“Footprint-Free” Human Induced Pluripotent Stem Cell-Derived Astrocytes for In Vivo Cell-Based Therapy

Abstract

The generation of human induced pluripotent stem cells (hiPSC) from somatic cells has enabled the possibility to provide patient-specific hiPSC for cell-based therapy, drug discovery, and other translational applications. Two major obstacles in using hiPSC for clinical application reside in the risk of genomic modification when they are derived with viral transgenes and risk of teratoma formation if undifferentiated cells are engrafted. In this study, we report the generation of ''footprint-free'' hiPSC-derived astrocytes. These are efficiently generated, have anatomical and physiological characteristics of fully differentiated astrocytes, maintain homing characteristics typical of stem cells, and do not give rise to teratomas when engrafted in the brain. Astrocytes can be obtained in sufficient numbers, aliquoted, frozen, thawed, and used when needed. Our results show the feasibility of differentiating astrocytes from ''footprint-free'' iPSC. These are suitable for clinical cell-based therapies as they can be induced from patients' specific cells, do not require viral vectors, and are fully differentiated. ''Footprint-free'' hiPSC-derived astrocytes represent a new potential source for therapeutic use for cell-based therapy, including treatment of high-grade human gliomas, and drug discovery.

Inducing pluripotency in vitro: recent advances and highlights in induced pluripotent stem cells generation and pluripotency reprogramming

“…Human induced pluripotent stem cells hold great promise for tailored cell-based therapies. Functional hiPSC derivatives such as astrocytes, dopaminergic neurons, retinal pigment epithelium cells, adipocyte progenitors, insulin-producing islet-like clusters, bone substitutes, hepatocytes, melanocytes, erythroblasts, cardiomyocytes and red blood cells have already been generated (127)(128)(129)(130)(131)(132)(133)(134)(135)(136)(137). Considering damaged tissues account for many chronic illnesses, such as neurodegenerative diseases, retinal degeneration, muscular dystrophy and myocardial infarction, patient-specific hiPSC derivatives can be a suitable therapeutic choice.…”

MicroRNA Replacing Oncogenic Klf4 and c-Myc for Generating iPS Cells via CationizedPleurotus eryngiiPolysaccharide-based Nanotransfection

“…14 Searching for alternative strategy to induce pluripotency without incurring genetic change has thus become the focus of intense research effort. To this end, several strategies, such as excisable vectors, 15 reprogramming proteins, 16 microRNAs, 17,18 nonintegrating plasmids, 19 modified RNA, and RNA virus, 20 have been designed to avoid genomic modification as much as possible.…”

Paving the Way Toward Complex Blood-Brain Barrier Models Using Pluripotent Stem Cells

“…Another study by Mormone et al used initial SMAD inhibition in their protocol followed by JAK/STAT activation and reported the generation of 60% GFAP-positive astrocytes. To enhance the purity of the astrocytes, the cells were then magnetic-activated cell sorted by using the astrocyte marker A2B5, which resulted in a purity of 95% GFAP-positive astrocytes [68,69].…”