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.

Hepatic differentiation of pluripotent stem cells

2009 ◽  
Vol 390 (10) ◽  
Author(s):  
Komal Loya ◽  
Reto Eggenschwiler ◽  
Kinarm Ko ◽  
Malte Sgodda ◽  
Francoise André ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Ethical Issues ◽  
Es Cells ◽  
Embryonic Stem ◽  
Hepatic Differentiation ◽  
Alternative Source ◽  
Organ Specific

Abstract In regenerative medicine pluripotent stem cells are considered to be a valuable self-renewing source for therapeutic cell transplantations, given that a functional organ-specific phenotype can be acquired by in vitro differentiation protocols. Furthermore, derivatives of pluripotent stem cells that mimic fetal progenitor stages could serve as an important tool to analyze organ development with in vitro approaches. Because of ethical issues regarding the generation of human embryonic stem (ES) cells, other sources for pluripotent stem cells are intensively studied. Like in less developed vertebrates, pluripotent stem cells can be generated from the female germline even in mammals, via parthenogenetic activation of oocytes. Recently, testis-derived pluripotent stem cells were derived from the male germline. Therefore, we compared two different hepatic differentiation approaches and analyzed the generation of definitive endoderm progenitor cells and their further maturation into a hepatic phenotype using murine parthenogenetic ES cells, germline-derived pluripotent stem cells, and ES cells. Applying quantitative RT-PCR, both germline-derived pluripotent cell lines show similar differentiation capabilities as normal murine ES cells and can be considered an alternative source for pluripotent stem cells in regenerative medicine.

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.

An extracellular matrix-based culture system for generation of human pluripotent stem cell derived-hepatocytes

2020 ◽  
Vol 16 ◽  
Author(s):  
Mehdi Forouzesh ◽  
Mojgan Hosseini ◽  
Mehran Ataei ◽  
Maryam Farzaneh ◽  
Seyed Esmaeil Khoshnam
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Pluripotent Stem Cells ◽  
Liver Diseases ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
3D Culture ◽  
Hepatic Differentiation ◽  
Human Escs ◽  
Culture Methods

: Liver disease (hepatic disease) adversely affects the normal function of the liver and causes liver problems. Druginduced liver injury (DILI) can be predicted by primary human hepatocytes. However, the sources of hepatocytes for largescale drug toxicity screening are limited. To solve this problem, pluripotent stem cells (PSCs), mesenchymal stem cells (MSCs), and hepatic stem cells (HSCs) have emerged as attractive cell sources for cell-based therapies. Human PSCs including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the ability to undergo self-renewal and to differentiate into lineages of ectoderm, mesoderm, and endoderm. Human PSC can be used for generation of hepatocytes to facilitate the development of novel drugs for treatment of severe liver diseases. The therapeutic potential of PSC-derived hepatocytes for liver failure have been identified to enhance the development of chemically defined and xenogenic-free 3D culture methods. To date, several hepatic differentiation strategies and various extracellular matrix (ECM) components have been employed to produce hepatocytes or hepatic-like cells (HLCs) in vitro. In this review, we focused on the potential of Matrigel, collagen type 1, RoGel, and laminin as ECM on the differentiation and function of hESC- and hiPSC-derived hepatocytes. The hepatic differentiation of human ESCs and iPSCs would offer an ideal tool for cell therapy and liver diseases.

scholarly journals Mesenchymal Stem Cells in the Adult Human Liver: Hype or Hope?

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1127 ◽  
Author(s):  
Irina V. Kholodenko ◽  
Leonid K. Kurbatov ◽  
Roman V. Kholodenko ◽  
Garik V. Manukyan ◽  
Konstantin N. Yarygin
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Liver Tissue ◽  
Liver Diseases ◽  
Human Liver ◽  
Chronic Liver ◽  
Attractive Alternative ◽  
Short Supply

Chronic liver diseases constitute a significant economic, social, and biomedical burden. Among commonly adopted approaches, only organ transplantation can radically help patients with end-stage liver pathologies. Cell therapy with hepatocytes as a treatment for chronic liver disease has demonstrated promising results. However, quality human hepatocytes are in short supply. Stem/progenitor cells capable of differentiating into functionally active hepatocytes provide an attractive alternative approach to cell therapy for liver diseases, as well as to liver-tissue engineering, drug screening, and basic research. The application of methods generally used to isolate mesenchymal stem cells (MSCs) and maintain them in culture to human liver tissue provides cells, designated here as liver MSCs. They have much in common with MSCs from other tissues, but differ in two aspects—expression of a range of hepatocyte-specific genes and, possibly, inherent commitment to hepatogenic differentiation. The aim of this review is to analyze data regarding liver MSCs, probably another type of liver stem/progenitor cells different from hepatic stellate cells or so-called hepatic progenitor cells. The review presents an analysis of the phenotypic characteristics of liver MSCs, their differentiation and therapeutic potential, methods for isolating these cells from human liver, and discusses issues of their origin and heterogeneity. Human liver MSCs are a fascinating object of fundamental research with a potential for important practical applications.

