scholarly journals Evolving Cell-Based and Cell-Free Clinical Strategies for Treating Severe Human Liver Diseases

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 386 ◽  
Author(s):  
Viviana Cernigliaro ◽  
Rossella Peluso ◽  
Beatrice Zedda ◽  
Lorenzo Silengo ◽  
Emanuela Tolosano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Transplantation ◽  
Extracellular Vesicles ◽  
Liver Diseases ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Hepatic Function ◽  
Bioactive Molecules ◽  
Cell Based Therapy ◽  
End Stage

Liver diseases represent a major global health issue, and currently, liver transplantation is the only viable alternative to reduce mortality rates in patients with end-stage liver diseases. However, scarcity of donor organs and risk of recidivism requiring a re-transplantation remain major obstacles. Hence, much hope has turned towards cell-based therapy. Hepatocyte-like cells obtained from embryonic stem cells or adult stem cells bearing multipotent or pluripotent characteristics, as well as cell-based systems, such as organoids, bio-artificial liver devices, bioscaffolds and organ printing are indeed promising. New approaches based on extracellular vesicles are also being investigated as cell substitutes. Extracellular vesicles, through the transfer of bioactive molecules, can modulate liver regeneration and restore hepatic function. This review provides an update on the current state-of-art cell-based and cell-free strategies as alternatives to liver transplantation for patients with end-stage liver diseases.

scholarly journals In VitroandIn VivoHepatic Differentiation of Adult Somatic Stem Cells and Extraembryonic Stem Cells for Treating End Stage Liver Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Chenxia Hu ◽  
Lanjuan Li
Keyword(s):  
Stem Cells ◽  
Liver Tissue ◽  
Liver Diseases ◽  
Embryonic Stem ◽  
Somatic Stem Cells ◽  
Hepatic Differentiation ◽  
Short Supply ◽  
End Stage ◽  
Promising Source

The shortage of liver donors is a major handicap that prevents most patients from receiving liver transplantation and places them on a waiting list for donated liver tissue. Then, primary hepatocyte transplantation and bioartificial livers have emerged as two alternative treatments for these often fatal diseases. However, another problem has emerged. Functional hepatocytes for liver regeneration are in short supply, and they will dedifferentiate immediatelyin vitroafter they are isolated from liver tissue. Alternative stem-cell-based therapeutic strategies, including hepatic stem cells (HSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs), are more promising, and more attention has been devoted to these approaches because of the high potency and proliferation ability of the cells. This review will focus on the general characteristics and the progress in hepatic differentiation of adult somatic stem cells and extraembryonic stem cellsin vitroandin vivofor the treatment of end stage liver diseases. The hepatic differentiation of stem cells would offer an ideal and promising source for cell therapy and tissue engineering for treating liver diseases.

scholarly journals Therapeutic Implications of Mesenchymal Stem Cells in Liver Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Maria Ausiliatrice Puglisi ◽  
Valentina Tesori ◽  
Wanda Lattanzi ◽  
Anna Chiara Piscaglia ◽  
Giovanni Battista Gasbarrini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Diseases ◽  
Inflammatory Responses ◽  
Therapeutic Effects ◽  
Therapeutic Implications ◽  
Hepatic Cells ◽  
Cell Based Therapy ◽  
Potential Benefits ◽  
End Stage

Mesenchymal stem cells (MSCs), represent an attractive tool for the establishment of a successful stem-cell-based therapy of liver diseases. A number of different mechanisms contribute to the therapeutic effects exerted by MSCs, since these cells can differentiate into functional hepatic cells and can also produce a series of growth factors and cytokines able to suppress inflammatory responses, reduce hepatocyte apoptosis, regress liver fibrosis, and enhance hepatocyte functionality. To date, the infusion of MSCs or MSC-conditioned medium has shown encouraging results in the treatment of fulminant hepatic failure and in end-stage liver disease in experimental settings. However, some issues under debate hamper the use of MSCs in clinical trials. This paper summarizes the biological relevance of MSCs and the potential benefits and risks that can result from translating the MSC research to the treatment of liver diseases.

scholarly journals Recent Progress in Stem Cell Modification for Cardiac Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-22 ◽  
Author(s):  
Heiko Lemcke ◽  
Natalia Voronina ◽  
Gustav Steinhoff ◽  
Robert David
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Cell Delivery ◽  
Regenerative Capacity ◽  
Stem Cell Delivery ◽  
Cell Based Therapy

