In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells

Yoshimatsu, Masayoshi; Ohnishi, Hiroe; Zhao, Chengzhu; Hayashi, Yasuyuki; Kuwata, Fumihiko; Kaba, Shinji; Okuyama, Hideaki; Kawai, Yoshitaka; Hiwatashi, Nao; Kishimoto, Yo; Sakamoto, Tatsunori; Ikeya, Motoji; Omori, Koichi

doi:10.1016/j.scr.2021.102233

Cited by 20 publications

(9 citation statements)

References 64 publications

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“…The tumorigenic potential of iMSCs has been well assessed in previous research ( Harada et al, 2021 ; Yoshimatsu et al, 2021 ). These cells are typically induced from iNCCs using established protocols and fluorescent cell sorting techniques.…”

Section: Discussionmentioning

confidence: 99%

Selective vulnerability of human-induced pluripotent stem cells to dihydroorotate dehydrogenase inhibition during mesenchymal stem/stromal cell purification

Al-Akashi

Zujur

Kamiya

et al. 2023

Front. Cell Dev. Biol.

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The use of induced mesenchymal stem/stromal cells (iMSCs) derived from human induced pluripotent stem cells (hiPSCs) in regenerative medicine involves the risk of teratoma formation due to hiPSCs contamination in iMSCs. Therefore, eradicating the remaining undifferentiated hiPSCs is crucial for the effectiveness of the strategy. The present study demonstrates the Brequinar (BRQ)-induced inhibition of dihydroorotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine biosynthesis, selectively induces apoptosis, cell cycle arrest, and differentiation; furthermore, it promotes transcriptional changes and prevents the growth of 3-dimensional hiPSC aggregates. Contrastingly, BRQ-treated iMSCs showed no changes in survival, differentiation potential, or gene expression. The results suggest that BRQ is a potential agent for the effective purification of iMSCs from a mixed population of iMSCs and hiPSCs, which is a crucial step in successful iMSC-based therapy.

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Section: Discussionmentioning

confidence: 99%

Selective vulnerability of human-induced pluripotent stem cells to dihydroorotate dehydrogenase inhibition during mesenchymal stem/stromal cell purification

Al-Akashi

Zujur

Kamiya

et al. 2023

Front. Cell Dev. Biol.

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“…The first two principal components of this result were plotted using the ggscatter function ( https://rpkgs.datanovia.com/ggpubr/reference/ggscatter.html ) from the R package ggpubr ( https://cran.r-project.org/web/packages/ggpubr/index.html ), 107 and the weight of each gene’s contribution to the principal components were extracted for PC1 and PC2. The datasets used in the PCA were: GSM4616525, GSM4616526, GSM4616527 (dog iPS), GSM4617887, GSM4617889, GSM4617890, GSM4617891, GSM46 17895, GSM4617900, GSM4617901 (marmoset iPS), GSM4616532 (human iPS), GSM4616535, GSM4616536 (pigiPS) from study GSE152493, 95 GSM1287734, GSM1287735, GSM1287745, GSM1287746 (mouse ESC), GSM1287736, GSM1287747, GSM128 7748 (mouse iPS), GSM1287749, GSM1287750 (mouse fibroblasts, MEF) from GSE53212, 96 and GSM4303994, GSM4303995 (human naïve ES), GSM4304018, GSM4304019 (human primed ES) from GSE144994. 97 Note, that each analysis only induced genes that were annotated in all of the respective species.…”

Section: Methodsmentioning

confidence: 99%

“…The genes of the Corona virus disease related KEGG pathway were retrieved from the PathCards database ( https://pathcards.genecards.org ). The differential expression analysis was performed between RFe bat (this study) and mouse iPS cells (GSM1287736, GSM1287747 and GSM1287748 from Study GSE53212 95 using DESeq2. 105 The Corona virus disease-related genes were then illustrated with Cytoscape (Version 3.8.2) 111 using the STRING protein query with a 0.8 confidence score cutoff.…”

Section: Methodsmentioning

confidence: 99%

Bat pluripotent stem cells reveal unusual entanglement between host and viruses

Déjosez¹,

Marin²,

Hughes³

et al. 2023

Cell

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“…developed immunodeficient rat models [18,19]. Previous models have been used in the investigation of intestinal immunity to parasites [35], the creation of a humanized rat model of osteosarcoma [36], and the regeneration of rat laryngeal cartilage by human induced pluripotent stem cell-derived mesenchymal stem cells [37]. These previous studies clearly demonstrate the usefulness of immunodeficient rats.…”

Section: Plos Onementioning

confidence: 95%

A high-quality severe combined immunodeficiency (SCID) rat bioresource

Miyasaka

Wang²,

Hattori³

et al. 2022

PLoS ONE

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Immunodeficient animals are valuable models for the engraftment of exogenous tissues; they are widely used in many fields, including the creation of humanized animal models, as well as regenerative medicine and oncology. Compared with mice, laboratory rats have a larger body size and can more easily undergo transplantation of various tissues and organs. Considering the absence of high-quality resources of immunodeficient rats, we used the CRISPR/Cas9 genome editing system to knock out the interleukin-2 receptor gamma chain gene (Il2rg) in F344/Jcl rats—alone or together with recombination activating gene 2 (Rag2)—to create a high-quality bioresource that researchers can freely use: severe combined immunodeficiency (SCID) rats. We selected one founder rat with frame-shift mutations in both Il2rg (5-bp del) and Rag2 ([1-bp del+2-bp ins]/[7-bp del+2-bp ins]), then conducted mating to establish a line of immunodeficient rats. The immunodeficiency phenotype was preliminarily confirmed by the presence of severe thymic hypoplasia in Il2rg-single knockout (sKO) and Il2rg/Rag2-double knockout (dKO) rats. Assessment of blood cell counts in peripheral blood showed that the white blood cell count was significantly decreased in sKO and dKO rats, while the red blood cell count was unaffected. The decrease in white blood cell count was mainly caused by a decrease in lymphocytes. Furthermore, analyses of lymphocyte populations via flow cytometry showed that the numbers of B cells (CD3- CD45+) and natural killer cells (CD3- CD161+) were markedly reduced in both knockout rats. In contrast, T cells were markedly reduced but showed slightly different results between sKO and dKO rats. Notably, our immunodeficient rats do not exhibit growth retardation or gametogenesis defects. This high-quality SCID rat resource is now managed by the National BioResource Project in Japan. Our SCID rat model has been used in various research fields, demonstrating its importance as a bioresource.

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In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells

Cited by 20 publications

References 64 publications

Selective vulnerability of human-induced pluripotent stem cells to dihydroorotate dehydrogenase inhibition during mesenchymal stem/stromal cell purification

Selective vulnerability of human-induced pluripotent stem cells to dihydroorotate dehydrogenase inhibition during mesenchymal stem/stromal cell purification

Bat pluripotent stem cells reveal unusual entanglement between host and viruses

A high-quality severe combined immunodeficiency (SCID) rat bioresource

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