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Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 96048

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Prof. Dr. Luisa Barzon

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Department of Molecular Medicine, University of Padova, 35121 Padova, Italy
Interests: surveillance, diagnosis, and pathogenesis of emerging vector-borne viral infections; pathogenesis, diagnosis, and prevention of human papillomavirus-related diseases; investigation of virus–host interactions; development of patient-specific models of human susceptibility to viral infections; application of innovative molecular methods in infectious disease diagnosis
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Prof. Marta Trevisan

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Department of Molecular Medicine, University of Padova, 35121 Padova, Italy
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Dear Colleagues,

Recent advances in cell reprogramming and genome editing technologies that allow the generation of patient-specific induced pluripotent stem cells (iPSCs) from differentiated somatic cells and their genetic modification has provided unprecedented sources of human cells for regenerative medicine applications and models to study human diseases. Human iPSCs have been generated from a variety of somatic cells and have been differentiated into almost any cell type of the body, including disease-relevant cell types, like cardiomyocytes, hepatocytes, and neurons. These cells have been also successfully used to recreate mini-organs in a petri dish that recapitulate the cytoarchitecture of the diseased tissue from a pathophysiological and a molecular point of view. If derived from patients with a disease phenotype, these cells will express the entire genetic background of the patient and the genetic modifiers that have a role in disease pathogenesis. Moreover, patient-specific iPSC-derived cells enable personalized therapies and can be employed to either discover new therapeutics or perform toxicity assays in high-throughput screenings. Applications include monogenic diseases, but even complex and multi-factorial disorders, such as cancer, degenerative, psychiatric, and infectious diseases.

We invite you to contribute original articles that describe iPSC-derived disease-in-a-dish models, their use in the recapitulation and the deepening of the molecular mechanisms underlying the disease, and in drug discovery studies. Review articles are also welcome.

Prof. Luisa Barzon
Prof. Marta Trevisan
Guest Editors

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Keywords

Induced pluripotent stem cells
Organoids
Organ-on-chip technologies
Patient-specific disease model
Genome editing
Disease modeling
Regenerative medicine
Drug discovery
Drug testing and toxicity
Clinical trials in the dish
Personalized medicine

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Published Papers (13 papers)

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Research

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16 pages, 4758 KiB

Open AccessArticle

Modeling of Frontotemporal Dementia Using iPSC Technology

by Minchul Kim, Hee Jin Kim, Wonyoung Koh, Ling Li, Hyohoon Heo, Hanna Cho, Chul Hyoung Lyoo, Sang Won Seo, Eun-Joo Kim, Mahito Nakanishi, Duk L. Na and Jihwan Song

Int. J. Mol. Sci. 2020, 21(15), 5319; https://doi.org/10.3390/ijms21155319 - 27 Jul 2020

Cited by 10 | Viewed by 4292

Abstract

Frontotemporal dementia (FTD) is caused by the progressive degeneration of the frontal and temporal lobes of the brain. Behavioral variant FTD (bvFTD) is the most common clinical subtype of FTD and pathological subtypes of bvFTD are known as FTD-tau, transactive response (TAR) DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS). Pathological mechanisms of bvFTD are largely unknown. In this study, we investigated the expression of pathological markers, such as p-Tau, TDP-43, and FUS, in the induced pluripotent stem-cell-derived neurons (iPSN) from two sporadic bvFTD patients and one normal subject. We also used an FTD-patient-derived iPSC-line-carrying microtubule-associated protein tau (MAPT) P301L point mutation as positive control for p-Tau expression. Staurosporine (STS) was used to induce cellular stress in order to investigate dynamic cellular responses related to the cell death pathway. As a result, the expression of active caspase-3 was highly increased in the bvFTD-iPSNs compared with control iPSNs in the STS-treated conditions. Other cell-death-related proteins, including Bcl-2-associated X protein (Bax)/Bcl-2 and cytochrome C, were also increased in the bvFTD-iPSNs. Moreover, we observed abnormal expression patterns of TDP-43 and FUS in the bvFTD-iPSNs compared with control iPSNs. We suggest that the iPSC technology might serve as a potential tool to demonstrate neurodegenerative phenotypes of bvFTD, which will be useful for studying pathological mechanisms for FTD as well as related drug screening in the future. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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15 pages, 4640 KiB

