Published Papers - Noguchi Hirofumi

Islet transplantation using donors after brain and cardiac death: A multicenter clinical trial in Japan

Anazawa, T; Marubashi, S; Kodama, S; Goto, M; Eguchi, H; Maruyama, M; Shimoda, M; Noguchi, H; Yamaguchi, T; Ito, T; Kenmochi, T; Gotoh, M

TRANSPLANTATION   107 ( 10 ) 84 - 84   2023.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Cytoprotective Effect of Pteryxin on Insulinoma MIN6 Cells Due to Antioxidant Enzymes Expression via Nrf2/ARE Activation

Junsei Taira, Ryuji Tsuda, Chika Miyagi-Shiohira, Hirofumi Noguchi, Takayuki Ogi

Antioxidants ( MDPI AG )  12 ( 3 ) 693 - 693   2023.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The low-level antioxidant activity of pancreatic islets causes type 1 diabetes due to oxidative stress, which is also the cause of failure in the pancreatic islets' isolation and cell transplantation. In our previous study, pteryxin was found to be a natural product as a nuclear factor-erythroid-2-related factor (Nrf2) activator. This study focused on elucidation that the potentiality of pteryxin can activate the antioxidant enzymes, even under oxidative stress, by hydrogen peroxide (H2O2). Pteryxin treated with mouse insulinoma MIN6 cells was enhanced the antioxidant gene expressions in the ARE (antioxidant response element) region for HO-1 (Heme Oxygenase-1), GCLC (Glutamate-cysteine ligase catalytic subunit), SOD1 (Super Oxide dismutase1), and Trxr1 (Thioredoxin reductase1), and those enzymes were also expressed during the nuclei transference of cytoplasmic Nrf2. In fact, the cells exposed to H2O2 concentrations of a half-cell lethal in the presence of pteryxin were then induced main antioxidant enzymes, HO-1, GCLC, and Trxr1 in the ARE region. The increased glutathione (GSH) levels associated with the GCLC expression also suggested to be cytoprotective against oxidative stress by activating the redox-metabolizing enzymes involving their increased antioxidant activity in the cells. In addition, Akt is a modulator for Nrf2, which may be responsible for the Nrf2 activation. These results allowed us to consider whether pteryxin or its synthesized congeners, an Nrf2 activator, is a potential preservative agent against islet isolation during cell transplantation.

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Protocol for the generation of human induced hepatic stem cells using Sendai virus vectors

Noguchi, H; Nakashima, Y; Watanabe, M; Matsushita, M; Tsukahara, M; Saitoh, I; Miyagi-Shiohira, C

STAR PROTOCOLS ( STAR Protocols )  3 ( 4 ) 101884 - 101884   2022.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Our recent study demonstrated the generation of induced tissue-specific stem/progenitor (iTS/iTP) cells by the transient overexpression of reprogramming factors combined with tissue-specific selection. Here, we present a protocol to reprogram human hepatocytes to generate human induced tissue-specific liver stem (iTS-L) cells. Human hepatocytes are transfected with Sendai virus vectors (SeV) expressing OCT3/4, SOX2, KLF4, and c-MYC. iTS-L cells continuously express mRNA of hepatocyte-specific markers (HNF1β and HNF4α) and do not form teratomas. For complete details on the use and execution of this protocol, please refer to Nakashima et al. (2022).1.

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Functional Evaluation of 3D Liver Models Labeled with Polysaccharide Functionalized Magnetic Nanoparticles

Miyamoto, Y; Koshidaka, Y; Murase, K; Kanno, S; Noguchi, H; Miyado, K; Ikeya, T; Suzuki, S; Yagi, T; Teramoto, N; Hayashi, S

