scholarly journals iPSC-Derived Organoids as Therapeutic Models in Regenerative Medicine and Oncology

2021 ◽  
Vol 8 ◽  
Author(s):  
Ali G. Turhan ◽  
Jinwook W. Hwang ◽  
Diana Chaker ◽  
Albert Tasteyre ◽  
Theodoros Latsis ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Cell Biology ◽  
Gene Editing ◽  
Medicinal Products ◽  
Therapeutic Tool ◽  
Hereditary Cancers ◽  
Oncogenic Mutations ◽  
Organ Repair ◽  
Induced Pluripotent ◽  
Genomic Editing

Progress made during the last decade in stem cell biology allows currently an unprecedented potential to translate these advances into the clinical applications and to shape the future of regenerative medicine. Organoid technology is amongst these major developments, derived from primary tissues or more recently, from induced pluripotent stem cells (iPSC). The use of iPSC technology offers the possibility of cancer modeling especially in hereditary cancers with germline oncogenic mutations. Similarly, it has the advantage to be amenable to genome editing with introduction of specific oncogenic alterations using CRISPR-mediated gene editing. In the field of regenerative medicine, iPSC-derived organoids hold promise for the generation of future advanced therapeutic medicinal products (ATMP) for organ repair. Finally, it appears that they can be of highly useful experimental tools to determine cell targets of SARS-Cov-2 infections allowing to test anti-Covid drugs. Thus, with the possibilities of genomic editing and the development of new protocols for differentiation toward functional tissues, it is expected that iPSC-derived organoid technology will represent also a therapeutic tool in all areas of medicine.

scholarly journals Future perspective of induced pluripotent stem cells for diagnosis, drug screening and treatment of human diseases

2010 ◽  
Vol 104 (07) ◽  
pp. 39-44 ◽  
Author(s):  
Qizhou Lian ◽  
Yenyen Chow ◽  
Miguel Esteban ◽  
Duanqing Pei ◽  
Hung-Fat Tse
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Ips Cell ◽  
Cell Technology ◽  
Induced Pluripotent

SummaryRecent advances in stem cell biology have transformed the understanding of cell physiology and developmental biology such that it can now play a more prominent role in the clinical application of stem cell and regenerative medicine. Success in the generation of human induced pluripotent stem cells (iPS) as well as related emerging technology on the iPS platform provide great promise in the development of regenerative medicine. Human iPS cells show almost identical properties to human embryonic stem cells (ESC) in pluripotency, but avoid many of their limitations of use. In addition, investigations into reprogramming of somatic cells to pluripotent stem cells facilitate a deeper understanding of human stem cell biology. The iPS cell technology has offered a unique platform for studying the pathogenesis of human disease, pharmacological and toxicological testing, and cell-based therapy. Nevertheless, significant challenges remain to be overcome before the promise of human iPS cell technology can be realised.

scholarly journals Induced Pluripotent Stem Cells (iPSCs) and Gene Therapy: A New Era for the Treatment of Neurological Diseases

2021 ◽  
Vol 22 (24) ◽  
pp. 13674
Author(s):  
Giulia Paolini Sguazzi ◽  
Valentina Muto ◽  
Marco Tartaglia ◽  
Enrico Bertini ◽  
Claudia Compagnucci
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Recent Progress ◽  
Gene Editing ◽  
New Era ◽  
Induced Pluripotent

To date, gene therapy has employed viral vectors to deliver therapeutic genes. However, recent progress in molecular and cell biology has revolutionized the field of stem cells and gene therapy. A few years ago, clinical trials started using stem cell replacement therapy, and the induced pluripotent stem cells (iPSCs) technology combined with CRISPR-Cas9 gene editing has launched a new era in gene therapy for the treatment of neurological disorders. Here, we summarize the latest findings in this research field and discuss their clinical applications, emphasizing the relevance of recent studies in the development of innovative stem cell and gene editing therapeutic approaches. Even though tumorigenicity and immunogenicity are existing hurdles, we report how recent progress has tackled them, making engineered stem cell transplantation therapy a realistic option.

CRISPR/Cas9 Genome Editing Tool: A Promising Tool for Therapeutic Applications on Respiratory Diseases

2020 ◽  
Vol 20 (5) ◽  
pp. 333-346
Author(s):  
Sadiya Bi Shaikh ◽  
Yashodhar Prabhakar Bhandary
Keyword(s):  
Respiratory Diseases ◽  
Gene Editing ◽  
Epithelial Mesenchymal Transition ◽  
Respiratory Health ◽  
Chronic Obstructive ◽  
Therapeutic Tool ◽  
Obstructive Pulmonary Disease ◽  
Mesenchymal Transition ◽  
Chronic Respiratory Diseases ◽  
Promising Tool

Respiratory diseases are one of the prime topics of concern in the current era due to improper diagnostics tools. Gene-editing therapy, like Clustered regularly interspaced palindromic repeats- associated nuclease 9 (CRISPR/Cas9), is gaining popularity in pulmonary research, opening up doors to invaluable insights on underlying mechanisms. CRISPR/Cas9 can be considered as a potential gene-editing tool with a scientific community that is helping in the advancement of knowledge in respiratory health and therapy. As an appealing therapeutic tool, we hereby explore the advanced research on the application of CRISPR/Cas9 tools in chronic respiratory diseases such as lung cancer, Acute respiratory distress syndrome (ARDS) and cystic fibrosis (CF). We also address the urgent need to establish this gene-editing tool in various other lung diseases such as asthma, Chronic obstructive pulmonary disease (COPD) and Idiopathic pulmonary fibrosis (IPF). The present review introduces CRISPR/Cas9 as a worthy application in targeting epithelial-mesenchymal transition and fibrinolytic system via editing specific genes. Thereby, based on the efficiency of CRISPR/Cas9, it can be considered as a promising therapeutic tool in respiratory health research.

