scholarly journals Gene Editing Correction of a Urea Cycle Defect in Organoid Stem Cell Derived Hepatocyte-like Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1217
Author(s):  
Mihaela Zabulica ◽  
Tomas Jakobsson ◽  
Francesco Ravaioli ◽  
Massoud Vosough ◽  
Roberto Gramignoli ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Diseases ◽  
Urea Cycle ◽  
Definitive Treatment ◽  
Phenotypic Change ◽  
Cell Based Therapy ◽  
Hepatic Diseases ◽  
Number Of Patients ◽  
Urea Cycle Defect

Urea cycle disorders are enzymopathies resulting from inherited deficiencies in any genes of the cycle. In severe cases, currently available therapies are marginally effective, with liver transplantation being the only definitive treatment. Donor liver availability can limit even this therapy. Identification of novel therapeutics for genetic-based liver diseases requires models that provide measurable hepatic functions and phenotypes. Advances in stem cell and genome editing technologies could provide models for the investigation of cell-based genetic diseases, as well as the platforms for drug discovery. This report demonstrates a practical, and widely applicable, approach that includes the successful reprogramming of somatic cells from a patient with a urea cycle defect, their genetic correction and differentiation into hepatic organoids, and the subsequent demonstration of genetic and phenotypic change in the edited cells consistent with the correction of the defect. While individually rare, there is a large number of other genetic-based liver diseases. The approach described here could be applied to a broad range and a large number of patients with these hepatic diseases where it could serve as an in vitro model, as well as identify successful strategies for corrective cell-based therapy.

In vitro recapitulation of the urea cycle using murine embryonic stem cell-derived in vitro liver model

Amino Acids ◽  
2013 ◽  
Vol 45 (6) ◽  
pp. 1343-1351 ◽  
Author(s):  
Miho Tamai ◽  
Mami Aoki ◽  
Akihito Nishimura ◽  
Koji Morishita ◽  
Yoh-ichi Tagawa
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Urea Cycle ◽  
Embryonic Stem ◽  
Murine Embryonic Stem Cell ◽  
Liver Model

Amniotic Stem Cell-Conditioned Media for the Treatment of Nerve and Muscle Pathology: A Systematic Review

2021 ◽  
Author(s):  
Chukwuweike Gwam ◽  
Ahmed Emara ◽  
Nequesha Mohamed ◽  
Noor Chughtai ◽  
Johannes Plate ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tissue Regeneration ◽  
Cell Damage ◽  
Conditioned Media ◽  
Nerve Tissue ◽  
Muscle Pathology ◽  
Loss Of Function ◽  
Cell Based Therapy

Muscle and nerve tissue damage can elicit a significant loss of function and poses as a burden for patients and healthcare providers. Even for tissues, such as the peripheral nerve and skeletal muscle, that harbor significant regenerative capacity, innate regenerative processes often lead to less than optimal recovery and residual loss of function. The reasons for poor regeneration include significant cell damage secondary to oxidative stress, poor recruitment of resident stem cells, and an unfavorable microenvironment for tissue regeneration. Stem cell-based therapy was once thought as a potential therapy in tissue regeneration, due to its self-renewal and multipotent capabilities. Early advocates for cellular-based therapy pointed to the pluripotent nature of stem cells, thus eluding to its ability to differentiate into resident cells as the source of its regenerative capability. However, increasing evidence has revealed a lack of engraftment and differentiation of stem cells, thereby pointing to stem cell paracrine activity as being responsible for its regenerative potential. Stem cell-conditioned media houses biomolecular factors that portray significant regenerative potential. Amniotic-derived stem cell-conditioned media (AFS-CM) has been of particular interest because of its ease of allocation and in vitro culture. The purpose of this review is to report the results of studies that assess the role of AFS-CM for nerve and muscle conditions. In this review, we will cover the effects of AFS-CM on cellular pathways, genes, and protein expression for different nerve and muscle cell types.