MATERIALS ( Materials )  15 ( 21 ) 7823 - 7823   2022.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Establishing a rapid in vitro evaluation system for drug screening is essential for the development of new drugs. To reproduce tissues/organs with functions closer to living organisms, in vitro three-dimensional (3D) culture evaluation using microfabrication technology has been reported in recent years. Culture on patterned substrates with controlled hydrophilic and hydrophobic regions (Cell-ableTM) can create 3D liver models (miniature livers) with liver-specific Disse luminal structures and functions. MRI contrast agents are widely used as safe and minimally invasive diagnostic methods. We focused on anionic polysaccharide magnetic iron oxide nanoparticles (Resovist®) and synthesized the four types of nanoparticle derivatives with different properties. Cationic nanoparticles (TMADM) can be used to label target cells in a short time and have been successfully visualized in vivo. In this study, we examined the morphology of various nanoparticles. The morphology of various nanoparticles showed relatively smooth-edged spherical shapes. As 3D liver models, we prepared primary hepatocyte–endothelial cell heterospheroids. The toxicity, CYP3A, and albumin secretory capacity were evaluated in the heterospheroids labeled with various nanoparticles. As the culture period progressed, the heterospheroids labeled with anionic and cationic nanoparticles showed lower liver function than non-labeled heterospheroids. In the future, there is a need to improve the method of creation of artificial 3D liver or to design a low-invasive MRI contrast agent to label the artificial 3D liver.

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Induced hepatic stem cells are suitable for human hepatocyte production

Nakashima, Y; Miyagi-Shiohira, C; Saitoh, I; Watanabe, M; Matsushita, M; Tsukahara, M; Noguchi, H

ISCIENCE ( iScience )  25 ( 10 ) 105052 - 105052   2022.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Human hepatocytes were transfected with Sendai virus vectors (SeV) expressing OCT3/4, SOX2, KLF4, and C-MYC to produce hepatocyte-derived induced pluripotent stem cells (iPSCs). The messenger RNA (mRNA) expression of undifferentiated markers (passage 19-21) and hepatocyte-specific markers (HSMs) (passage 0-20) in 48 established hepatocyte-derived iPSC-like colonies was examined. Among the 48 clones, 10 clones continuously expressed HSM mRNA (HNF1β and HNF4α) in passage 0-20. The colonies which expressed HSMs (iTS-L cells: induced tissue-specific stem cells from liver) showed a different tendency in microarray and methylation analyses to fibroblast-derived iPSCs (strain: 201B7). iTS-L cells were less likely to form teratomas in mice than iPSCs (He). The iTS-L cells were differentiated into hepatocyte-like cells more efficiently than iPSCs (He) or iPSCs (201B7). These data suggest that SeV expressing OCT3/4, SOX2, KLF4, and C-MYC induce the generation of iPSCs and iTS-L cells.

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The Role of Genetically Modified Human Feeder Cells in Maintaining the Integrity of Primary Cultured Human Deciduous Dental Pulp Cells

Ibano, N; Inada, E; Otake, S; Kiyokawa, Y; Sakata, K; Sato, M; Kubota, N; Noguchi, H; Iwase, Y; Murakami, T; Sawami, T; Kakihara, Y; Maeda, T; Terunuma, M; Terao, Y; Saitoh, I

JOURNAL OF CLINICAL MEDICINE ( Journal of Clinical Medicine )  11 ( 20 )   2022.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Tissue-specific stem cells exist in tissues and organs, such as skin and bone marrow. However, their pluripotency is limited compared to embryonic stem cells. Culturing primary cells on plastic tissue culture dishes can result in the loss of multipotency, because of the inability of tissue-specific stem cells to survive in feeder-less dishes. Recent findings suggest that culturing primary cells in medium containing feeder cells, particularly genetically modified feeder cells expressing growth factors, may be beneficial for their survival and proliferation. Therefore, the aim of this study was to elucidate the role of genetically modified human feeder cells expressing growth factors in maintaining the integrity of primary cultured human deciduous dental pulp cells. Feeder cells expressing leukemia inhibitory factor, bone morphogenetic protein 4, and basic fibroblast growth factor were successfully engineered, as evidenced by PCR. Co-culturing with mitomycin-C-treated feeder cells enhanced the proliferation of newly isolated human deciduous dental pulp cells, promoted their differentiation into adipocytes and neurons, and maintained their stemness properties. Our findings suggest that genetically modified human feeder cells may be used to maintain the integrity of primary cultured human deciduous dental pulp cells.