During the past decades, stem cell-based therapy has acquired a promising role in regenerative medicine. The application of novel cell therapeutics for the treatment of cardiovascular diseases could potentially achieve the ambitious aim of effective cardiac regeneration. Despite the highly positive results from preclinical studies, data from phase I/II clinical trials are inconsistent and the improvement of cardiac remodeling and heart performance was found to be quite limited. The major issues which cardiac stem cell therapy is facing include inefficient cell delivery to the site of injury, accompanied by low cell retention and weak effectiveness of remaining stem cells in tissue regeneration. According to preclinical and clinical studies, various stem cells (adult stem cells, embryonic stem cells, and induced pluripotent stem cells) represent the most promising cell types so far. Beside the selection of the appropriate cell type, researchers have developed several strategies to produce “second-generation” stem cell products with improved regenerative capacity. Genetic and nongenetic modifications, chemical and physical preconditioning, and the application of biomaterials were found to significantly enhance the regenerative capacity of transplanted stem cells. In this review, we will give an overview of the recent developments in stem cell engineering with the goal to facilitate stem cell delivery and to promote their cardiac regenerative activity.

scholarly journals Heterogenic transplantation of bone marrow-derived rhesus macaque mesenchymal stem cells ameliorates liver fibrosis induced by carbon tetrachloride in mouse

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4336 ◽  
Author(s):  
Xufeng Fu ◽  
Bin Jiang ◽  
Bingrong Zheng ◽  
Yaping Yan ◽  
Junfeng Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Mesenchymal Stem Cells ◽  
Carbon Tetrachloride ◽  
Liver Fibrosis ◽  
Liver Diseases ◽  
Pathological Examination ◽  
Paracrine Effects ◽  
End Stage

Liver fibrosis is a disease that causes high morbidity and has become a major health problem. Liver fibrosis can lead to the end stage of liver diseases (livercirrhosisand hepatocellularcarcinoma). Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, the shortage of organ donors, high cost of medical surgery, immunological rejection and transplantation complications severely hamper liver transplantation therapy. Mesenchymal stem cells (MSCs) have been regarded as promising cells for clinical applications in stem cell therapy in the treatment of liver diseases due to their unique multipotent differentiation capacity, immunoregulation and paracrine effects. Although liver fibrosis improvements by MSC transplantation in preclinical experiments as well as clinical trials have been reported, the in vivo fate of MSCs after transportation and their therapeutic mechanisms remain unclear. In this present study, we isolated MSCs from the bone marrow of rhesus macaques. The cells exhibited typical MSC markers and could differentiate into chondrocytes, osteocytes, and adipocytes, which were not affected by labeling with enhanced green fluorescent protein (EGFP). The harvested MSCs respond to interferon-γ stimulation and have the ability to inhibit lymphocyte proliferation in vitro. EGFP-labeled MSCs (1 × 106 cells) were transplanted into mice with carbon tetrachloride-induced liver fibrosis via tail vein injection. The ability of the heterogenic MSC infusion to ameliorate liver fibrosis in mice was evaluated by a blood plasma chemistry index, pathological examination and liver fibrosis-associated gene expression. Additionally, a small number of MSCs that homed and engrafted in the mouse liver tissues were evaluated by immunofluorescence analysis. Our results showed that the transplantation of heterogenic MSCs derived from monkey bone marrow can be used to treat liver fibrosis in the mouse model and that the paracrine effects of MSCs may play an important role in the improvement of liver fibrosis.

Immunogenicity of Stem Cells

2013 ◽  
pp. 96-111
Author(s):  
Franz Ricklefs ◽  
Sonja Schrepfer
Keyword(s):  
Stem Cells ◽  
Immune System ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Adaptive Immune System ◽  
Current Medical Research ◽  
Cell Types ◽  
Multipotent Stem Cells ◽  
Cell Based Therapy ◽  
Healthy Donors

Current medical research is focused on two particular types of stem cells, adult stem cells and embryonic stem cells. Both cell types demonstrate a tremendous potential as the source for regenerative medicine due to their paracrine and pluripotency effects, respectively. Therefore, stem cells are expected to have an enormous impact on clinical therapy. However, allogeneic approaches using “off-the-shelf” stem cells from healthy donors are the only financially and ethically feasible pathway. The long-standing assumption that stem cells are not recognized by the recipient’s immune system was recently disproved not only by our group. Therefore, specific knowledge of the immunologic properties of pluripotent and multipotent stem cells is a prerequisite for safe applications of stem cell-based therapy. This chapter will discuss the involvement of the innate and adaptive immune system and summarize state-of-the art approaches to overcome the immunological barrier.