Open AccessArticle

Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells

by Elena Naumovska, Germaine Aalderink, Christian Wong Valencia, Kinga Kosim, Arnaud Nicolas, Stephen Brown, Paul Vulto, Kai S. Erdmann and Dorota Kurek

Int. J. Mol. Sci. 2020, 21(14), 4964; https://doi.org/10.3390/ijms21144964 - 14 Jul 2020

Cited by 57 | Viewed by 9739

Abstract

Intestinal organoids have emerged as the new paradigm for modelling the healthy and diseased intestine with patient-relevant properties. In this study, we show directed differentiation of induced pluripotent stem cells towards intestinal-like phenotype within a microfluidic device. iPSCs are cultured against a gel in microfluidic chips of the OrganoPlate, in which they undergo stepwise differentiation. Cells form a tubular structure, lose their stem cell markers and start expressing mature intestinal markers, including markers for Paneth cells, enterocytes and neuroendocrine cells. Tubes develop barrier properties as confirmed by transepithelial electrical resistance (TEER). Lastly, we show that tubules respond to pro-inflammatory cytokine triggers. The whole procedure for differentiation lasts 14 days, making it an efficient process to make patient-specific organoid tubules. We anticipate the usage of the platform for disease modelling and drug candidate screening. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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23 pages, 6383 KiB

Open AccessArticle

Large-Scale Production of Human iPSC-Derived Macrophages for Drug Screening

by Simon Gutbier, Florian Wanke, Nadine Dahm, Anna Rümmelin, Silke Zimmermann, Klaus Christensen, Fabian Köchl, Anna Rautanen, Klas Hatje, Barbara Geering, Jitao David Zhang, Markus Britschgi, Sally A. Cowley and Christoph Patsch

Int. J. Mol. Sci. 2020, 21(13), 4808; https://doi.org/10.3390/ijms21134808 - 7 Jul 2020

Cited by 67 | Viewed by 13983

Abstract

Tissue-resident macrophages are key players in inflammatory processes, and their activation and functionality are crucial in health and disease. Numerous diseases are associated with alterations in homeostasis or dysregulation of the innate immune system, including allergic reactions, autoimmune diseases, and cancer. Macrophages are a prime target for drug discovery due to their major regulatory role in health and disease. Currently, the main sources of macrophages used for therapeutic compound screening are primary cells isolated from blood or tissue or immortalized or neoplastic cell lines (e.g., THP-1). Here, we describe an improved method to employ induced pluripotent stem cells (iPSCs) for the high-yield, large-scale production of cells resembling tissue-resident macrophages. For this, iPSC-derived macrophage-like cells are thoroughly characterized to confirm their cell identity and thus their suitability for drug screening purposes. These iPSC-derived macrophages show strong cellular identity with primary macrophages and recapitulate key functional characteristics, including cytokine release, phagocytosis, and chemotaxis. Furthermore, we demonstrate that genetic modifications can be readily introduced at the macrophage-like progenitor stage in order to interrogate drug target-relevant pathways. In summary, this novel method overcomes previous shortcomings with primary and leukemic cells and facilitates large-scale production of genetically modified iPSC-derived macrophages for drug screening applications. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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16 pages, 3630 KiB

Open AccessArticle

Iroquois Homeobox Protein 2 Identified as a Potential Biomarker for Parkinson’s Disease

by Hyuna Sim, Joo-Eun Lee, Hee Min Yoo, Sunwha Cho, Hana Lee, Aruem Baek, Jisun Kim, Hyemyung Seo, Mi-Na Kweon, Hyung Gun Kim, Young-Joo Jeon, Mi-Young Son and Janghwan Kim

Int. J. Mol. Sci. 2020, 21(10), 3455; https://doi.org/10.3390/ijms21103455 - 14 May 2020