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AP39, a Mitochondrial-Targeted H₂S Donor, Improves Porcine Islet Survival in Culture

Shinzato, M; Miyagi-Shiohira, C; Kuwae, K; Nishime, K; Tamaki, Y; Yonaha, T; Sakai-Yonaha, M; Yamasaki, I; Otsuka, R; Saitoh, I; Watanabe, M; Noguchi, H

JOURNAL OF CLINICAL MEDICINE ( Journal of Clinical Medicine )  11 ( 18 )   2022.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The rapid deterioration of transplanted islets in culture is a well-established phenomenon. We recently reported that pancreas preservation with AP39 reduces reactive oxygen species (ROS) production and improves islet graft function. In this study, we investigated whether the addition of AP39 to the culture medium could reduce isolated islet deterioration and improve islet function. Isolated islets from porcine pancreata were cultured with 400 nM AP39 or without AP39 at 37 °C. After culturing for 6-72 h, the islet equivalents of porcine islets in the AP39(+) group were significantly higher than those in the AP39(-) group. The islets in the AP39(+) group exhibited significantly decreased levels of ROS production compared to the islets in the AP39(-) group. The islets in the AP39(+) group exhibited significantly increased mitochondrial membrane potential compared to the islets in the AP39(-) group. A marginal number (1500 IEs) of cultured islets from each group was then transplanted into streptozotocin-induced diabetic mice. Culturing isolated islets with AP39 improved islet transplantation outcomes in streptozotocin-induced diabetic mice. The addition of AP39 in culture medium reduces islet deterioration and furthers the advancements in β-cell replacement therapy.

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Pancreas Preservation in Modified Histidine-lactobionate Solution Is Superior to That in University of Wisconsin Solution for Porcine Islet Isolation

Sakai-Yonaha, M; Miyagi-Shiohira, C; Kuwae, K; Tamaki, Y; Nishime, K; Yonaha, T; Saitoh, I; Watanabe, M; Noguchi, H

TRANSPLANTATION ( Transplantation )  106 ( 9 ) 1770 - 1776   2022.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: We previously reported that modified extracellular-type trehalose-containing Kyoto (MK) solution, which contains a trypsin inhibitor (ulinastatin), significantly improved the islet yield compared with University of Wisconsin (UW) preservation, which is the gold standard for organ preservation for islet isolation. In this study, we evaluated the efficiency of a modified histidine-lactobionate (MHL) solution in addition to UW or MK solution. The MHL solution has a high sodium-low potassium composition with low viscosity compared with the UW solution. Moreover, similar to MK solution, MHL solution also contains ulinastatin. METHODS: Porcine pancreata were preserved in UW, MK, or MHL solution, followed by islet isolation. An optimized number (1500 IE) of isolated islets from each group were then transplanted into streptozotocin-induced diabetic mice. RESULTS: The islet yield before and after purification was significantly higher in the MHL group than in the UW group. On the contrary, the islet yield before and after purification was not significantly different between the MHL and MK groups. Preserving the porcine pancreata in MHL solution improved the outcome of islet transplantation in streptozotocin-induced diabetic mice compared with that in UW solution. CONCLUSIONS: Pancreas preservation with MHL solution preserves islet function better than UW solution. The effect of MHL solution is similar to that of MK solution, suggesting that MHL solution can be used as an alternative to MK solution for pancreatic islet transplantation.

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Initiation of dialysis for kidney graft failure: A retrospective single-center cohort study

Taira, H; Noguchi, H; Ueki, K; Kaku, K; Tsuchimoto, A; Okabe, Y; Ohya, Y; Nakamura, M

THERAPEUTIC APHERESIS AND DIALYSIS ( Therapeutic Apheresis and Dialysis )  26 ( 4 ) 806 - 814   2022.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Pancreas Preservation with a Neutrophil Elastase Inhibitor, Alvelestat, Contributes to Improvement of Porcine Islet Isolation and Transplantation

Otsuka, R; Miyagi-Shiohira, C; Kuwae, K; Nishime, K; Tamaki, Y; Yonaha, T; Sakai-Yonaha, M; Yamasaki, I; Shinzato, M; Saitoh, I; Watanabe, M; Noguchi, H