The Use of Mesenchymal Stem Cells and their Derived Extracellular Vesicles in Cardiovascular Disease Treatment

2020 ◽  
Vol 15 (7) ◽  
pp. 623-638
Author(s):  
Saeideh Gholamzadeh Khoei ◽  
Fateme Karimi Dermani ◽  
Sara Malih ◽  
Nashmin Fayazi ◽  
Mohsen Sheykhhasan
Keyword(s):  
Cardiovascular Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Adult Stem Cells ◽  
Heart Diseases ◽  
Therapeutic Option ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Cellular Source

Background: Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the major cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treatment. Stem cell-based therapies, as a regeneration strategy, cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. Methods: In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. Results: MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. Conclusions: Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.

Mini Review; Differentiation of Human Pluripotent Stem Cells into Oocytes

2020 ◽  
Vol 15 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Gaifang Wang ◽  
Maryam Farzaneh
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cells ◽  
Human Oocyte ◽  
Differentiation Potential ◽  
Cell Lineages ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.

scholarly journals Epigenetic Regulation of Mesenchymal Stem Cells: A Focus on Osteogenic and Adipogenic Differentiation

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Chad M. Teven ◽  
Xing Liu ◽  
Ning Hu ◽  
Ni Tang ◽  
Stephanie H. Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Epigenetic Regulation ◽  
Adult Stem Cells ◽  
Es Cells ◽  
Adipogenic Differentiation ◽  
Embryonic Stem ◽  
Cell Types ◽  
Differentiation Potential ◽  
Msc Differentiation

Stem cells are characterized by their capability to self-renew and terminally differentiate into multiple cell types. Somatic or adult stem cells have a finite self-renewal capacity and are lineage-restricted. The use of adult stem cells for therapeutic purposes has been a topic of recent interest given the ethical considerations associated with embryonic stem (ES) cells. Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Owing to their ease of isolation and unique characteristics, MSCs have been widely regarded as potential candidates for tissue engineering and repair. While various signaling molecules important to MSC differentiation have been identified, our complete understanding of this process is lacking. Recent investigations focused on the role of epigenetic regulation in lineage-specific differentiation of MSCs have shown that unique patterns of DNA methylation and histone modifications play an important role in the induction of MSC differentiation toward specific lineages. Nevertheless, MSC epigenetic profiles reflect a more restricted differentiation potential as compared to ES cells. Here we review the effect of epigenetic modifications on MSC multipotency and differentiation, with a focus on osteogenic and adipogenic differentiation. We also highlight clinical applications of MSC epigenetics and nuclear reprogramming.

scholarly journals Human Adult Stem Cells Maintain a Constant Phenotype Profile Irrespective of Their Origin, Basal Media, and Long Term Cultures

2015 ◽  
Vol 2015 ◽  
pp. 1-29 ◽  
Author(s):  
Indumathi Somasundaram ◽  
Rashmi Mishra ◽  
Harikrishnan Radhakrishnan ◽  
Rajkumar Sankaran ◽  
Venkata Naga Srikanth Garikipati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Expression Profiles ◽  
Subcutaneous Fat ◽  
Adult Stem Cell ◽  
Phenotypic Marker ◽  
Human Adult ◽  
Cell Based Therapy ◽  
Basal Media

The study aims to identify the phenotypic marker expressions of different human adult stem cells derived from, namely, bone marrow, subcutaneous fat, and omentum fat, cultured in different media, namely, DMEM-Low Glucose, Alpha-MEM, DMEM-F12 and DMEM-KO and under long term culture conditions (>P20). We characterized immunophenotype by using various hematopoietic, mesenchymal, endothelial markers, and cell adhesion molecules in the long term cultures (Passages-P1, P3, P5, P9, P12, P15, and P20.) Interestingly, data revealed similar marker expression profiles irrespective of source, basal media, and extensive culturing. This demonstrates that all adult stem cell sources mentioned in this study share similar phenotypic marker and all media seem appropriate for culturing these sources. However, a disparity was observed in the markers such as CD49d, CD54, CD117, CD29, and CD106, thereby warranting further research on these markers. Besides the aforesaid objective, it is understood from the study that immunophenotyping acts as a valuable tool to identify inherent property of each cell, thereby leading to a valuable cell based therapy.

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