Large Animal Models for the Clinical Application of Human Induced Pluripotent Stem Cells

2019 ◽  
Vol 28 (19) ◽  
pp. 1288-1298 ◽  
Author(s):  
Xiaoqiang Cong ◽  
Shang-Min Zhang ◽  
Matthew W. Ellis ◽  
Jiesi Luo
Keyword(s):  
Stem Cells ◽  
Animal Models ◽  
Induced Pluripotent Stem Cells ◽  
Clinical Application ◽  
Pluripotent Stem Cells ◽  
Large Animal ◽  
Large Animal Models ◽  
Induced Pluripotent

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 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 Human Embryos, Induced Pluripotent Stem Cells, and Organoids: Models to Assess the Effects of Environmental Plastic Pollution

2021 ◽  
Vol 9 ◽  
Author(s):  
Dragana Miloradovic ◽  
Dragica Pavlovic ◽  
Marina Gazdic Jankovic ◽  
Sandra Nikolic ◽  
Milos Papic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Animal Models ◽  
Induced Pluripotent Stem Cells ◽  
Drug Screening ◽  
Pluripotent Stem Cells ◽  
New Technologies ◽  
Human Embryos ◽  
Plastic Pollution ◽  
Potential Health ◽  
Induced Pluripotent

For a long time, animal models were used to mimic human biology and diseases. However, animal models are not an ideal solution due to numerous interspecies differences between humans and animals. New technologies, such as human-induced pluripotent stem cells and three-dimensional (3D) cultures such as organoids, represent promising solutions for replacing, refining, and reducing animal models. The capacity of organoids to differentiate, self-organize, and form specific, complex, biologically suitable structures makes them excellent in vitro models of development and disease pathogenesis, as well as drug-screening platforms. Despite significant potential health advantages, further studies and considerable nuances are necessary before their clinical use. This article summarizes the definition of embryoids, gastruloids, and organoids and clarifies their appliance as models for early development, diseases, environmental pollution, drug screening, and bioinformatics.

scholarly journals Human Induced Pluripotent Stem Cells as a Screening Platform for Drug-Induced Vascular Toxicity

2021 ◽  
Vol 12 ◽  
Author(s):  
Chengyi Tu ◽  
Nathan J. Cunningham ◽  
Mao Zhang ◽  
Joseph C. Wu
Keyword(s):  
Stem Cells ◽  
Animal Models ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Vascular Pathology ◽  
Barrier Dysfunction ◽  
Drug Induced ◽  
Significant Discrepancy ◽  
Vascular Toxicity ◽  
Induced Pluripotent

Evaluation of potential vascular injury is an essential part of the safety study during pharmaceutical development. Vascular liability issues are important causes of drug termination during preclinical investigations. Currently, preclinical assessment of vascular toxicity primarily relies on the use of animal models. However, accumulating evidence indicates a significant discrepancy between animal toxicity and human toxicity, casting doubt on the clinical relevance of animal models for such safety studies. While the causes of this discrepancy are expected to be multifactorial, species differences are likely a key factor. Consequently, a human-based model is a desirable solution to this problem, which has been made possible by the advent of human induced pluripotent stem cells (iPSCs). In particular, recent advances in the field now allow the efficient generation of a variety of vascular cells (e.g., endothelial cells, smooth muscle cells, and pericytes) from iPSCs. Using these cells, different vascular models have been established, ranging from simple 2D cultures to highly sophisticated vascular organoids and microfluidic devices. Toxicity testing using these models can recapitulate key aspects of vascular pathology on molecular (e.g., secretion of proinflammatory cytokines), cellular (e.g., cell apoptosis), and in some cases, tissue (e.g., endothelium barrier dysfunction) levels. These encouraging data provide the rationale for continuing efforts in the exploration, optimization, and validation of the iPSC technology in vascular toxicology.

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.

Sign in / Sign up

Export Citation Format

Share Document