Cited by 6 | Viewed by 3925

Abstract

The diagnosis of Parkinson’s disease (PD) is initiated after the occurrence of motor symptoms, such as resting tremors, rigidity, and bradykinesia. According to previous reports, non-motor symptoms, notably gastrointestinal dysfunction, could potentially be early biomarkers in PD patients as such symptoms occur earlier than motor symptoms. However, connecting PD to the intestine is methodologically challenging. Thus, we generated in vitro human intestinal organoids from PD patients and ex vivo mouse small intestinal organoids from aged transgenic mice. Both intestinal organoids (IOs) contained the human LRRK2 G2019S mutation, which is the most frequent genetic cause of familial and sporadic PD. By conducting comprehensive genomic comparisons with these two types of IOs, we determined that a particular gene, namely, Iroquois homeobox protein 2 (IRX2), showed PD-related expression patterns not only in human pluripotent stem cell (PSC)-derived neuroectodermal spheres but also in human PSC-derived neuronal cells containing dopaminergic neurons. We expected that our approach of using various cell types presented a novel technical method for studying the effects of multi-organs in PD pathophysiology as well as for the development of diagnostic markers for PD. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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16 pages, 2327 KiB

Open AccessArticle

Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells

by Karin Jennbacken, Fredrik Wågberg, Ulla Karlsson, Jerry Eriksson, Lisa Magnusson, Marjorie Chimienti, Piero Ricchiuto, Jenny Bernström, Mei Ding, Douglas Ross-Thriepland, Yafeng Xue, Diluka Peiris, Teodor Aastrup, Hanna Tegel, Sophia Hober, Åsa Sivertsson, Mathias Uhlén, Per-Erik Strömstedt, Rick Davies and Lovisa Holmberg Schiavone

Int. J. Mol. Sci. 2019, 20(23), 6037; https://doi.org/10.3390/ijms20236037 - 30 Nov 2019

Cited by 16 | Viewed by 6199

Abstract

Paracrine factors can induce cardiac regeneration and repair post myocardial infarction by stimulating proliferation of cardiac cells and inducing the anti-fibrotic, antiapoptotic, and immunomodulatory effects of angiogenesis. Here, we screened a human secretome library, consisting of 923 growth factors, cytokines, and proteins with unknown function, in a phenotypic screen with human cardiac progenitor cells. The primary readout in the screen was proliferation measured by nuclear count. From this screen, we identified FGF1, FGF4, FGF9, FGF16, FGF18, and seven additional proteins that induce proliferation of cardiac progenitor cells. FGF9 and FGF16 belong to the same FGF subfamily, share high sequence identity, and are described to have similar receptor preferences. Interestingly, FGF16 was shown to be specific for proliferation of cardiac progenitor cells, whereas FGF9 also proliferated human cardiac fibroblasts. Biosensor analysis of receptor preferences and quantification of receptor abundances suggested that FGF16 and FGF9 bind to different FGF receptors on the cardiac progenitor cells and cardiac fibroblasts. FGF16 also proliferated naïve cardiac progenitor cells isolated from mouse heart and human cardiomyocytes derived from induced pluripotent cells. Taken together, the data suggest that FGF16 could be a suitable paracrine factor to induce cardiac regeneration and repair. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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18 pages, 7245 KiB

Open AccessArticle

Modelling Neurotropic Flavivirus Infection in Human Induced Pluripotent Stem Cell-Derived Systems

by Giovanna Desole, Alessandro Sinigaglia, Silvia Riccetti, Giulia Masi, Monia Pacenti, Marta Trevisan and Luisa Barzon

Int. J. Mol. Sci. 2019, 20(21), 5404; https://doi.org/10.3390/ijms20215404 - 30 Oct 2019