JOURNAL OF CLINICAL MEDICINE ( Journal of Clinical Medicine )  11 ( 15 )   2022.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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For pancreatic islet transplantation, pancreas procurement, preservation, and islet isolation destroy cellular and non-cellular components and activate components such as resident neutrophils, which play an important role in the impairment of islet survival. It has been reported that inhibitors of neutrophil elastase (NE), such as sivelestat and α1-antitrypsin, could contribute to improvement of islet isolation and transplantation. In this study, we investigated whether pancreatic preservation with alvelestat, a novel NE inhibitor, improves porcine islet yield and function. Porcine pancreata were preserved with or without 5 μM alvelestat for 18 h, and islet isolation was performed. The islet yields before and after purification were significantly higher in the alvelestat (+) group than in the alvelestat (-) group. After islet transplantation into streptozotocin-induced diabetic mice, blood glucose levels reached the normoglycemic range in 55% and 5% of diabetic mice in the alvelestat (+) and alvelestat (-) groups, respectively. These results suggest that pancreas preservation with alvelestat improves islet yield and graft function and could thus serve as a novel clinical strategy for improving the outcome of islet transplantation.

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Clinical Islet Transplantation Covered by Health Insurance in Japan

Noguchi, H

JOURNAL OF CLINICAL MEDICINE ( Journal of Clinical Medicine )  11 ( 14 )   2022.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Pancreatic islet transplantation is a treatment option for patients with type 1 diabetes mellitus and has been performed in various countries [...].

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Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm

Sato, M; Saitoh, I; Kiyokawa, Y; Iwase, Y; Kubota, N; Ibano, N; Noguchi, H; Yamasaki, Y; Inada, E

CELLS ( Cells )  10 ( 12 ) 3338 - 3338   2021.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Alkaline phosphatase (ALP) is a ubiquitous membrane-bound glycoprotein capable of providing inorganic phosphate by catalyzing the hydrolysis of organic phosphate esters, or removing inorganic pyrophosphate that inhibits calcification. In humans, four forms of ALP cDNA have been cloned, among which tissue-nonspecific ALP (TNSALP) (TNSALP) is widely distributed in the liver, bone, and kidney, making it an important marker in clinical and basic research. Interestingly, TNSALP is highly expressed in juvenile cells, such as pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells (iPSCs)) and somatic stem cells (i.e., neuronal stem cells and bone marrow mesenchymal stem cells). Hypophosphatasia is a genetic disorder causing defects in bone and tooth development as well as neurogenesis. Mutations in the gene coding for TNSALP are thought to be responsible for the abnormalities, suggesting the essential role of TNSALP in these events. Moreover, a reverse-genetics-based study using mice revealed that TNSALP is important in bone and tooth development as well as neurogenesis. However, little is known about the role of TNSALP in the maintenance and differentiation of juvenile cells. Recently, it was reported that cells enriched with TNSALP are more easily reprogrammed into iPSCs than those with less TNSALP. Furthermore, in bone marrow stem cells, ALP could function as a "signal regulator" deciding the fate of these cells. In this review, we summarize the properties of ALP and the background of ALP gene analysis and its manipulation, with a special focus on the potential role of TNSALP in the generation (and possibly maintenance) of juvenile cells.

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In vivo evaluation of GG2-GG1/A2 element activity in the insulin promoter region using the CRISPR-Cas9 system

Noguchi, H; Miyagi-Shiohira, C; Kinjo, T; Saitoh, I; Watanabe, M

SCIENTIFIC REPORTS ( Scientific Reports )  11 ( 1 ) 20290 - 20290   2021.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The insulin promoter is regulated by ubiquitous as well as pancreatic β-cell-specific transcription factors. In the insulin promoter, GG2-GG1/A2-C1 (bases - 149 to - 116 in the human insulin promoter) play important roles in regulating β-cell-specific expression of the insulin gene. However, these events were identified through in vitro studies, and we are unaware of comparable in vivo studies. In this study, we evaluated the activity of GG2-GG1/A2 elements in the insulin promoter region in vivo. We generated homozygous mice with mutations in the GG2-GG1/A2 elements in each of the Ins1 and Ins2 promoters by CRISPR-Cas9 technology. The mice with homozygous mutations in the GG2-GG1/A2 elements in both Ins1 and Ins2 were diabetic. These data suggest that the GG2-GG1/A2 element in mice is important for Ins transcription in vivo.