scholarly journals Epigenetic reprogramming of cell identity: lessons from development for regenerative medicine

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Amitava Basu ◽  
Vijay K. Tiwari
Keyword(s):  
Regenerative Medicine ◽  
Cell Types ◽  
Direct Conversion ◽  
Cellular Reprogramming ◽  
Specific Cell ◽  
Cell Type ◽  
Pathological Conditions ◽  
Gene Regulatory ◽  
Induced Pluripotent ◽  
And Function

AbstractEpigenetic mechanisms are known to define cell-type identity and function. Hence, reprogramming of one cell type into another essentially requires a rewiring of the underlying epigenome. Cellular reprogramming can convert somatic cells to induced pluripotent stem cells (iPSCs) that can be directed to differentiate to specific cell types. Trans-differentiation or direct reprogramming, on the other hand, involves the direct conversion of one cell type into another. In this review, we highlight how gene regulatory mechanisms identified to be critical for developmental processes were successfully used for cellular reprogramming of various cell types. We also discuss how the therapeutic use of the reprogrammed cells is beginning to revolutionize the field of regenerative medicine particularly in the repair and regeneration of damaged tissue and organs arising from pathological conditions or accidents. Lastly, we highlight some key challenges hindering the application of cellular reprogramming for therapeutic purposes.

scholarly journals Non-viral delivery of CRISPR–Cas9 complexes for targeted gene editing via a polymer delivery system

Gene Therapy ◽  
2021 ◽  
Author(s):  
Jonathan O’Keeffe Ahern ◽  
Irene Lara-Sáez ◽  
Dezhong Zhou ◽  
Rodolfo Murillas ◽  
Jose Bonafont ◽  
...  
Keyword(s):  
Delivery System ◽  
Gene Editing ◽  
Transfection Efficiency ◽  
Attractive Alternative ◽  
Safe Delivery ◽  
Guide Rna ◽  
Recessive Dystrophic Epidermolysis Bullosa ◽  
Targeted Gene Editing ◽  
Genomic Editing ◽  
Polymeric Vectors

AbstractRecent advances in molecular biology have led to the CRISPR revolution, but the lack of an efficient and safe delivery system into cells and tissues continues to hinder clinical translation of CRISPR approaches. Polymeric vectors offer an attractive alternative to viruses as delivery vectors due to their large packaging capacity and safety profile. In this paper, we have demonstrated the potential use of a highly branched poly(β-amino ester) polymer, HPAE-EB, to enable genomic editing via CRISPRCas9-targeted genomic excision of exon 80 in the COL7A1 gene, through a dual-guide RNA sequence system. The biophysical properties of HPAE-EB were screened in a human embryonic 293 cell line (HEK293), to elucidate optimal conditions for efficient and cytocompatible delivery of a DNA construct encoding Cas9 along with two RNA guides, obtaining 15–20% target genomic excision. When translated to human recessive dystrophic epidermolysis bullosa (RDEB) keratinocytes, transfection efficiency and targeted genomic excision dropped. However, upon delivery of CRISPR–Cas9 as a ribonucleoprotein complex, targeted genomic deletion of exon 80 was increased to over 40%. Our study provides renewed perspective for the further development of polymer delivery systems for application in the gene editing field in general, and specifically for the treatment of RDEB.

scholarly journals iPS-Cell Technology and the Problem of Genetic Instability—Can It Ever Be Safe for Clinical Use?

2019 ◽  
Vol 8 (3) ◽  
pp. 288 ◽  
Author(s):  
Stephen Attwood ◽  
Michael Edel
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Great Promise ◽  
Clinical Use ◽  
Medicinal Products ◽  
Ips Cell ◽  
Factors Affecting ◽  
Induced Pluripotent ◽  
Stem Cell Therapeutics

The use of induced Pluripotent Stem Cells (iPSC) as a source of autologous tissues shows great promise in regenerative medicine. Nevertheless, several major challenges remain to be addressed before iPSC-derived cells can be used in therapy, and experience of their clinical use is extremely limited. In this review, the factors affecting the safe translation of iPSC to the clinic are considered, together with an account of efforts being made to overcome these issues. The review draws upon experiences with pluripotent stem-cell therapeutics, including clinical trials involving human embryonic stem cells and the widely transplanted mesenchymal stem cells. The discussion covers concerns relating to: (i) the reprogramming process; (ii) the detection and removal of incompletely differentiated and pluripotent cells from the resulting medicinal products; and (iii) genomic and epigenetic changes, and the evolutionary and selective processes occurring during culture expansion, associated with production of iPSC-therapeutics. In addition, (iv) methods for the practical culture-at-scale and standardization required for routine clinical use are considered. Finally, (v) the potential of iPSC in the treatment of human disease is evaluated in the light of what is known about the reprogramming process, the behavior of cells in culture, and the performance of iPSC in pre-clinical studies.

Sign in / Sign up

Export Citation Format

Share Document