Cited by 23 | Viewed by 4341

Abstract

Generation of human induced pluripotent stem cells (hiPSCs) and their differentiation into a variety of cells and organoids have allowed setting up versatile, non-invasive, ethically sustainable, and patient-specific models for the investigation of the mechanisms of human diseases, including viral infections and host–pathogen interactions. In this study, we investigated and compared the infectivity and replication kinetics in hiPSCs, hiPSC-derived neural stem cells (NSCs) and undifferentiated neurons, and the effect of viral infection on host innate antiviral responses of representative flaviviruses associated with diverse neurological diseases, i.e., Zika virus (ZIKV), West Nile virus (WNV), and dengue virus (DENV). In addition, we exploited hiPSCs to model ZIKV infection in the embryo and during neurogenesis. The results of this study confirmed the tropism of ZIKV for NSCs, but showed that WNV replicated in these cells with much higher efficiency than ZIKV and DENV, inducing massive cell death. Although with lower efficiency, all flaviviruses could also infect pluripotent stem cells and neurons, inducing similar patterns of antiviral innate immune response gene expression. While showing the usefulness of hiPSC-based infection models, these findings suggest that additional virus-specific mechanisms, beyond neural tropism, are responsible for the peculiarities of disease phenotype in humans. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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Review

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28 pages, 863 KiB

Open AccessReview

Versatility of Induced Pluripotent Stem Cells (iPSCs) for Improving the Knowledge on Musculoskeletal Diseases

by Clara Sanjurjo-Rodríguez, Rocío Castro-Viñuelas, María Piñeiro-Ramil, Silvia Rodríguez-Fernández, Isaac Fuentes-Boquete, Francisco J. Blanco and Silvia Díaz-Prado

Int. J. Mol. Sci. 2020, 21(17), 6124; https://doi.org/10.3390/ijms21176124 - 25 Aug 2020

Cited by 9 | Viewed by 4038

Abstract

Induced pluripotent stem cells (iPSCs) represent an unlimited source of pluripotent cells capable of differentiating into any cell type of the body. Several studies have demonstrated the valuable use of iPSCs as a tool for studying the molecular and cellular mechanisms underlying disorders affecting bone, cartilage and muscle, as well as their potential for tissue repair. Musculoskeletal diseases are one of the major causes of disability worldwide and impose an important socio-economic burden. To date there is neither cure nor proven approach for effectively treating most of these conditions and therefore new strategies involving the use of cells have been increasingly investigated in the recent years. Nevertheless, some limitations related to the safety and differentiation protocols among others remain, which humpers the translational application of these strategies. Nonetheless, the potential is indisputable and iPSCs are likely to be a source of different types of cells useful in the musculoskeletal field, for either disease modeling or regenerative medicine. In this review, we aim to illustrate the great potential of iPSCs by summarizing and discussing the in vitro tissue regeneration preclinical studies that have been carried out in the musculoskeletal field by using iPSCs. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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30 pages, 2306 KiB

Open AccessReview

Modeling Cardiac Disease Mechanisms Using Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Progress, Promises and Challenges

by Elvira Immacolata Parrotta, Valeria Lucchino, Luana Scaramuzzino, Stefania Scalise and Giovanni Cuda

Int. J. Mol. Sci. 2020, 21(12), 4354; https://doi.org/10.3390/ijms21124354 - 19 Jun 2020

Cited by 60 | Viewed by 7887

Abstract

Cardiovascular diseases (CVDs) are a class of disorders affecting the heart or blood vessels. Despite progress in clinical research and therapy, CVDs still represent the leading cause of mortality and morbidity worldwide. The hallmarks of cardiac diseases include heart dysfunction and cardiomyocyte death, inflammation, fibrosis, scar tissue, hyperplasia, hypertrophy, and abnormal ventricular remodeling. The loss of cardiomyocytes is an irreversible process that leads to fibrosis and scar formation, which, in turn, induce heart failure with progressive and dramatic consequences. Both genetic and environmental factors pathologically contribute to the development of CVDs, but the precise causes that trigger cardiac diseases and their progression are still largely unknown. The lack of reliable human model systems for such diseases has hampered the unraveling of the underlying molecular mechanisms and cellular processes involved in heart diseases at their initial stage and during their progression. Over the past decade, significant scientific advances in the field of stem cell biology have literally revolutionized the study of human disease in vitro. Remarkably, the possibility to generate disease-relevant cell types from induced pluripotent stem cells (iPSCs) has developed into an unprecedented and powerful opportunity to achieve the long-standing ambition to investigate human diseases at a cellular level, uncovering their molecular mechanisms, and finally to translate bench discoveries into potential new therapeutic strategies. This review provides an update on previous and current research in the field of iPSC-driven cardiovascular disease modeling, with the aim of underlining the potential of stem-cell biology-based approaches in the elucidation of the pathophysiology of these life-threatening diseases. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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15 pages, 752 KiB

