Paracrine Interactions Involved in Human Induced Pluripotent Stem Cells Differentiation into Chondrocytes

2020 ◽  
Vol 15 (3) ◽  
pp. 233-242 ◽  
Author(s):  
Yunchang Zhao ◽  
Honghao Liu ◽  
Chunjie Zhao ◽  
Peng Dang ◽  
Haijian Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Great Promise ◽  
Paracrine Factors ◽  
Human Ipscs ◽  
Induced Pluripotent

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.

scholarly journals Derivation of induced pluripotent stem cells from ferret somatic cells

2020 ◽  
Vol 318 (4) ◽  
pp. L671-L683
Author(s):  
Jinghui Gao ◽  
Sophia Petraki ◽  
Xingshen Sun ◽  
Leonard A. Brooks ◽  
Thomas J. Lynch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Preclinical Model ◽  
Specific Cell ◽  
Chronic Lung Diseases ◽  
Human Ipscs ◽  
Fetal Fibroblasts ◽  
Induced Pluripotent

Ferrets are an attractive mammalian model for several diseases, especially those affecting the lungs, liver, brain, and kidneys. Many chronic human diseases have been difficult to model in rodents due to differences in size and cellular anatomy. This is particularly the case for the lung, where ferrets provide an attractive mammalian model of both acute and chronic lung diseases, such as influenza, cystic fibrosis, A1A emphysema, and obliterative bronchiolitis, closely recapitulating disease pathogenesis, as it occurs in humans. As such, ferrets have the potential to be a valuable preclinical model for the evaluation of cell-based therapies for lung regeneration and, likely, for other tissues. Induced pluripotent stem cells (iPSCs) provide a great option for provision of enough autologous cells to make patient-specific cell therapies a reality. Unfortunately, they have not been successfully created from ferrets. In this study, we demonstrate the generation of ferret iPSCs that reflect the primed pluripotent state of human iPSCs. Ferret fetal fibroblasts were reprogrammed and acquired core features of pluripotency, having the capacity for self-renewal, multilineage differentiation, and a high-level expression of the core pluripotency genes and pathways at both the transcriptional and protein level. In conclusion, we have generated ferret pluripotent stem cells that provide an opportunity for advancing our capacity to evaluate autologous cell engraftment in ferrets.

Clinical Application of Induced Pluripotent Stem Cells in Cardiovascular Medicine

Cardiology ◽  
2015 ◽  
Vol 131 (4) ◽  
pp. 236-244 ◽  
Author(s):  
Hong-jie Chi ◽  
Song Gao ◽  
Xin-chun Yang ◽  
Jun Cai ◽  
Wen-shu Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Clinical Application ◽  
Drug Screening ◽  
Pluripotent Stem Cells ◽  
Disease Diagnosis ◽  
The Body ◽  
Patient Specific ◽  
Human Ipscs ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) are generated by reprogramming human somatic cells through the overexpression of four transcription factors: Oct4, Sox2, Klf4 and c-Myc. iPSCs are capable of indefinite self-renewal, and they can differentiate into almost any type of cell in the body. These cells therefore offer a highly valuable therapeutic strategy for tissue repair and regeneration. Recent experimental and preclinical research has revealed their potential for cardiovascular disease diagnosis, drug screening and cellular replacement therapy. Nevertheless, significant challenges remain in terms of the development and clinical application of human iPSCs. Here, we review current progress in research related to patient-specific iPSCs for ex vivo modeling of cardiovascular disorders and drug screening, and explore the potential of human iPSCs for use in the field of cardiovascular regenerative medicine.

scholarly journals Hepatocyte-like cells derived from human induced pluripotent stem cells using small molecules: implications of a transcriptomic study

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiugong Gao ◽  
Rong Li ◽  
Patrick Cahan ◽  
Yang Zhao ◽  
Jeffrey J. Yourick ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Molecules ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Liver Tissue ◽  
Transcriptomic Analysis ◽  
Great Promise ◽  
Hepatocyte Differentiation ◽  
Human Ipscs ◽  
Induced Pluripotent

