scholarly journals Cell-Based Therapeutic Approaches for Cystic Fibrosis

2020 ◽  
Vol 21 (15) ◽  
pp. 5219
Author(s):  
Pascal Duchesneau ◽  
Thomas K. Waddell ◽  
Golnaz Karoubi
Keyword(s):  
Cystic Fibrosis ◽  
Cell Therapy ◽  
Treatment Method ◽  
Transmembrane Conductance Regulator ◽  
Therapeutic Approaches ◽  
Ips Cell ◽  
Multiple Organs ◽  
Current State ◽  
Cell Sources ◽  
Induced Pluripotent

Cystic Fibrosis (CF) is a chronic autosomal recessive disease caused by defects in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Cystic Fibrosis affects multiple organs but progressive remodeling of the airways, mucus accumulation, and chronic inflammation in the lung, result in lung disease as the major cause of morbidity and mortality. While advances in management of CF symptoms have increased the life expectancy of this devastating disease, and there is tremendous excitement about the potential of new agents targeting the CFTR molecule itself, there is still no curative treatment. With the recent advances in the identification of endogenous airway progenitor cells and in directed differentiation of pluripotent cell sources, cell-based therapeutic approaches for CF have become a plausible treatment method with the potential to ultimately cure the disease. In this review, we highlight the current state of cell therapy in the CF field focusing on the relevant autologous and allogeneic cell populations under investigation and the challenges associated with their use. In addition, we present advances in induced pluripotent stem (iPS) cell approaches and emerging new genetic engineering methods, which have the capacity to overcome the current limitations hindering cell therapy approaches.

scholarly journals Progress in precision medicine in cystic fibrosis: a focus on CFTR modulator therapy

Breathe ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. 210112
Author(s):  
Daniel H. Tewkesbury ◽  
Rebecca C. Robey ◽  
Peter J. Barry
Keyword(s):  
Cystic Fibrosis ◽  
Precision Medicine ◽  
Real World ◽  
Chloride Ion ◽  
Transmembrane Conductance Regulator ◽  
Therapeutic Approaches ◽  
Transmembrane Conductance ◽  
Cftr Protein ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators

The genetic multisystem condition cystic fibrosis (CF) has seen a paradigm shift in therapeutic approaches within the past decade. Since the first clinical descriptions in the 1930s, treatment advances had focused on the downstream consequences of a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion channel. The discovery of the gene that codes for CFTR and an understanding of the way in which different genetic mutations lead to disruption of normal CFTR function have led to the creation and subsequent licensing of drugs that target this process. This marks an important move towards precision medicine in CF and results from clinical trials and real-world clinical practice have been impressive. In this review we outline how CFTR modulator drugs restore function to the CFTR protein and the progress that is being made in this field. We also describe the real-world impact of CFTR modulators on both pulmonary and multisystem complications of CF and what this will mean for the future of CF care.

scholarly journals Incidental Finding of a Homozygous p.M348K Asymptomatic Italian Patient Confirms the Many Faces of Cystic Fibrosis

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Rossana Molinario ◽  
Sara Palumbo ◽  
Paola Concolino ◽  
Sandro Rocchetti ◽  
Roberta Rizza ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Incidental Finding ◽  
Pancreatic Insufficiency ◽  
Normal Male ◽  
Transmembrane Conductance Regulator ◽  
Coding Region ◽  
Multiple Organs ◽  
Rare Polymorphism ◽  
The Many ◽  
Next Generation Sequencing Ngs

Cystic fibrosis (CF; OMIM number 219700) is an autosomal recessive disease caused by mutations in theCFTR(cystic fibrosis transmembrane conductance regulator) gene, which results in abnormal viscous mucoid secretions in multiple organs and whose main clinical features are pancreatic insufficiency, chronic endobronchial infection, and male infertility. We report the case of a 47-year-old apparently normal male resulting in homozygosity for the mutation p.M348K from nonconsanguineous parents. The proband was screened using a standard panel of 70 different tested on NanoChip 400 platform. The massive parallel pyrosequencing on 454 JS machine allowed the second level analysis. The patient was firstly screened with two different platforms available in our laboratory, obtaining an ambiguous signal for the p.R347P mutation. For this reason we decided to clarify the discordant result ofCFTRstatus by Next Generation Sequencing (NGS) using 454 Junior instrument. The patient is resulted no carrier of the p.R347P mutation, but NGS highlighted a homozygous substitution from T>A at position 1043 in the coding region, causing an amino acid substitution from methionine to lysine (p.M348K). Casual finding of p.M348K homozygote mutation in an individual, without any feature of classical or nonclassical CF form, allowed us to confirm that p.M348K is a benign rare polymorphism.

scholarly journals Extracellular Matrix-Dependent Generation of Integration- and Xeno-Free iPS Cells Using a Modified mRNA Transfection Method