Stem cells in brain diseases: From cell replacement to disease modeling

2011 ◽  
Vol 2 (2) ◽  
Author(s):  
Nina Kosi ◽  
Dinko Mitrečić
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Disease Modeling ◽  
Neurological Diseases ◽  
Rapid Development ◽  
Modern Society ◽  
Brain Diseases ◽  
Stem Cell Technology ◽  
Cell Based Therapy

AbstractNeurological diseases are recognized as one of the most significant burdens of the modern society. Therefore, a new therapeutic approach applicable to nervous system represents priority of today’s medicine. A rapid development of stem cell technology in the last two decades introduced a possibility to regenerate disease-affected nervous tissue. In this vein, stem cells are envisioned as a replacement for lost neurons, a source of trophic support, a therapeutic vehicle, and as a tool for in vitro modeling. This article reviews the current concepts in stem cell-based therapy of neurological diseases and comments ongoing efforts aiming at clinical translation.

Systematic Intracellular Biocompatibility Assessments of Superparamagnetic Iron Oxide Nanoparticles in Human Umbilical Cord Mesenchyme Stem Cells in Testifying Its Reusability for Inner Cell Tracking by MRI

2019 ◽  
Vol 15 (11) ◽  
pp. 2179-2192
Author(s):  
Yuanyuan Xie ◽  
Wei Liu ◽  
Bing Zhang ◽  
Bin Wang ◽  
Liudi Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Umbilical Cord ◽  
Cell Tracking ◽  
Superparamagnetic Iron Oxide ◽  
Human Umbilical Cord ◽  
Cell Based Therapy

Until now, there is no effective method for tracking transplanted stem cells in human. Ruicun (RC) is a new ultra-small SPIONs agent that has been approved by China Food and Drug Administration for iron supplementation but not as a stem cell tracer in clinic. In this study, we demonstrated magnetic resonance imaging-based tracking of RC-labeled human umbilical cord derived mesenchymal stem cells (MSCs) transplanted to locally injured site of rat spinal cords. We then comprehensively evaluated the safety and quality of the RC-labeled MSCs under good manufacturing practicecompliant conditions, to investigate the feasibility of SPIONs for inner tracking in stem cell-based therapy (SCT). Our results showed that RC labeling at appropriate dose (200 μg/mL) did not have evident impacts on characteristics of MSCs in vitro, demonstrating safety, non-carcinogenesis, and non-tissue inflammation in vivo. The systematic assessments of intracellular biocompatibility indicated that the RC labeled MSCs met with mandatory requirements and standards for law-regulation systems regarding SCT, facilitating translation of cell-tracking technologies to clinical trials.

scholarly journals Effect of Astragaloside IV on Neural Stem Cell Transplantation in Alzheimer’s Disease Rat Models

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Hu Haiyan ◽  
Yang Rensong ◽  
Jin Guoqin ◽  
Zhang Xueli ◽  
Xia Huaying ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Stem Cell ◽  
Learning And Memory ◽  
High Dose ◽  
Astragaloside Iv ◽  
Cell Based Therapy ◽  
Proliferation And Differentiation

Stem cell-based therapy is a promising treatment strategy for neurodegenerative diseases such as Alzheimer’s disease (AD). However, the mechanism underlying the maintenance of renewal and replacement capabilities of endogenous progenitor cells or engrafted stem cells in a pathological environment remains elusive. To investigate the effect of astragaloside IV (ASI) on the proliferation and differentiation of the engrafted neural stem cells (NSCs), we cultured NSCs from the hippocampus of E14 rat embryos, treated the cells with ASI, and then transplanted the cells into the hippocampus of rat AD models.In vitroexperimentation showed that 10−5 M ASI induced NSCs to differentiate intoβ-tubulin III+and GFAP+cells. NSCs transplantation into rat AD models resulted in improvements in learning and memory, especially in the ASI-treated groups. ASI treatment resulted in an increase in the number ofβ-tubulin III+cells in the hippocampus. Further investigation showed that ASI inhibited PS1 expressionin vitroandin vivo. The high-dose ASI downregulated the Notch intracellular domain, whereas the low-dose ASI increased Notch-1 and NICD. In conclusion, ASI treatment resulted in improvements in learning and memory of AD models by promoting NSC proliferation and differentiation partly through the Notch signal pathway.

