scholarly journals Differentiation of Baboon (Papio anubis) Induced-Pluripotent Stem Cells into Enucleated Red Blood Cells

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1282 ◽  
Author(s):  
Emmanuel N. Olivier ◽  
Kai Wang ◽  
Joshua Grossman ◽  
Nadim Mahmud ◽  
Eric E. Bouhassira
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Human Cells ◽  
Large Animal Model ◽  
Large Animal ◽  
Papio Anubis ◽  
Large Animal Models ◽  
Induced Pluripotent

As cell culture methods and stem cell biology have progressed, the in vitro production of cultured RBCs (cRBCs) has emerged as a viable option to produce cells for transfusion or to carry therapeutic cargoes. RBCs produced in culture can be quality-tested either by xeno-transfusion of human cells into immuno-deficient animals, or by transfusion of autologous cells in immuno-competent models. Although murine xeno-transfusion methods have improved, they must be complemented by studies in immuno-competent models. Non-human primates (NHPs) are important pre-clinical, large animal models due to their high biological and developmental similarities with humans, including their comparable hematopoietic and immune systems. Among NHPs, baboons are particularly attractive to validate cRBCs because of the wealth of data available on the characteristics of RBCs in this species that have been generated by past blood transfusion studies. We report here that we have developed a method to produce enucleated cRBCs by differentiation of baboon induced pluripotent stem cells (iPSCs). This method will enable the use of baboons to evaluate therapeutic cRBCs and generate essential pre-clinical data in an immuno-competent, large animal model. Production of the enucleated baboon cRBCs was achieved by adapting the PSC-RED protocol that we previously developed for human cells. Baboon-PSC-RED is an efficient chemically-defined method to differentiate iPSCs into cRBCs that are about 40% to 50% enucleated. PSC-RED is relatively low cost because it requires no albumin and only small amounts of recombinant transferrin.

scholarly journals Generation of Integration-Free Porcine Induced Neural Stem Cells Using Sendai virus

2021 ◽  
Author(s):  
Warunya Chakritbudsabong ◽  
Ruttachuk Rungsiwiwut ◽  
Ladawan Sariya ◽  
Phakhin Juntahirun ◽  
Nattarun Chaisilp ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Sendai Virus ◽  
Large Animal ◽  
Large Animal Models ◽  
Induced Pluripotent ◽  
Induced Neural Stem Cells

Abstract Background The reprogramming of cells to induced neural stem cells (iNSCs), faster and safer to generate than induced pluripotent stem cells, holds tremendous promise for disease modeling and personalized cell-based therapies for neurological diseases. Porcine iNSCs (piNSCs) may serve as a disease model for human medicine, as pigs are one of the most successful large animal models in biomedical research. Thus, this study aimed to establish safe and efficient integration-free piNSC lines.Methods The integration-free piNSC lines were generated by reprogramming porcine fibroblasts using the Sendai virus (SeV).Results Here we report the successful generation of integration-free piNSC lines using the SeV, with a reprogramming efficiency of 0.4%. The piNSCs can be expanded for up to 40 passages and express high levels of NSC markers (PAX6, NESTIN, and SOX2). They can produce neurons and glia, expressing TUJ, MAP2, TH, and GFAP. No induced pluripotent stem cells developed during reprogramming, and the established piNSCs did not express OCT4. Hence, the SeV can reprogram porcine fibroblast without first going through an intermediate pluripotent stage.Conclusions With the SeV approach, we generated integration-free piNSCs that may be used to assess the efficacy and safety of iNSC-based clinical translation in humans.

scholarly journals Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cells from the Progenitor Cell Biology Consortium

2016 ◽  
Vol 7 (1) ◽  
pp. 110-125 ◽  
Author(s):  
Nathan Salomonis ◽  
Phillip J. Dexheimer ◽  
Larsson Omberg ◽  
Robin Schroll ◽  
Stacy Bush ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Progenitor Cell ◽  
Genomic Analysis ◽  
Induced Pluripotent

scholarly journals Generation of Porcine Induced Neural Stem Cells Using the Sendai Virus

2022 ◽  
Vol 8 ◽  
Author(s):  
Warunya Chakritbudsabong ◽  
Ladawan Sariya ◽  
Phakhin Jantahiran ◽  
Nattarun Chaisilp ◽  
Somjit Chaiwattanarungruengpaisan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Sendai Virus ◽  
Genetic Alterations ◽  
Human Medicine ◽  
Large Animal ◽  
Induced Pluripotent ◽  
Induced Neural Stem Cells

