scholarly journals Selected small molecules as inductors of pluripotent stem cells

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Małgorzata Baranek ◽  
Wojciech T Markiewicz ◽  
Jan Barciszewski

The general idea of regenerative medicine is to fix or replace tissues or organs with alive and patient-specific implants. Pluripotent stem cells are capable of indefinite self-renewal and differentiation into all cell types of body with origin from the three germ layers of the developing embryo, therefore they have a potential to play a substantial role in regenerative medicine. Easily accessible source of induced pluripotent stem cells may allow obtaining and culturing tissues in vitro. Many improvements in the methods leading to obtain such cells have been made by various research groups in order to limit immunogenicity and tumorigenesis, increase efficiency and accelerate kinetics. One of the approaches affecting pluripotency is usage of small molecule compounds including RNA-derivatives – nucleosides analogues. It would be great to assess general character of such molecules and reveal their new derivatives or modifications to improve induced pluripotent stem cells (iPSCs) reprogramming efficiency. Understanding the epigenetic changes during cellular reprogramming will extend understanding of stem cell biology and lead to potential therapeutic approaches. In this digest of compounds found in literature as proven or putative inductors of cells’ reprogramming to pluripotency there are compounds that may substitute for transgenic nucleic acids delivery in order to improve time and efficiency of reprogramming. Nucleic acids’ derivatives or modifications of particular atoms or substitutes influence modulating activities of small molecules, especially their inhibiting activity.  Due to dosage-dependent effect of small molecules influence on genes, their application concentration needs to be strictly determined.

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Ryan O'Doherty ◽  
Udo Greiser ◽  
Wenxin Wang

The concept of inducing pluripotency to adult somatic cells by introducing reprogramming factors to them is one that has recently emerged, gained widespread acclaim and garnered much attention among the scientific community. The idea that cells can be reprogrammed, and are not unidirectionally defined opens many avenues for study. With their clear potential for use in the clinic, these reprogrammed cells stand to have a huge impact in regenerative medicine. This realization did not occur overnight but is, however, the product of many decades worth of advancements in researching this area. It was a combination of such research that led to the development of induced pluripotent stem cells as we know it today. This review delivers a brief insight in to the roots of iPS research and focuses on succinctly describing current nonviral methods of inducing pluripotency using plasmid vectors, small molecules and chemicals, and RNAs.


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Sally K. Mak ◽  
Y. Anne Huang ◽  
Shifteh Iranmanesh ◽  
Malini Vangipuram ◽  
Ramya Sundararajan ◽  
...  

Efficientin vitrodifferentiation into specific cell types is more important than ever after the breakthrough in nuclear reprogramming of somatic cells and its potential for disease modeling and drug screening. Key success factors for neuronal differentiation are the yield of desired neuronal marker expression, reproducibility, length, and cost. Three main neuronal differentiation approaches are stromal-induced neuronal differentiation, embryoid body (EB) differentiation, and direct neuronal differentiation. Here, we describe our neurodifferentiation protocol using small molecules that very efficiently promote neural induction in a 5-stage EB protocol from six induced pluripotent stem cells (iPSC) lines from patients with Parkinson’s disease and controls. This protocol generates neural precursors using Dorsomorphin and SB431542 and further maturation into dopaminergic neurons by replacing sonic hedgehog with purmorphamine or smoothened agonist. The advantage of this approach is that all patient-specific iPSC lines tested in this study were successfully and consistently coaxed into the neural lineage.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Tongxiang Lin ◽  
Shouhai Wu

Induced pluripotent stem cells (iPSCs) could be employed in the creation of patient-specific stem cells, which could subsequently be used in various basic and clinical applications. However, current iPSC methodologies present significant hidden risks with respect to genetic mutations and abnormal expression which are a barrier in realizing the full potential of iPSCs. A chemical approach is thought to be a promising strategy for safety and efficiency of iPSC generation. Many small molecules have been identified that can be used in place of exogenous transcription factors and significantly improve iPSC reprogramming efficiency and quality. Recent studies have shown that the use of small molecules results in the generation of chemically induced pluripotent stem cells from mouse embryonic fibroblast cells. These studies might lead to new areas of stem cell research and medical applications, not only human iPSC by chemicals alone, but also safe generation of somatic stem cells for cell based clinical trials and other researches. In this paper, we have reviewed the recent advances in small molecule approaches for the generation of iPSCs.