scholarly journals Reprogrammed Cell?based Therapy for Liver Disease: From Lab to Clinic

2017 ◽  
Vol 1 (1) ◽  
pp. 20-28 ◽  
Author(s):  
Amir Mehdizadeh ◽  
Masoud Darabi
Keyword(s):  
Cellular Reprogramming ◽  
Gene Correction ◽  
In Vitro Production ◽  
Efficient Treatment ◽  
Cell Based Therapy ◽  
Number Of Patients ◽  
End Stage ◽  
Vitro Production

A large number of patients are affected by liver dysfunction worldwide. Liver transplantation is the only efficient treatment in a variety of enduring liver disorders including inherent and end-stage liver diseases. The generation of human functional hepatocytes in high quantities for liver cell therapy is an important goal for ongoing therapies in regenerative medicine. Reprogrammed cells are considered as a promising and unlimited source of hepatocytes, mainly because of their expected lack of immunogenicity and minimized ethical concerns in clinical applications. Despite gained advances in the reprogramming of somatic cells to functional hepatocytes in vitro, production of primary adult hepatocytes that can proliferate in vivo still remains inaccessible. As part of efforts toward translation of cell reprogramming science into clinical practice, more careful cell selection strategies should be integrated into improvement of dedifferentiation and redifferentiation protocols, especially in precision medicine where gene correction is needed. Furthermore, advances in cellular reprogramming highlight the need for developing and evaluating novel standards addressing clinical research interests in this field.

scholarly journals Xenogeneic and Stem Cell-Based Therapy for Cardiovascular Diseases: Genetic Engineering of Porcine Cells and Their Applications in Heart Regeneration

2020 ◽  
Vol 21 (24) ◽  
pp. 9686
Author(s):  
Anne-Marie Galow ◽  
Tom Goldammer ◽  
Andreas Hoeflich
Keyword(s):  
Stem Cell ◽  
Cardiovascular Diseases ◽  
Health Concern ◽  
Heart Regeneration ◽  
Major Health ◽  
Cell Replacement ◽  
Cell Based Therapy ◽  
Intensive Investigation ◽  
Technological Limitations

Cardiovascular diseases represent a major health concern worldwide with few therapy options for ischemic injuries due to the limited regeneration potential of affected cardiomyocytes. Innovative cell replacement approaches could facilitate efficient regenerative therapy. However, despite extensive attempts to expand primary human cells in vitro, present technological limitations and the lack of human donors have so far prevented their broad clinical use. Cell xenotransplantation might provide an ethically acceptable unlimited source for cell replacement therapies and bridge the gap between waiting recipients and available donors. Pigs are considered the most suitable candidates as a source for xenogeneic cells and tissues due to their anatomical and physiological similarities with humans. The potential of porcine cells in the field of stem cell-based therapy and regenerative medicine is under intensive investigation. This review outlines the current progress and highlights the most promising approaches in xenogeneic cell therapy with a focus on the cardiovascular system.

scholarly journals Exosomes derived from three-dimensional cultured human umbilical cord mesenchymal stem cells ameliorate pulmonary fibrosis in a mouse silicosis model

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Chunjie Xu ◽  
Jing Zhao ◽  
Qiuyue Li ◽  
Lin Hou ◽  
Yan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pulmonary Fibrosis ◽  
Umbilical Cord ◽  
Three Dimensional ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Promising Alternative ◽  
Cell Based Therapy