Abstract Background Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs) hold great promise in toxicological applications as well as in regenerative medicine. Previous efforts on hepatocyte differentiation have mostly relied on the use of growth factors (GFs) to recapitulate developmental signals under in vitro conditions. Recently, the use of small molecules (SMs) has emerged as an attractive tool to induce cell fate transition due to its superiority in terms of both quality and cost. However, HLCs derived using SMs have not been well characterized, especially on the transcriptome level. Methods HLCs were differentiated from human iPSCs using a protocol that only involves SMs and characterized by transcriptomic analysis using whole genome microarrays. Results HLCs derived using the SM protocol (HLC_SM) displayed specific hepatic marker expression and demonstrated key hepatic functions. Transcriptomic analysis of the SM-driven differentiation defined a hepatocyte differentiation track and characterized the expression of some key marker genes in major stages of hepatocyte differentiation. In addition, HLC_SM were scored with CellNet, a bioinformatics tool quantifying how closely engineered cell populations resemble their target cell type, and compared to primary human hepatocytes (PHHs), adult liver tissue, fetal liver tissue, HLCs differentiated using GFs (HLC_GF), and commercially available HLCs. Similar to HLC_GF, HLC_SM displayed a mixed phenotype of fetal and adult hepatocytes and had relatively low expression of metabolic enzymes, transporters, and nuclear receptors compared to PHHs. Finally, the differentially expressed genes in HLC_SM compared to HLC_GF and to PHHs were analyzed to identify pathways and upstream transcription regulators which could potentially be manipulated to improve the differentiation of HLCs. Conclusions Overall, the present study demonstrated the usefulness of the SM-based hepatocyte differentiation method, offered new insights into the molecular basis of hepatogenesis and associated gene regulation, and suggested ways for further improvements in hepatocyte differentiation in order to obtain more mature HLCs that could be used in toxicological studies.

scholarly journals Induced Pluripotent Stem Cells as a Tool for Modeling Hematologic Disorders and as a Potential Source for Cell-Based Therapies

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3250
Author(s):  
Ponthip Pratumkaew ◽  
Surapol Issaragrisil ◽  
Sudjit Luanpitpong
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Drug Screening ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Patient Specific ◽  
Great Promise ◽  
Hematologic Disorders ◽  
Cell Based Therapy ◽  
Induced Pluripotent

The breakthrough in human induced pluripotent stem cells (hiPSCs) has revolutionized the field of biomedical and pharmaceutical research and opened up vast opportunities for drug discovery and regenerative medicine, especially when combined with gene-editing technology. Numerous healthy and patient-derived hiPSCs for human disease modeling have been established, enabling mechanistic studies of pathogenesis, platforms for preclinical drug screening, and the development of novel therapeutic targets/approaches. Additionally, hiPSCs hold great promise for cell-based therapy, serving as an attractive cell source for generating stem/progenitor cells or functional differentiated cells for degenerative diseases, due to their unlimited proliferative capacity, pluripotency, and ethical acceptability. In this review, we provide an overview of hiPSCs and their utility in the study of hematologic disorders through hematopoietic differentiation. We highlight recent hereditary and acquired genetic hematologic disease modeling with patient-specific iPSCs, and discuss their applications as instrumental drug screening tools. The clinical applications of hiPSCs in cell-based therapy, including the next-generation cancer immunotherapy, are provided. Lastly, we discuss the current challenges that need to be addressed to fulfill the validity of hiPSC-based disease modeling and future perspectives of hiPSCs in the field of hematology.

scholarly journals Selected small molecules as inductors of pluripotent stem cells

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Małgorzata Baranek ◽  
Wojciech T Markiewicz ◽  
Jan Barciszewski
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Nucleic Acids ◽  
Small Molecules ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
General Idea ◽  
Patient Specific ◽  
General Character ◽  
Induced Pluripotent

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.

scholarly journals Nonhuman Primate Induced Pluripotent Stem Cells in Regenerative Medicine

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Yuehong Wu ◽  
Anuja Mishra ◽  
Zhifang Qiu ◽  
Steven Farnsworth ◽  
Suzette D. Tardif ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Cell Lines ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Ips Cell ◽  
Disease States ◽  
Autologous Cell Therapy ◽  
Induced Pluripotent

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.

scholarly journals Recent Updates on Induced Pluripotent Stem Cells in Hematological Disorders

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Methichit Wattanapanitch
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Genome Editing ◽  
Drug Screening ◽  
Pluripotent Stem Cells ◽  
The Body ◽  
Patient Specific ◽  
Hematological Disorders ◽  
Human Ipscs ◽  
Induced Pluripotent

Over the past decade, enormous progress has been made in the field of induced pluripotent stem cells (iPSCs). Patients’ somatic cells such as skin fibroblasts or blood cells can be used to generate disease-specific pluripotent stem cells, which have unlimited proliferation and can differentiate into all cell types of the body. Human iPSCs offer great promises and opportunities for treatments of degenerative diseases and studying disease pathology and drug screening. So far, many iPSC-derived disease models have led to the discovery of novel pathological mechanisms as well as new drugs in the pipeline that have been tested in the iPSC-derived cells for efficacy and potential toxicities. Furthermore, recent advances in genome editing technology in combination with the iPSC technology have provided a versatile platform for studying stem cell biology and regenerative medicine. In this review, an overview of iPSCs, patient-specific iPSCs for disease modeling and drug screening, applications of iPSCs and genome editing technology in hematological disorders, remaining challenges, and future perspectives of iPSCs in hematological diseases will be discussed.

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