Directed Differentiation of Notochord-like and Nucleus Pulposus-like Cells Using Human Pluripotent Stem Cells

Abstract

Highlights d A NOTO-EGFP reporter in hPSCs is established to monitor differentiation to NCLs d hPSCs can be induced into NCLs and NP-like cells using a defined protocol d hPSC-NP-like cells and human NP cells share high similarities in molecular signatures d Transplantation of hPSC-NP-like cells attenuates injuryinduced intervertebral disc degeneration

Acquisition of chromosome 1q duplication in parental and genome‐edited human‐induced pluripotent stem cell‐derived neural stem cells results in their higher proliferation rate in vitro and in vivo

“…NSCs derived from human ESCs and iPSCs are important vehicles for genetic and molecular therapies in the central nervous system. Genetic modifications of these cells allow for monitoring their differentiation progress, 36 improve our understanding of neural development and disease, 37 and may increase their potential for regenerative therapies 38 . To overcome the disadvantages of genetic modification methods based on random integration, we used ZFN technology for targeted genome modification in hiPSC‐NSCs.…”

Induced Pluripotent Stem Cell-Differentiated Chondrocytes Repair Cartilage Defect in a Rabbit Osteoarthritis Model

“…Recent fate-mapping studies in the mouse show that chondrocyte-like cells are derived from early notochord-like nucleus pulposus cells (NP cells) [ 57 ]. The efforts to derive notochord-like NP cells for chondrocyte differentiation have been also reported recently [ 58 ]. The advantages of NP cell-derived chondrocytes are that NP cells are the proceeding cells of the chondrocytes and could be easily identified.…”

Understanding embryonic development for cell‐based therapies of intervertebral disc degeneration: Toward an effort to treat disc degeneration subphenotypes

“…Therefore, NODAL shares type I and II receptors with Activin, also a member of the TGF‐β superfamily, and acts through a shared SMAD2/3 signaling pathway 44 . Accordingly, Activin is used to help differentiate pluripotent stem cells toward the notochord lineage 45‐48 . In addition, high levels of NODAL/SMAD2/3 signaling induce anterior fates, while lower levels of NODAL gradients drive mesoderm cell fate decisions in accordance with spatio‐temporal positioning 49 .…”

“…Thus, NODAL and WNT signaling pathways synergistically promote the formation of the primitive streak and drive cell lineage allocation within the mesoderm. Not surprisingly, activation of WNT signaling is also used to help differentiate pluripotent stem cells toward the notochord lineage 45‐48 …”

“…Correspondingly, ablation of the Noto ortholog ( flh ) in Zebrafish results in complete loss of the notochord 60 . Studies that aim to direct pluripotent stem cells into notochord‐like cells for tissue regeneration applications use FOXA2, T, and NOTO expression as markers to confirm that the cells are favoring a commitment toward the notochord lineage and not the paraxial and lateral plate mesoderm or endoderm lineages 45‐48 …”