Abstract Background Silicosis is an occupational respiratory disease caused by long-term excessive silica inhalation, which is most commonly encountered in industrial settings. Unfortunately, there is no effective therapy to delay and cure the progress of silicosis. In the recent years, stem cell therapy has emerged as an attractive tool against pulmonary fibrosis (PF) owing to its unique biological characteristics. However, the direct use of stem cells remains limitation by many risk factors for therapeutic purposes. The exclusive utility of exosomes secreted from stem cells, rather than cells, has been considered a promising alternative to overcome the limitations of cell-based therapy while maintaining its advantages. Methods and results In this study, we first employed a three-dimensional (3D) dynamic system to culture human umbilical cord mesenchymal stem cell (hucMSC) spheroids in a microcarrier suspension to yield exosomes from serum-free media. Experimental silicosis was induced in C57BL/6J mice by intratracheal instillation of a silica suspension, with/without exosomes derived from hucMSC (hucMSC-Exos), injection via the tail vein afterwards. The results showed that the gene expression of collagen I (COL1A1) and fibronectin (FN) was upregulated in the silica group as compared to that in the control group; however, this change decreased with hucMSC-Exo treatment. The value of FEV0.1 decreased in the silica group as compared to that in the control group, and this change diminished with hucMSC-Exo treatment. These findings suggested that hucMSC-Exos could inhibit silica-induced PF and regulate pulmonary function. We also performed in vitro experiments to confirm these findings; the results revealed that hucMSC-Exos decreased collagen deposition in NIH-3T3 cells exposed to silica. Conclusions Taken together, these studies support a potential role for hucMSC-Exos in ameliorating pulmonary fibrosis and provide new evidence for improving clinical treatment induced by silica.

scholarly journals Molecular Imaging of Stem Cell Transplantation for Liver Diseases: Monitoring, Clinical Translation, and Theranostics

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Ping Wang ◽  
Francesco Petrella ◽  
Luca Nicosia ◽  
Massimo Bellomi ◽  
Stefania Rizzo
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Molecular Imaging ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Clinical Studies ◽  
Liver Diseases ◽  
Cell Based Therapy ◽  
Stem Cells Transplantation

Stem cell transplantation has been investigated to rescue experimental liver failure and is promising to offer an alternative therapy to liver transplantation for liver diseases treatment. Several clinical studies in this field have been carried out, but the therapeutic benefit of this treatment is still controversial. A major obstacle to developing stem cell therapies in clinic is being able to visualize the cells in vivo. Imaging modalities allow optimization of delivery, detecting cell survival and functionality by in vivo monitoring these transplanted graft cells. Moreover, theranostic imaging is a brand new field that utilizes nanometer-scale materials to glean diagnostic insight for simultaneous treatment, which is very promising to improve stem cell-based therapy for treatment of liver diseases. The aim of this review was to summarize the various imaging tools that have been explored with advanced molecular imaging probes. We also outline some recent progress of preclinical and clinical studies of liver stem cells transplantation. Finally, we discuss theranostic imaging for stem cells transplantation for liver dysfunction and future opportunities afforded by theranostic imaging.

scholarly journals Rapid Rapamycin-Only Induced Osteogenic Differentiation of Blood-Derived Stem Cells and Their Adhesion to Natural and Artificial Scaffolds

2017 ◽  
Vol 2017 ◽  
pp. 1-12
Author(s):  
Carpentieri Arianna ◽  
Cozzoli Eliana ◽  
Acri Flavio ◽  
Ranalli Marco ◽  
Diedenhofen Giacomo ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Stem Cell ◽  
Osteogenic Differentiation ◽  
Molecular Mechanisms ◽  
Maxillofacial Surgery ◽  
Ongoing Research ◽  
Medicine Research ◽  
Cell Based Therapy

Stem cells are a centerpiece of regenerative medicine research, and the recent development of adult stem cell-based therapy systems has vigorously expanded the scope and depth of this scientific field. The regeneration of damaged and/or degraded bone tissue in orthopedic, dental, or maxillofacial surgery is one of the main areas where stem cells and their regenerative potential could be used successfully, requiring tissue engineering solutions incorporating an ideal stem cell type paired with the correct mechanical support. Our contribution to this ongoing research provides a new model of in vitro osteogenic differentiation using blood-derived stem cells (BDSCs) and rapamycin, visibly expressing typical osteogenic markers within ten days of treatment. In depth imaging studies allowed us to observe the adhesion, proliferation, and differentiation of BDSCs to both titanium and bone scaffolds. We demonstrate that BDSCs can differentiate towards the osteogenic lineage rapidly, while readily adhering to the scaffolds we exposed them to. Our results show that our model can be a valid tool to study the molecular mechanisms of osteogenesis while tailoring tissue engineering solutions to these new insights.

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