scholarly journals Induced pluripotent stem cells are Japanese brand sources for therapeutic cells to pretrial clinical research

2020 ◽  
Vol 7 (1) ◽  
pp. 296-303
Author(s):  
Rupendra Shrestha

iPSCs are promising and have potential benefits for medical use, understanding human organogenesis, and cell therapy for advanced diseases. iPSCs are derived pluripotent cells which can further differentiate into functional human cell-lineages, such as neuronal, epithelial cells, cardiac cell, immune cell, and blood cells, etc. Thirteen years on, the discovery of iPSC has revolutionized the field of regenerative medicine, and also the number of clinical studies using iPSC has been growing rapidly worldwide. However, Japan is leading the race of iPSC-based studies and clinical trials due to government support. The Japanese government implemented the world’s fastest approval system and set to host first pretrial clinical studies using iPSC derived therapeutic products. Also, multinational companies of Japan are investing enormously in iPSC-based research for mobilization of iPSC-derived regenerative products to the research institution globally. This review presents an overview of iPSCs, potential benefits, commercialization of iPSC, iPSC-based pretrial clinical studies, and iPSC biobanking in Japan.

2020 ◽  
Vol 15 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Gaifang Wang ◽  
Maryam Farzaneh

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.


2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Hidetoshi Masumoto ◽  
Tadashi Ikeda ◽  
Tatsuya Shimizu ◽  
Teruo Okano ◽  
Ryuzo Sakata ◽  
...  

BACKGROUNDS: To realize cardiac regeneration with human induced pluripotent stem cells (hiPSCs), efficient differentiation from hiPSCs to defined cardiac cell populations (cardiomyocytes [CMs]/ endothelial cells [ECs]/ vascular mural cells [MCs]), and transplantation technique for fair engraftment are required. Recently, we reported that mouse ES cell-derived cardiac tissue sheet transplantation to rat myocardial infarction (MI) model ameliorated cardiac function after MI (Stem Cells, in press). Here we tried to extend this technique to hiPSCs. METHODS & RESULTS: We have reported an efficient cardiomyocyte differentiation protocol based on a monolayer culture (PLoS One, 2011), in which cardiac troponin-T (cTnT)-positive CMs robustly appeared with 50-80% efficiency. In this study, we further modified the protocol to induce vascular cells (ECs/MCs) together with CMs by vascular endothelial cell growth factor supplementation, resulted in proportional differentiation of cTnT+-CMs (62.7±11.7% of total cells), VE-cadherin+-ECs (7.8±4.9%) and PDGFRb+-MCs (18.2±11.0%) at differentiation day 15 (n=12). Then, these cells were transferred onto temperature-responsive culture dishes (UpCell dishes; CellSeed, Tokyo, Japan) to form cardiac tissue sheets including defined cardiac populations. After 4 days of culture, we successfully collected self-pulsating cardiac tissue sheets with 7.0×10 5 ±2.3 (n=12) of cells consisted of CMs (46.9±15.9% of total cells), ECs (4.1±3.7%), and MCs (22.5±15.7%). Three-layered hiPSC-derived cardiac sheets were transplanted to a MI model of athymic rat heart one week after MI. In transplantation group, echocardiogram showed a significant improvement of systolic function of left ventricle (fractional shortening: 22.6±5.0 vs 36.5±8.0%, p<0.001, n=20) and a decrease in akinetic length (20.8±9.7 vs 2.5±7.7%, p<0.001, n=20) (pre-treatment vs 4weeks after transplantation). We also succeeded in generation of larger sheets (1.6 inch diameter) with the same method. CONCLUTIONS: Transplantation of hiPSC-derived cardiac tissue sheets significantly ameliorates cardiac dysfunction after MI. Thus, we developed a valuable technological basis for hiPSC-based cardiac cell therapy.


2012 ◽  
Vol 24 (1) ◽  
pp. 286
Author(s):  
A. Dinnyes ◽  
M. K. Pirity ◽  
E. Gocza ◽  
P. Osteil ◽  
N. Daniel ◽  
...  

Pluripotent stem cells have the capacity to divide indefinitely and to differentiate to all the somatic tissues. They can be genetically manipulated in vitro by knocking in and out genes, therefore they serve as an excellent tool for gene-function studies and for the generation of models for human diseases. Since 1981, when the first mouse embryonic stem cell (ESC) line was generated, several attempts have been made to generate pluripotent stem cells from other species as it would help us to understand the differences and similarities of signaling pathways involved in pluripotency and differentiation, and would reveal whether the fundamental mechanism controlling self-renewal of pluripotent cells is conserved among different species. This review gives an overlook of embryonic and induced pluripotent stem cell (iPSCs) research in the rabbit which is one of the most relevant non-rodent species for animal models. To date, several lines of putative ESCs and iPSCs have been described in the rabbit. All expressed stem cell-associated markers and exhibited longevity and pluripotency in vitro, but none have been proven to exhibit full pluripotency in vivo. Moreover, similarly to several domestic species, markers used to characterize the putative ESCs are not fully adequate because studies in domestic species have revealed that they are not specific to the pluripotent inner cell mass. Future validation of rabbit pluripotent stem cells would benefit greatly from a reliable panel of molecular markers specific to pluripotent cells of the developing rabbit embryo. The status of isolation and characterization of the putative pluripotency genes in rabbit will be discussed. Using rabbit specific pluripotency genes we might be able to reprogram somatic cells and generate induced pluripotent stem cells more efficiently thus overcome some of the challenges towards harnessing the potential of this technology. This study was financed by EU FP7 (PartnErS, PIAP-GA-2008-218205; InduHeart, PEOPLE-IRG-2008-234390; InduVir, PEOPLE-IRG-2009-245808; RabPstem, PERG07-GA-2010-268422; PluriSys, HEALTH-2007-B-223485; AniStem, PIAP-GA-2011-286264), NKTH-OTKA-EU-7KP HUMAN-MB08-C-80-205; Plurabbit, OMFB-00130-00131/2010 ANR-NKTH/09-GENM-010-01.