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Preservation of pancreas in the University of Wisconsin solution supplemented with AP39 reduces reactive oxygen species production and improves islet graft function

Nishime, K; Miyagi-Shiohira, C; Kuwae, K; Tamaki, Y; Yonaha, T; Sakai-Yonaha, M; Saitoh, I; Watanabe, M; Noguchi, H

AMERICAN JOURNAL OF TRANSPLANTATION ( American Journal of Transplantation )  21 ( 8 ) 2698 - 2708   2021.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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RNA analysis based on a small number of manually isolated fixed cells (RNA-snMIFxC) to profile stem cells from human deciduous tooth-derived dental pulp cells

Inada, E; Saitoh, I; Kubota, N; Iwase, Y; Kiyokawa, Y; Noguchi, H; Yamasaki, Y; Sato, M

BIOLOGICAL PROCEDURES ONLINE ( Biological Procedures Online )  23 ( 1 ) 12 - 12   2021.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Expression of stemness factors, such as octamer-binding transcription factor 3/4 (OCT3/4), sex determining region Y-box 2 (SOX2), and alkaline phosphatase (ALP) in human deciduous tooth-derived dental pulp cells (HDDPCs) can be assessed through fixation and subsequent immuno- or cytochemical staining. Fluorescence-activated cell sorting (FACS), a powerful system to collect cells of interest, is limited by the instrument cost and difficulty in handling. Magnetic-activated cell sorting is inexpensive compared to FACS, but is confined to cells with surface expression of the target molecule. In this study, a simple and inexpensive method was developed for the molecular analysis of immuno- or cytochemically stained cells with intracellular expression of a target molecule, through isolation of a few cells under a dissecting microscope using a mouthpiece-controlled micropipette. RESULTS: Two or more colored cells (~ 10), after staining with a chromogen such a 3,3'-diaminobenzidine, were successfully segregated from unstained cells. Expression of glyceraldehyde 3-phosphate dehydrogenase, a housekeeping gene, was discernible in all samples, while the expression of stemness genes (such as OCT3/4, SOX2, and ALP) was confined to positively stained cells. CONCLUSION: These findings indicate the fidelity of these approaches in profiling cells exhibiting cytoplasmic or nuclear localization of stemness-specific gene products at a small-scale.

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Induced Tissue-Specific Stem Cells (iTSCs): Their Generation and Possible Use in Regenerative Medicine

Saitoh, I; Sato, M; Kiyokawa, Y; Inada, E; Iwase, Y; Ibano, N; Noguchi, H

PHARMACEUTICS ( Pharmaceutics )  13 ( 6 ) 780 - 780   2021.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Induced tissue-specific stem cells (iTSCs) are partially reprogrammed cells which have an intermediate state, such as progenitors or stem cells. They originate from the de-differentiation of differentiated somatic cells into pluripotent stem cells, such as induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), or from the differentiation of undifferentiated cells. They show a limited capacity to differentiate and a morphology similar to that of somatic cell stem cells present in tissues, but distinct from that of iPSCs and ESCs. iTSCs can be generally obtained 7 to 10 days after reprogramming of somatic cells with Yamanaka's factors, and their fibroblast-like morphology remains unaltered. iTSCs can also be obtained directly from iPSCs cultured under conditions allowing cellular differentiation. In this case, to effectively induce iTSCs, additional treatment is required, as exemplified by the conversion of iPSCs into naïve iPSCs. iTSCs can proliferate continuously in vitro, but when transplanted into immunocompromised mice, they fail to generate solid tumors (teratomas), implying loss of tumorigenic potential. The low tendency of iTSCs to elicit tumors is beneficial, especially considering applications for regenerative medicine in humans. Several iTSC types have been identified, including iTS-L, iTS-P, and iTS-D, obtained by reprogramming hepatocytes, pancreatic cells, and deciduous tooth-derived dental pulp cells, respectively. This review provides a brief overview of iPSCs and discusses recent advances in the establishment of iTSCs and their possible applications in regenerative medicine.