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kang-In Lee ◽  
Seo-Young Lee ◽  
Dong-Youn Hwang
Keyword(s):  
Extracellular Matrix ◽  
Cell Therapy ◽  
Culture System ◽  
Ips Cells ◽  
Great Promise ◽  
Ips Cell ◽  
Transfection Method ◽  
Reprogramming Efficiency ◽  
Mrna Transfection ◽  
Induced Pluripotent

Human induced pluripotent stem cells (iPS cells) hold great promise in the field of regenerative medicine, especially immune-compatible cell therapy. The most important safety-related issues that must be resolved before the clinical use of iPS cells include the generation of “footprint-free” and “xeno-free” iPS cells. In this study, we sought to examine whether an extracellular matrix- (ECM-) based xeno-free culture system that we recently established could be used together with a microRNA-enhanced mRNA reprogramming method for the generation of clinically safe iPS cells. The notable features of this method are the use of a xeno-free/feeder-free culture system for the generation and expansion of iPS cells rather than the conventional labor-intensive culture systems using human feeder cells or human feeder-conditioned medium and the enhancement of mRNA-mediated reprogramming via the delivery of microRNAs. Strikingly, we observed the early appearance of iPS cell colonies (~11 days), substantial reprogramming efficiency (~0.2–0.3%), and a high percentage of ESC-like colonies among the total colonies (~87.5%), indicating enhanced kinetics and reprogramming efficiency. Therefore, the combined method established in this study provides a valuable platform for the generation and expansion of clinically safe (i.e., integration- and xeno-free) iPS cells, facilitating immune-matched cell therapy in the near future.

scholarly journals Cell Reprogramming, IPS Limitations, and Overcoming Strategies in Dental Bioengineering

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Gaskon Ibarretxe ◽  
Antonia Alvarez ◽  
Maria-Luz Cañavate ◽  
Enrique Hilario ◽  
Maitane Aurrekoetxea ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Ips Cells ◽  
Cell Reprogramming ◽  
Animal Cells ◽  
Ips Cell ◽  
Current State ◽  
Organ Systems ◽  
Induced Pluripotent ◽  
Long Term Behavior

The procurement of induced pluripotent stem cells, or IPS cells, from adult differentiated animal cells has the potential to revolutionize future medicine, where reprogrammed IPS cells may be used to repair disease-affected tissues on demand. The potential of IPS cell technology is tremendous, but it will be essential to improve the methodologies for IPS cell generation and to precisely evaluate each clone and subclone of IPS cells for their safety and efficacy. Additionally, the current state of knowledge on IPS cells advises that research on their regenerative properties is carried out in appropriate tissue and organ systems that permit a safe assessment of the long-term behavior of these reprogrammed cells. In the present paper, we discuss the mechanisms of cell reprogramming, current technical limitations of IPS cells for their use in human tissue engineering, and possibilities to overcome them in the particular case of dental regeneration.

scholarly journals Immunotherapy with 4-1BBL-Expressing iPS Cell‐Derived Myeloid Lines Amplifies Antigen-Specific T Cell Infiltration in Advanced Melanoma

2021 ◽  
Vol 22 (4) ◽  
pp. 1958
Author(s):  
Haruka Kuriyama ◽  
Satoshi Fukushima ◽  
Toshihiro Kimura ◽  
Hisashi Kanemaru ◽  
Azusa Miyashita ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
Immune Cell ◽  
Induced Pluripotent Stem Cell ◽  
Epitope Peptide ◽  
Ips Cell ◽  
Surface Molecules ◽  
T Cell Infiltration ◽  
Tumor Tissues ◽  
Induced Pluripotent

We have established an immune cell therapy with immortalized induced pluripotent stem-cell–derived myeloid lines (iPS-ML). The benefits of using iPS-ML are the infinite proliferative capacity and ease of genetic modification. In this study, we introduced 4-1BBL gene to iPS-ML (iPS-ML-41BBL). The analysis of the cell-surface molecules showed that the expression of CD86 was upregulated in iPS-ML-41BBL more than that in control iPS-ML. Cytokine array analysis was performed using supernatants of the spleen cells that were cocultured with iPS-ML or iPS-ML-41BBL. Multiple cytokines that are beneficial to cancer immunotherapy were upregulated. Peritoneal injections of iPS-ML-41BBL inhibited tumor growth of peritoneally disseminated mouse melanoma and prolonged survival of mice compared to that of iPS-ML. Furthermore, the numbers of antigen-specific CD8+ T cells were significantly increased in the spleen and tumor tissues treated with epitope peptide-pulsed iPS-ML-41BBL compared to those treated with control iPS-ML. The number of CXCR6-positive T cells were increased in the tumor tissues after treatment with iPS-ML-41BBL compared to that with control iPS-ML. These results suggest that iPS-ML-41BBL could activate antigen-specific T cells and promote their infiltration into the tumor tissues. Thus, iPS-ML-41BBL may be a candidate for future immune cell therapy aiming to change immunological “cold tumor” to “hot tumor”.

