ArticleJournal of visualized experiments : JoVE2025
Defined Xenofree Reprogramming of Cord Blood Progenitors to Induced Pluripotent and Blastomere-Like Stem Cells.
Article in Journal of visualized experiments : JoVE, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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3 authors.
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Abstract
Human cord blood (CB) myeloid progenitor reprogramming to a high-fidelity human induced pluripotent stem cell (hiPSC) state can be achieved using non-integrating episomal vectors and stromal signals. These conventional, primed CB-hiPSC lines can subsequently be chemically reverted with high efficiencies to a blastomere-like Tankyrase/PARP Inhibitor-Regulated Naive Stem Cell (TIRN-SC) state with functional totipotency. PARP-regulated TIRN-SCs are human stem cells with high epigenetic plasticity, stable epigenomic imprints, and have greater differentiation potency than conventional, lineage-primed hiPSCs. Here, optimized XF/FF methods are outlined for efficient mesenchymal stroma-activated episomal reprogramming of CD34+ CD33+ CB myeloid progenitors into conventional XF/FF hiPSC. TIRN reversion reproducibly potentiated XF/FF conventional hiPSC to adopt transcriptional, epigenetic, and functional features of cleavage-stage human embryo cells with decreased lineage-primed gene expression. We validated that TIRN-reverted CB-derived XF-hiPSC displayed marked improvement in directed multi-lineage differentiation (including hematovascular lineages) across a broad repertoire of genetically independent backgrounds. These methods serve as a first step for generating cGMP-compliant TIRN-SC lines for clinical-grade HLA-defined 'Universal' donor TIRN-SC (UTIRN-SC) banks. The derivation of UTIRN-SC lines with improved differentiation versatility from CD34+ CD33+ CB progenitors could have a high impact on regenerative medicine. For example, UTIRN-SCs could generate tissue banks of HLA-defined, cryo-preserved cardiac, vascular, and neural donor progenitors for comprehensive multi-lineage "off-the-shelf" cellular therapies.
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