The reprogramming of cells into induced neural stem cells (iNSCs), which are faster and safer to generate than induced pluripotent stem cells, holds tremendous promise for fundamental and frontier research, as well as personalized cell-based therapies for neurological diseases. However, reprogramming cells with viral vectors increases the risk of tumor development due to vector and transgene integration in the host cell genome. To circumvent this issue, the Sendai virus (SeV) provides an alternative integration-free reprogramming method that removes the danger of genetic alterations and enhances the prospects of iNSCs from bench to bedside. Since pigs are among the most successful large animal models in biomedical research, porcine iNSCs (piNSCs) may serve as a disease model for both veterinary and human medicine. Here, we report the successful generation of piNSC lines from pig fibroblasts by employing the SeV. These piNSCs can be expanded for up to 40 passages in a monolayer culture and produce neurospheres in a suspension culture. These piNSCs express high levels of NSC markers (PAX6, SOX2, NESTIN, and VIMENTIN) and proliferation markers (KI67) using quantitative immunostaining and western blot analysis. Furthermore, piNSCs are multipotent, as they are capable of producing neurons and glia, as demonstrated by their expressions of TUJ1, MAP2, TH, MBP, and GFAP proteins. During the reprogramming of piNSCs with the SeV, no induced pluripotent stem cells developed, and the established piNSCs did not express OCT4, NANOG, and SSEA1. Hence, the use of the SeV can reprogram porcine somatic cells without first going through an intermediate pluripotent state. Our research produced piNSCs using SeV methods in novel, easily accessible large animal cell culture models for evaluating the efficacy of iNSC-based clinical translation in human medicine. Additionally, our piNSCs are potentially applicable in disease modeling in pigs and regenerative therapies in veterinary medicine.

scholarly journals Future perspective of induced pluripotent stem cells for diagnosis, drug screening and treatment of human diseases

2010 ◽  
Vol 104 (07) ◽  
pp. 39-44 ◽  
Author(s):  
Qizhou Lian ◽  
Yenyen Chow ◽  
Miguel Esteban ◽  
Duanqing Pei ◽  
Hung-Fat Tse
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Ips Cell ◽  
Cell Technology ◽  
Induced Pluripotent

SummaryRecent advances in stem cell biology have transformed the understanding of cell physiology and developmental biology such that it can now play a more prominent role in the clinical application of stem cell and regenerative medicine. Success in the generation of human induced pluripotent stem cells (iPS) as well as related emerging technology on the iPS platform provide great promise in the development of regenerative medicine. Human iPS cells show almost identical properties to human embryonic stem cells (ESC) in pluripotency, but avoid many of their limitations of use. In addition, investigations into reprogramming of somatic cells to pluripotent stem cells facilitate a deeper understanding of human stem cell biology. The iPS cell technology has offered a unique platform for studying the pathogenesis of human disease, pharmacological and toxicological testing, and cell-based therapy. Nevertheless, significant challenges remain to be overcome before the promise of human iPS cell technology can be realised.

scholarly journals Induced Pluripotent Stem Cells (iPSCs) and Gene Therapy: A New Era for the Treatment of Neurological Diseases

2021 ◽  
Vol 22 (24) ◽  
pp. 13674
Author(s):  
Giulia Paolini Sguazzi ◽  
Valentina Muto ◽  
Marco Tartaglia ◽  
Enrico Bertini ◽  
Claudia Compagnucci
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Recent Progress ◽  
Gene Editing ◽  
New Era ◽  
Induced Pluripotent

To date, gene therapy has employed viral vectors to deliver therapeutic genes. However, recent progress in molecular and cell biology has revolutionized the field of stem cells and gene therapy. A few years ago, clinical trials started using stem cell replacement therapy, and the induced pluripotent stem cells (iPSCs) technology combined with CRISPR-Cas9 gene editing has launched a new era in gene therapy for the treatment of neurological disorders. Here, we summarize the latest findings in this research field and discuss their clinical applications, emphasizing the relevance of recent studies in the development of innovative stem cell and gene editing therapeutic approaches. Even though tumorigenicity and immunogenicity are existing hurdles, we report how recent progress has tackled them, making engineered stem cell transplantation therapy a realistic option.

scholarly journals The Potential of Induced Pluripotent Stem Cells to Treat and Model Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Joseph M. Schulz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Animal Models ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Cells ◽  
Patient Specific ◽  
Specific Cell ◽  
Induced Pluripotent

An estimated 6.2 million Americans aged 65 or older are currently living with Alzheimer’s disease (AD), a neurodegenerative disease that disrupts an individual’s ability to function independently through the degeneration of key regions in the brain, including but not limited to the hippocampus, the prefrontal cortex, and the motor cortex. The cause of this degeneration is not known, but research has found two proteins that undergo posttranslational modifications: tau, a protein concentrated in the axons of neurons, and amyloid precursor protein (APP), a protein concentrated near the synapse. Through mechanisms that have yet to be elucidated, the accumulation of these two proteins in their abnormal aggregate forms leads to the neurodegeneration that is characteristic of AD. Until the invention of induced pluripotent stem cells (iPSCs) in 2006, the bulk of research was carried out using transgenic animal models that offered little promise in their ability to translate well from benchtop to bedside, creating a bottleneck in the development of therapeutics. However, with iPSC, patient-specific cell cultures can be utilized to create models based on human cells. These human cells have the potential to avoid issues in translatability that have plagued animal models by providing researchers with a model that closely resembles and mimics the neurons found in humans. By using human iPSC technology, researchers can create more accurate models of AD ex vivo while also focusing on regenerative medicine using iPSC in vivo. The following review focuses on the current uses of iPSC and how they have the potential to regenerate damaged neuronal tissue, in the hopes that these technologies can assist in getting through the bottleneck of AD therapeutic research.

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