2019 ◽  
Vol 31 (1) ◽  
pp. 218
Author(s):  
L. N. Moro ◽  
G. Amin ◽  
V. Furmento ◽  
A. Waisman ◽  
G. Neiman ◽  
...  

Cell reprogramming has been well described in mouse and human cells. The expression of specific microRNAs has demonstrated to be essential for pluripotent maintenance and cell differentiation, but not much information is available in domestic species. A single microRNA can regulate the expression of hundreds of mRNA targets, a property given by a short sequence (called “seed”) in positions 2 to 8 from the 5′ end that is complementary to the 3′ untranslated region (UTR) tail of specific mRNAs. We aimed to generate horse induced pluripotent stem cells (iPSC), characterise them, and evaluate the expression of different microRNAs (miR-302a, b, c, d, miR-205, miR-145, miR-9, miR-96, miR-125b, and miR-296) in pluripotency and differentiation. Both cell states were evaluated (pluripotency and differentiation) in order to understand more deeply the complex network of transcriptional regulation in different contexts but with the same genomic background. Two equine iPSC lines (named L2 and L3) were characterised after the reprogramming of equine fibroblasts with the 4 human Yamanaka factors (OCT-4, SOX-2, c-MYC, KLF4). The pluripotency of both lines was assessed by phosphatase alkaline activity, expression of OCT-4, NANOG, and REX1 by RT-PCR, and by immunofluorescence of OCT-4, SOX-2, and c-MYC. In vitro differentiation to embryo bodies (EB) showed the capacity of the iPSC to differentiate into ectodermal, endodermal, and mesodermal phenotypes. MicroRNA expression was analysed by quantitative RT-PCR and resulted in higher expression of the miR-302 family, miR-9, and miR-96 in L2 and L3v. fibroblasts (P ≤ 0.05), as previously shown in human pluripotent cells. Moreover, down-regulation of miR-145 and miR-205 was observed. After differentiation to EB, greater expression of miR-96 was observed in the EB compared with iPSC, and the expression of miR-205 was induced but only in the EB-L2. In addition, we performed in silico analysis of horse and human microRNAs. First, we compared the horse-miR-302/367 cluster with the human-miR-302/367 cluster and determined a 75% homology between them. Moreover, the seed region of the horse-miR-302 family resulted complementary to the 3′ UTR of horse cell cycle regulator genes CDK2, CYCLIN D1, and E2F1, and to the 3′ UTR of the RHOC gene, which is involved in the epithelial-mesenchymal transition. The miR-145 seed sequence was complementary to the 3′ UTR region of the OCT-4 and KLF-4 horse genes. With respect to miR-9 and miR-96, the seed sequence of these genes were complementary to the HES1 and PAX-6 genes. In all cases, the same gene targets were previously demonstrated in humans. In conclusion, we report the generation and characterization of equine iPSC and determined for the first time the expression of microRNAs in equine pluripotent cells. Moreover, several results led us to think that the horse microRNAs evaluated herein are highly conserved in sequence and function with respect to the human species. It will now be necessary to generate directed differentiations to derivatives of the 3 germ layers in order to strengthen our results. This is the first report to evaluate the expression and possible targets of microRNAs in pluripotent cells from domestic animals.


PLoS ONE ◽  
2011 ◽  
Vol 6 (2) ◽  
pp. e16734 ◽  
Author(s):  
Masataka Fujiwara ◽  
Peishi Yan ◽  
Tomomi G. Otsuji ◽  
Genta Narazaki ◽  
Hideki Uosaki ◽  
...  

iScience ◽  
2022 ◽  
pp. 103736
Author(s):  
Karlijn A.L. Hasaart ◽  
Freek Manders ◽  
Joske Ubels ◽  
Mark Verheul ◽  
Markus J. van Roosmalen ◽  
...  

2015 ◽  
Author(s):  
Courtney L Kagan ◽  
Nicholas E Banovich ◽  
Bryan J Pavlovic ◽  
Kristen Patterson ◽  
Irene Gallego Romero ◽  
...  

The advent of induced pluripotent stem cells (iPSCs) revolutionized Human Genetics by allowing us to generate pluripotent cells from easily accessible somatic tissues. This technology can have immense implications for regenerative medicine, but iPSCs also represent a paradigm shift in the study of complex human phenotypes, including gene regulation and disease. Yet, an unresolved caveat of the iPSC model system is the extent to which reprogrammed iPSCs retain residual phenotypes from their precursor somatic cells. To directly address this issue, we used an effective study design to compare regulatory phenotypes between iPSCs derived from two types of commonly used somatic precursor cells. We show that the cell type of origin only minimally affects gene expression levels and DNA methylation in iPSCs. Instead, genetic variation is the main driver of regulatory differences between iPSCs of different donors.


2012 ◽  
Vol 90 (3) ◽  
pp. 317-325 ◽  
Author(s):  
Stefano Pietronave ◽  
Maria Prat

Direct reprogramming of somatic cells into pluripotent cells is an emerging technology for creating patient-specific cells, and potentially opens new scenarios in medical and pharmacological fields. From the discovery of Shinya Yamanaka, who first obtained pluripotent cells from fibroblasts by retrovirus-derived ectopic expression of defined embryonic transcription factors, new methods have been developed to generate safe induced pluripotent stem (iPS) cells without genomic manipulations. This review will focus on the recent advances in iPS technology and their application in pharmacology and medicine.


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