scholarly journals When CAR Meets Stem Cells

2019 ◽  
Vol 20 (8) ◽  
pp. 1825 ◽  
Author(s):  
Jung Min Lee

The generation of immune cells from human pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) has been of keen interest to regenerative medicine. Pluripotent stem cell-derived immune cells such as natural killer cells, macrophages, and lymphoid cells, especially T cells, can be used in immune cell therapy to treat incurable cancers. Moreover, since the advent of chimeric antigen receptor (CAR) technology, the success of CAR-T cells in the clinic has galvanized new efforts to harness the power of CAR technology to generate CAR-engineered immune cells from pluripotent stem cells. This review provides a summary of pluripotent stem cell-derived immune cells and CAR technology, together with perspectives on combining pluripotent stem-cell derived immune cells and CAR engineering to pave a new way for developing next generation immune cell therapy.

Author(s):  
Fariha Khaliq

Stem cell therapy is an approach to use cells that have the ability of self-renewal and to differentiate into different types of functional cells that are obtained from embryo and other postnatal sources to treat multiple disorders. These cells can be differentiated into different types of stem cells based on their specific characteristics to be totipotent, unipotent, multipotent or pluripotent. As potential therapy, pluripotent stem cells are considered to be the most interesting as they can be differentiated into different type of cells with similar characteristics as embryonic stem cells. Induced pluripotent stem cells (iPSCs) are adult cells that are reprogrammed genetically into stem cells from human fibroblasts through expressing genes and transcription factors at different time intervals. In this review, we will discuss the applications of stem cell therapy using iPSCs technology in treating neurodegenerative disorder such that Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS). We have also broadly highlighted the significance of pluripotent stem cells in stem cell therapy.


2020 ◽  
Vol 7 (2) ◽  
pp. 31
Author(s):  
Brian Lee ◽  
Breanna S. Borys ◽  
Michael S. Kallos ◽  
Carlos A. V. Rodrigues ◽  
Teresa P. Silva ◽  
...  

Allogeneic cell therapy products, such as therapeutic cells derived from pluripotent stem cells (PSCs), have amazing potential to treat a wide variety of diseases and vast numbers of patients globally. However, there are various challenges related to the manufacturing of PSCs in large enough quantities to meet commercial needs. This manuscript addresses the challenges for the process development of PSCs production in a bioreactor, and also presents a scalable bioreactor technology that can be a possible solution to remove the bottleneck for the large-scale manufacturing of high-quality therapeutic cells derived from PSCs.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Alessander Leyendecker Junior

Due to their potential for tissue engineering applications and ability to modulate the immune system and reduce inflammation, mesenchymal stem cells (MSCs) have been explored as a promising option for the treatment of chronic diseases and injuries. However, there are problems associated with the use of this type of cell that limit their applications. Several studies have been exploring the possibility to produce mesenchymal stem cells from pluripotent stem cells (PSCs). The aim of these studies is to generate MSCs with advantageous characteristics of both PSCs and MSCs. However, there are still some questions concerning the characteristics of MSCs derived from the differentiation of PSCs that must be answered before they can be used to treat diseases and injuries. The objective of this study was, therefore, to determine if PSCs exposed to SB431542, a TGF-β inhibitor, are able to differentiate to MSCs, judging by morphology, expression of mesenchymal and pluripotent stem cell markers, expression of pluripotency-related genes, and ability to differentiate to osteocytes and adipocytes. The results obtained demonstrated that it is possible to induce the differentiation of both embryonic stem cells and induce pluripotent stem cells into cells with characteristics that highly resemble those from MSCs through the inhibition of the TGF-β pathway.