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Pancreas preservation with amphotericin B deteriorates islet yield for porcine islet isolation

Sawada, S; Miyagi-Shiohira, C; Kuwae, K; Tamaki, Y; Nishime, K; Sakai-Yonaha, M; Yonaha, T; Saitoh, I; Watanabe, M; Noguchi, H

XENOTRANSPLANTATION ( Xenotransplantation )  28 ( 4 ) e12690   2021.04 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Amphotericin B is a crucial agent in the management of serious systemic fungal infections. It is also known to be cytotoxic. In this study, we evaluated the effect of amphotericin B added to the preservation solution on islet yield during islet isolation. METHODS: Porcine pancreata were preserved in the preservation solution with or without amphotericin B (0.25 μg/mL) for approximately 18 hours at 4°C, and then islet isolation was performed. An optimized number (1750 IE) of isolated islets from each group were transplanted into streptozotocin-induced diabetic mice. The culture of isolated islets and acinar tissue with amphotericin B was also evaluated. RESULTS: The islet yield before and after purification in the amphotericin B (-) group was significantly higher than that in the amphotericin B (+) group. After islet transplantation into diabetic mice, blood glucose levels reached the normoglycemic range, with 50% and 0% of that of the diabetic mice in the amphotericin B (-) and amphotericin B (+) groups, respectively. In the culture study, amphotericin B was found to be cytotoxic to porcine islets and acinar tissue. CONCLUSIONS: Amphotericin B added to the preservation solution deteriorates islet yield during porcine islet isolation. Thus, the use of amphotericin B should be considered carefully for the preservation of the pancreas for islet isolation and islet culture before islet transplantation.

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Pancreas preservation in extracellular-type p38 inhibitor-containing solution improves islet yield for porcine islet isolation

Yonaha, T; Miyagi-Shiohira, C; Kuwae, K; Tamaki, Y; Nishime, K; Sakai-Yonaha, M; Saitoh, I; Watanabe, M; Noguchi, H

XENOTRANSPLANTATION ( Xenotransplantation )  28 ( 2 ) e12661   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Gene Expression in Pancreatic Cancer-Like Cells and Induced Pancreatic Stem Cells Generated by Transient Overexpression of Reprogramming Factors

Miyagi-Shiohira, C; Saitoh, I; Watanabe, M; Noguchi, H

JOURNAL OF CLINICAL MEDICINE ( Journal of Clinical Medicine )  10 ( 3 ) 1 - 12   2021.01 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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We previously reported that transient overexpression of reprogramming factors can be used to generate induced pluripotent stem (iPS) cells, induced tissue-specific stem (iTS) cells, and fibroblast-like (iF) cells from pancreatic tissue. iF cells have tumorigenic ability and behave similarly to pancreatic cancer cells. In this study, we analyzed gene expression in iF cells and iTS-P cells (iTS cells from pancreatic tissue) via microarray analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression levels of the Mybl2 and Lyn genes, which are reported to be oncogenes, were significantly higher in iF cells than in iTS-P cells. The expression level of Nestin, which is expressed in not only pancreatic progenitor cells but also pancreatic ductal adenocarcinomas, was also higher in iF cells than in iTS-P cells. Itgb6 and Fgf13, which are involved in the pathogenesis of diseases such as cancer, exhibited higher expression levels in iF cells than in iTS-P cells. Unexpectedly, the expression levels of genes related to epithelial-mesenchymal transition (EMT), except Bmp4, were lower in iF cells than in iTS-P cells. These data suggest that the Mybl2, Lyn, Nestin, Itgb6, and Fgf13 genes could be important biomarkers to distinguish iTS-P cells from iF cells.

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Drug-Induced Naïve iPS Cells Exhibit Better Performance than Primed iPS Cells with Respect to the Ability to Differentiate into Pancreatic β-Cell Lineage.

Kiyokawa Y, Sato M, Noguchi H, Inada E, Iwase Y, Kubota N, Sawami T, Terunuma M, Maeda T, Hayasaki H, Saitoh I

Journal of clinical medicine   9 ( 9 )   2020.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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