Open AccessReview

CRISPR/Cas9-Mediated Gene Correction to Understand ALS

by Yeomin Yun and Yoon Ha

Int. J. Mol. Sci. 2020, 21(11), 3801; https://doi.org/10.3390/ijms21113801 - 27 May 2020

Cited by 32 | Viewed by 10161

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the death of motor neurons in the spinal cord and brainstem. ALS has a diverse genetic origin; at least 20 genes have been shown to be related to ALS. Most familial and sporadic cases of ALS are caused by variants of the SOD1, C9orf72, FUS, and TARDBP genes. Genome editing using clustered regularly interspaced short palindromic repeats/CRISPR-associated system 9 (CRISPR/Cas9) can provide insights into the underlying genetics and pathophysiology of ALS. By correcting common mutations associated with ALS in animal models and patient-derived induced pluripotent stem cells (iPSCs), CRISPR/Cas9 has been used to verify the effects of ALS-associated mutations and observe phenotype differences between patient-derived and gene-corrected iPSCs. This technology has also been used to create mutations to investigate the pathophysiology of ALS. Here, we review recent studies that have used CRISPR/Cas9 to understand the genetic underpinnings of ALS. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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32 pages, 1088 KiB

Open AccessReview

Modeling Cardiovascular Diseases with hiPSC-Derived Cardiomyocytes in 2D and 3D Cultures

by Claudia Sacchetto, Libero Vitiello, Leon J. de Windt, Alessandra Rampazzo and Martina Calore

Int. J. Mol. Sci. 2020, 21(9), 3404; https://doi.org/10.3390/ijms21093404 - 11 May 2020

Cited by 58 | Viewed by 8638

Abstract

In the last decade, the generation of cardiac disease models based on human-induced pluripotent stem cells (hiPSCs) has become of common use, providing new opportunities to overcome the lack of appropriate cardiac models. Although much progress has been made toward the generation of hiPSC-derived cardiomyocytes (hiPS-CMs), several lines of evidence indicate that two-dimensional (2D) cell culturing presents significant limitations, including hiPS-CMs immaturity and the absence of interaction between different cell types and the extracellular matrix. More recently, new advances in bioengineering and co-culture systems have allowed the generation of three-dimensional (3D) constructs based on hiPSC-derived cells. Within these systems, biochemical and physical stimuli influence the maturation of hiPS-CMs, which can show structural and functional properties more similar to those present in adult cardiomyocytes. In this review, we describe the latest advances in 2D- and 3D-hiPSC technology for cardiac disease mechanisms investigation, drug development, and therapeutic studies. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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15 pages, 1423 KiB

Open AccessReview

Recent Overview of the Use of iPSCs Huntington’s Disease Modeling and Therapy

by Maria Csobonyeiova, Stefan Polak and Lubos Danisovic

Int. J. Mol. Sci. 2020, 21(6), 2239; https://doi.org/10.3390/ijms21062239 - 24 Mar 2020