2013 ◽  
Vol 25 (1) ◽  
pp. 294
Author(s):  
J.-K. Park ◽  
K.-H. Choi ◽  
D.-C. Son ◽  
J.-I. Oh ◽  
C.-K. Lee

A recent study has reported that pluripotent stem cells can be categorized according to their pluripotent state. The first is the “naïve” state, which is characterised by small, round or dome-shaped colony morphologies, LIF and BMP4 signalling pathways, and 2 active X chromosomes in females; mouse embryonic stem cells (mESC) represent this type. A second “primed” state has also been described and is possible in mouse epiblast stem cells (mEpiSC) or human embryonic stem cells (hESC). These primed state pluripotent stem cells display flattened monolayer colony morphologies, FGF and nodal/activin signalling pathways, and X chromosome inactivation in females. Meanwhile, a few studies have reported that primed pluripotent stem cell lines could be reverted to a naïve pluripotent state using various exogenous factors including GSK3β and MEK inhibitors (2i), LIF, hypoxic conditions, and upregulation of Oct3 or klf4. Therefore, the purpose of this study was to investigate whether a LIF-dependent naïve pluripotent stem cell line could be derived from porcine embryonic fibroblasts (PEF) via various previously reported factors. We were able to successfully induce PEF into a naïve state-like pluripotent stem cell line by viral infection using FUW-tetO-hOCT4, FUW-tetO-hSOX2, FUW-tetO-hKlf4, FUW-tetO-hMYC, and FUW-M2rtTA obtained from Addgene and addition of 2i and LIF. These naive state-like pluripotent stem cells display mESC-like morphologies, clonogenicity by trypsin, and expression of Oct4, Sox2, Nanog, and SSEA1 using PCR, immunocytochemistry, and fluorescence-activated cell sorting. All cell lines maintained stemness characteristics and stable morphology for more than 30 passages. In addition, naïve state-like pluripotent stem cells could be induced to differentiate to fibroblast-like cells by withdrawal of doxycycline, lif, and 2i. These differentiated cells could be regenerated into naïve state-like pluripotent stem cells by addition of doxycycline, lif, and 2i. We suggest that, as a nonpermissive species, the porcine species undergoes reprogramming into a primed state during the establishment of pluripotent stem cell lines and needs various exogenous factors, including continuous transgene expression, GSK3β and MEK inhibitors (2i), and LIF to be induced into naïve state-like pluripotent stem cells. This work was supported by the BioGreen 21 Program (PJ0081382011), Rural Development Administration, Republic of Korea.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fei Lu ◽  
Xiao-Jing-Nan Ma ◽  
Wei-Lin Jin ◽  
Yang Luo ◽  
Xun Li

Immunotherapy has become an indispensable part of the comprehensive treatment of hepatocellular carcinoma (HCC). Immunotherapy has proven effective in patients with early HCC, advanced HCC, or HCC recurrence after liver transplantation. Clinically, the most commonly used immunotherapy is immune checkpoint inhibition using monoclonal antibodies, such as CTLA-4 and PD-1. However, it cannot fundamentally solve the problems of a weakened immune system and inactivation of immune cells involved in killing tumor cells. T cells can express tumor antigen-recognizing T cell receptors (TCRs) or chimeric antigen receptors (CARs) on the cell surface through gene editing to improve the specificity and responsiveness of immune cells. According to previous studies, TCR-T cell therapy is significantly better than CAR-T cell therapy in the treatment of solid tumors and is one of the most promising immune cell therapies for solid tumors so far. However, its application in the treatment of HCC is still being researched. Technological advancements in induction and redifferentiation of induced pluripotent stem cells (iPSCs) allow us to use T cells to induce T cell-derived iPSCs (T-iPSCs) and then differentiate them into TCR-T cells. This has allowed a convenient strategy to study HCC models and explore optimal treatment strategies. This review gives an overview of the major advances in the development of protocols to generate neoantigen-specific TCR-T cells from T-iPSCs. We will also discuss their potential and challenges in the treatment of HCC.


