs and hiPSCs remains controversial, we sought to compare the molecular and functional equivalence of hESC- and hiPSC-derived Schwann cells generated with our previously reported protocol. We identified only modest transcriptome differences by RNA sequencing and insignificant proteome differences by antibody array. Additionally, both cell types comparably improved nerve regeneration and function in a chronic denervation and regeneration animal model. Our findings demonstrate that Schwann cells derived from hESCs and hiPSCs with our protocol are molecularly comparable and functionally equivalent.