2020 ◽  
Vol 15 (3) ◽  
pp. 233-242 ◽  
Author(s):  
Yunchang Zhao ◽  
Honghao Liu ◽  
Chunjie Zhao ◽  
Peng Dang ◽  
Haijian Li ◽  
...  

Osteoarthritis (OA), as a degenerative joint disease, is the most common form of joint disorder that causes pain, stiffness, and other symptoms associated with OA. Various genetic, biomechanical, and environmental factors have a relevant role in the development of OA. To date, extensive efforts are currently being made to overcome the poor self-healing capacity of articular cartilage. Despite the pivotal role of chondrocytes, their proliferation and repair capacity after tissue injury are limited. Therefore, the development of new strategies to overcome these constraints is urgently needed. Recent advances in regenerative medicine suggest that pluripotent stem cells are promising stem cell sources for cartilage repair. Pluripotent stem cells are undifferentiated cells that have the capacity to differentiate into different types of cells and can self-renew indefinitely. In the past few decades, numerous attempts have been made to regenerate articular cartilage by using induced pluripotent stem cells (iPSCs). The potential applications of patient-specific iPSCs hold great promise for regenerative medicine and OA treatment. However, there are different culture conditions for the preparation and characterization of human iPSCs-derived chondrocytes (hiChondrocytes). Recent biochemical analyses reported that several paracrine factors such as TGFb, BMPs, WNT, Ihh, and Runx have been shown to be involved in cartilage cell proliferation and differentiation from human iPSCs. In this review, we summarize and discuss the paracrine interactions involved in human iPSCs differentiation into chondrocytes in different cell culture media.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Yuehong Wu ◽  
Anuja Mishra ◽  
Zhifang Qiu ◽  
Steven Farnsworth ◽  
Suzette D. Tardif ◽  
...  

Among the various species from which induced pluripotent stem cells have been derived, nonhuman primates (NHPs) have a unique role as preclinical models. Their relatedness to humans and similar physiology, including central nervous system, make them ideal for translational studies. We review here the progress made in deriving and characterizing iPS cell lines from different NHP species. We focus on iPS cell lines from the marmoset, a small NHP in which several human disease states can be modeled. The marmoset can serve as a model for the implementation of patient-specific autologous cell therapy in regenerative medicine.


2021 ◽  
Vol 7 (12) ◽  
pp. eabf7412
Author(s):  
P. Nayak ◽  
A. Colas ◽  
M. Mercola ◽  
S. Varghese ◽  
S. Subramaniam

Understanding the mechanisms of myogenesis in human induced pluripotent stem cells (hiPSCs) is a prerequisite to achieving patient-specific therapy for diseases of skeletal muscle. hiPSCs of different origin show distinctive kinetics and ability to differentiate into myocytes. To address the unique cellular and temporal context of hiPSC differentiation, we perform a longitudinal comparison of the transcriptomic profiles of three hiPSC lines that display differential myogenic specification, one robust and two blunted. We detail temporal differences in mechanisms that lead to robust myogenic specification. We show gene expression signatures of putative cell subpopulations and extracellular matrix components that may support myogenesis. Furthermore, we show that targeted knockdown of ZIC3 at the outset of differentiation leads to improved myogenic specification in blunted hiPSC lines. Our study suggests that β-catenin transcriptional cofactors mediate cross-talk between multiple cellular processes and exogenous cues to facilitate specification of hiPSCs to mesoderm lineage, leading to robust myogenesis.


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