1970 ◽  
Vol 1 (3) ◽  
pp. 22-34
Author(s):  
M Ullah ◽  
Vidyanath Chaudhary ◽  
Nurul Absar

The controversy surrounding stem cell research led to an intense debate about ethics. Up until the recent years, the research method mainly focused on Embryonic Stem Cells, which involves taking tissue from an aborted embryo to get proper material to study. This is typically done just days after conception or between the 5th and 9th week. Since then, researchers have moved on to more ethical study methods, such as Induced Pluripotent Stem Cells (iPS). iPS is artificially derived from a non-pluripotent cell, such as adult somatic cells. This is probably an important advancement in stem cell research, since it allows researchers to obtain pluripotent stem cells, which are important in research, without the controversial use of embryos. Nowadays stem cell treatment has been spreaded throughout the world. It has also been grown commercially in developed countries. This paper assesses the stem cell treatment as well as its impact in human life. It also examines specific stem cell therapy market that proves far reaching effect in world economy. Though various organizations have made it as a controversial issue the analysis shows that stem cell treatment has brought positive dimension in human society. A discussion has been made about the ethical issues of stem cell research and therapy; which focus how recent biotechnology and biological understandings of development narrow the debate. It is thought that one day it may be the major key to treat various diseases. DOI: http://dx.doi.org/10.3329/bioethics.v1i3.9631 Bangladesh Journal of Bioethics 2010; 1(3): 22-34


2015 ◽  
Vol 88 (3) ◽  
pp. 265-271 ◽  
Author(s):  
Mihai Girlovanu ◽  
Sergiu Susman ◽  
Olga Soritau ◽  
Dan Rus-Ciuca ◽  
Carmen Melincovici ◽  
...  

In recent years, the advances in stem cell research have suggested that the human body may have a higher plasticity than it was originally expected.Until now, four categories of stem cells were isolated and cultured in vivo: embryonic stem cells, fetal stem cells, adult stem cells and induced pluripotent stem cells (hiPSCs).Although multiple studies were published, several issues concerning the stem cells are still debated, such as: the molecular mechanisms of differentiation, the methods to prevent teratoma formation or the ethical and religious issues regarding especially the embryonic stem cell research.The direct differentiation of stem cells into specialized cells: cardiac myocytes, neural cells, pancreatic islets cells, may represent an option in treating incurable diseases such as: neurodegenerative diseases, type I diabetes, hematologic or cardiac diseases.Nevertheless, stem cell-based therapies, based on stem cell transplantation, remain mainly at the experimental stages and their major limitation is the development of teratoma and cancer after transplantation. The induced pluripotent stem cells (hiPSCs) represent a prime candidate for future cell therapy research because of their significant self-renewal and differentiation potential and the lack of ethical issues.This article presents an overview of the biological advances in the study of stem cells and the current progress made in the field of regenerative medicine.


2021 ◽  
Vol 22 (9) ◽  
pp. 5011
Author(s):  
Daehwan Kim ◽  
Sangho Roh

Stem cell research is essential not only for the research and treatment of human diseases, but also for the genetic preservation and improvement of animals. Since embryonic stem cells (ESCs) were established in mice, substantial efforts have been made to establish true ESCs in many species. Although various culture conditions were used to establish ESCs in cattle, the capturing of true bovine ESCs (bESCs) has not been achieved. In this review, the difficulty of establishing bESCs with various culture conditions is described, and the characteristics of proprietary induced pluripotent stem cells and extended pluripotent stem cells are introduced. We conclude with a suggestion of a strategy for establishing true bESCs.


Author(s):  
Anja Trillhaase ◽  
Marlon Maertens ◽  
Zouhair Aherrahrou ◽  
Jeanette Erdmann

AbstractStem cell technology has been around for almost 30 years and in that time has grown into an enormous field. The stem cell technique progressed from the first successful isolation of mammalian embryonic stem cells (ESCs) in the 1990s, to the production of human induced-pluripotent stem cells (iPSCs) in the early 2000s, to finally culminate in the differentiation of pluripotent cells into highly specialized cell types, such as neurons, endothelial cells (ECs), cardiomyocytes, fibroblasts, and lung and intestinal cells, in the last decades. In recent times, we have attained a new height in stem cell research whereby we can produce 3D organoids derived from stem cells that more accurately mimic the in vivo environment. This review summarizes the development of stem cell research in the context of vascular research ranging from differentiation techniques of ECs and smooth muscle cells (SMCs) to the generation of vascularized 3D organoids. Furthermore, the different techniques are critically reviewed, and future applications of current 3D models are reported. Graphical abstract


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