Cell therapy for GI motility disorders: comparison of cell sources and proposed steps for treating Hirschsprung disease

2017 ◽  
Vol 312 (4) ◽  
pp. G348-G354 ◽  
Author(s):  
Lincon A. Stamp
Keyword(s):  
Cell Therapy ◽  
Pluripotent Stem Cells ◽  
Disease Model ◽  
Hirschsprung Disease ◽  
Neural Progenitors ◽  
Therapeutic Approaches ◽  
Cell Sources ◽  
Model Mouse ◽  
A Cell ◽  
Key Steps

Cell therapeutic approaches to treat a range of congenital and degenerative neuropathies are under intense investigation. There have been recent significant advancements in the development of cell therapy to treat disorders of the enteric nervous system (ENS), enteric neuropathies. These advances include the efficient generation of enteric neural progenitors from pluripotent stem cells and the rescue of a Hirschsprung disease model mouse following their transplantation into the bowel. Furthermore, a recent study provides evidence of functional innervation of the bowel muscle by neurons derived from transplanted ENS-derived neural progenitors. This mini-review discusses these recent findings, compares endogenous ENS-derived progenitors and pluripotent stem cell-derived progenitors as a cell source for therapy, and proposes the key steps for cell therapy to treat Hirschsprung disease.

scholarly journals Feeder-free differentiation and expansion for T cells from induced pluripotent stem cells

2021 ◽  
Author(s):  
Shoichi Iriguchi ◽  
Yutaka Yasui ◽  
Yohei Kawai ◽  
Suguru Arima ◽  
Mihoko Kunitomo ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
T Cell Therapy ◽  
Cell Sources ◽  
Induced Pluripotent ◽  
Further Development

Abstract Clinical efficacy demonstrated by chimeric antigen receptor T cell therapy call for further development that could broaden their applicability. One such direction is to develop alternate T-cell sources and T cells differentiated from pluripotent stem cells may be an ideal candidate.The present protocol provides a feeder-free and scalable method to generate T lymphocytes from induced pluripotent stem cells.

scholarly journals Current State-of-the-Art and Unresolved Problems in Using Human Induced Pluripotent Stem Cell-Derived Dopamine Neurons for Parkinson’s Disease Drug Development

2021 ◽  
Vol 22 (7) ◽  
pp. 3381
Author(s):  
S. A. Antonov ◽  
E. V. Novosadova
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Development ◽  
3D Culture ◽  
Ips Cells ◽  
Dopamine Neurons ◽  
Future Research ◽  
Ips Cell ◽  
Current State ◽  
Induced Pluripotent

Human induced pluripotent stem (iPS) cells have the potential to give rise to a new era in Parkinson’s disease (PD) research. As a unique source of midbrain dopaminergic (DA) neurons, iPS cells provide unparalleled capabilities for investigating the pathogenesis of PD, the development of novel anti-parkinsonian drugs, and personalized therapy design. Significant progress in developmental biology of midbrain DA neurons laid the foundation for their efficient derivation from iPS cells. The introduction of 3D culture methods to mimic the brain microenvironment further expanded the vast opportunities of iPS cell-based research of the neurodegenerative diseases. However, while the benefits for basic and applied studies provided by iPS cells receive widespread coverage in the current literature, the drawbacks of this model in its current state, and in particular, the aspects of differentiation protocols requiring further refinement are commonly overlooked. This review summarizes the recent data on general and subtype-specific features of midbrain DA neurons and their development. Here, we review the current protocols for derivation of DA neurons from human iPS cells and outline their general weak spots. The associated gaps in the contemporary knowledge are considered and the possible directions for future research that may assist in improving the differentiation conditions and increase the efficiency of using iPS cell-derived neurons for PD drug development are discussed.

scholarly journals Induced pluripotent stem cells for modelling human diseases

2011 ◽  
Vol 366 (1575) ◽  
pp. 2274-2285 ◽  
Author(s):  
Juli J. Unternaehrer ◽  
George Q. Daley
Keyword(s):  
Petri Dish ◽  
Ips Cells ◽  
Human Diseases ◽  
Directed Differentiation ◽  
Ips Cell ◽  
Current State ◽  
Metabolic Conditions ◽  
Cardiovascular Pathologies ◽  
Induced Pluripotent

Research into the pathophysiological mechanisms of human disease and the development of targeted therapies have been hindered by a lack of predictive disease models that can be experimentally manipulated in vitro . This review describes the current state of modelling human diseases with the use of human induced pluripotent stem (iPS) cell lines. To date, a variety of neurodegenerative diseases, haematopoietic disorders, metabolic conditions and cardiovascular pathologies have been captured in a Petri dish through reprogramming of patient cells into iPS cells followed by directed differentiation of disease-relevant cells and tissues. However, realizing the true promise of iPS cells for advancing our basic understanding of disease and ultimately providing novel cell-based therapies will require more refined protocols for generating the highly specialized cells affected by disease, coupled with strategies for drug discovery and cell transplantation.

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