Cited by 38 | Viewed by 7566

Abstract

Huntington’s disease (HD) is an inherited, autosomal dominant, degenerative disease characterized by involuntary movements, cognitive decline, and behavioral impairment ending in death. HD is caused by an expansion in the number of CAG repeats in the huntingtin gene on chromosome 4. To date, no effective therapy for preventing the onset or progression of the disease has been found, and many symptoms do not respond to pharmacologic treatment. However, recent results of pre-clinical trials suggest a beneficial effect of stem-cell-based therapy. Induced pluripotent stem cells (iPSCs) represent an unlimited cell source and are the most suitable among the various types of autologous stem cells due to their patient specificity and ability to differentiate into a variety of cell types both in vitro and in vivo. Furthermore, the cultivation of iPSC-derived neural cells offers the possibility of studying the etiopathology of neurodegenerative diseases, such as HD. Moreover, differentiated neural cells can organize into three-dimensional (3D) organoids, mimicking the complex architecture of the brain. In this article, we present a comprehensive review of recent HD models, the methods for differentiating HD–iPSCs into the desired neural cell types, and the progress in gene editing techniques leading toward stem-cell-based therapy. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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18 pages, 1827 KiB

Open AccessReview

Progress in iPSC-Based Modeling of Psychiatric Disorders

by Anke Hoffmann, Michael Ziller and Dietmar Spengler

Int. J. Mol. Sci. 2019, 20(19), 4896; https://doi.org/10.3390/ijms20194896 - 2 Oct 2019

Cited by 28 | Viewed by 6288

Abstract

Progress in iPSC-based cellular systems provides new insights into human brain development and early neurodevelopmental deviations in psychiatric disorders. Among these, studies on schizophrenia (SCZ) take a prominent role owing to its high heritability and multifarious evidence that it evolves from a genetically induced vulnerability in brain development. Recent iPSC studies on patients with SCZ indicate that functional impairments of neural progenitor cells (NPCs) in monolayer culture extend to brain organoids by disrupting neocorticogenesis in an in vitro model. In addition, the formation of hippocampal circuit-like structures in vitro is impaired in patients with SCZ as is the case for glia development. Intriguingly, chimeric-mice experiments show altered oligodendrocyte and astrocyte development in vivo that highlights the importance of cell–cell interactions in the pathogenesis of early-onset SCZ. Likewise, cortical imbalances in excitatory–inhibitory signaling may result from a cell-autonomous defect in cortical interneuron (cIN) development. Overall, these findings indicate that genetic risk in SCZ impacts neocorticogenesis, hippocampal circuit formation, and the development of distinct glial and neuronal subtypes. In light of this remarkable progress, we discuss current limitations and further steps necessary to harvest the full potential of iPSC-based investigations on psychiatric disorders. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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13 pages, 972 KiB

Open AccessReview

Recent Progress in the Regeneration of Spinal Cord Injuries by Induced Pluripotent Stem Cells

by Maria Csobonyeiova, Stefan Polak, Radoslav Zamborsky and Lubos Danisovic

Int. J. Mol. Sci. 2019, 20(15), 3838; https://doi.org/10.3390/ijms20153838 - 6 Aug 2019

Cited by 36 | Viewed by 8127

Abstract

Regeneration of injuries occurring in the central nervous system, particularly spinal cord injuries (SCIs), is extremely difficult. The complex pathological events following a SCI often restrict regeneration of nervous tissue at the injury site and frequently lead to irreversible loss of motor and sensory function. Neural stem/progenitor cells (NSCs/NPCs) possess neuroregenerative and neuroprotective features, and transplantation of such cells into the site of damaged tissue is a promising stem cell-based therapy for SCI. However, NSC/NPCs have mostly been induced from embryonic stem cells or fetal tissue, leading to ethical concerns. The pioneering work of Yamanaka and colleagues gave rise to the technology to induce pluripotent stem cells (iPSCs) from somatic cells, overcoming these ethical issues. The advent of iPSCs technology has meant significant progress in the therapy of neurodegenerative disease and nerve tissue damage. A number of published studies have described the successful differentiation of NSCs/NPCs from iPSCs and their subsequent engraftment into SCI animal models, followed by functional recovery of injury. The aim of this present review is to summarize various iPSC- NPCs differentiation methods, SCI modelling, and the current status of possible iPSC- NPCs- based therapy of SCI. Full article

(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)

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