In Vitro Hepatic Differentiation of Adult, Embryonic, Induced Pluripotent and Perinatal Stem-Cells

2020 ◽  
Keyword(s):  
Stem Cells ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Organ Transplantation ◽  
Cell Transplantation ◽  
Hepatic Differentiation ◽  
End Stage Liver Disease ◽  
Induced Pluripotent ◽  
End Stage

Globally regenerative medicine is considered as one of the rapidly growing biomedical industry have objective to substitute damaged cells. Cell transplantation is less intrusive than whole-organ transplantation, and has been used to provide an alternative for patients to whole-organ transplantation. The End-stage liver disease comprises a subgroup of patients with cirrhosis who have signs of decompensation that is irreversible with medical treatment. The only restorative therapy for severe end-stage liver disease is orthotropic liver transplantation. However, liver transplantation has several limitations such as scarcity of organ donors, immunosuppressive drugs, and several postoperative complications. Thus, cell transplantation can be used for the treatment of end stage liver disorders to decrease the mortality in acute liver failure. Therefore, stem cells can be used for cellular therapy, development of liver disease models, and tissue-engineering applications. This review involved the studies conducted on the stem cells potential of hepatic differentiation, isolated from different sources. The PubMed and Google Scholar were searched for scientific studies reported the sources of stem cells based on their origin and their potential of hepatic differentiation in-vitro by using different tools of differentiation. All the research articles were selected in which solely hepatic differentiation in combination with different tools is reported. Keywords: Adult Stem Cells, Embryonic Stem Cells, Induced Pluripotent Stem Cells, In-vitro, Mesenchymal Stem Cells.

scholarly journals Co-growth of Stem Cells With Target Tissue Culture as an Easy and Effective Method of Directed Differentiation

2021 ◽  
Vol 9 ◽  
Author(s):  
Marina Valentinovna Kovina ◽  
Tatyana Gennadievna Dyuzheva ◽  
Mikhail Evgenievich Krasheninnikov ◽  
Sergey Alexandrovich Yakovenko ◽  
Yury Mikhailovich Khodarovich
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
Cell Contact ◽  
Target Tissue ◽  
Hepatic Differentiation ◽  
Endothelial Surface ◽  
Adult Mesenchymal Stem Cells

The long-term co-culture of mouse embryonic stem cells (mESC) with rat endothelial cells (EC) was tested for contact differentiation into the endothelial lineage. Serial passaging of rat ECs mixed with mESC in ratio 10:1 resulted in the emergence of a homogeneous cell population expressing mouse endothelial surface markers CD102, CD29, CD31. Rat endothelial surface marker RECA-1 completely disappeared from the co-cultured population after 2 months of weekly passaging. Co-incubation of mESC with rat ECs without cell-to-cell contact did not result in the conversion of mESC into ECs. After co-cultivation of adult mesenchymal stem cells from human endometrium (eMSC) with pre-hepatocyte-like cells of human hepatocarcinoma Huh7 the resulting co-culture expressed mature liver markers (oval cell antigen and cytokeratin 7), none of which were expressed by any of co-cultivated cultures, thus proving that even an immature (proliferating) pre-hepatocyte-like line can induce hepatic differentiation of stem cells. In conclusion, we have developed conditions where long-term co-proliferation of embryonic or adult SC with fully or partially differentiated cells results in stem cell progeny expressing markers of target tissue. In the case of endothelial differentiation, the template population quickly disappeared from the resulted culture and the pure endothelial population of stem cell progeny emerged. This approach demonstrates the expected fate of stem cells during various in vivo SC-therapies and also might be used as an effective in vitro differentiation method to develop the pure endothelium and, potentially, other tissue types of desirable genetic background.

scholarly journals Evidence for existence of molecular stemness markers in porcine ovarian follicular granulosa cells

2019 ◽  
Vol 7 (4) ◽  
pp. 183-188 ◽  
Author(s):  
Katarzyna Stefańska ◽  
Rafał Sibiak ◽  
Greg Hutchings ◽  
Claudia Dompe ◽  
Lisa Moncrieff ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Granulosa Cells ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
In Vitro Cultivation ◽  
Stem Cell Markers ◽  
Promising Alternative ◽  
Promising Source

AbstractGranulosa cells (GCs) are important component of the follicle, a principal functional unit of the ovary. They undergo highly dynamic changes during folliculogenesis and play a vital role in oocyte’s maturation. Recently, it has been shown that GCs also exhibit stem cell properties, since they express OCT-4, Nanog, Sox-2, which are markers of pluripotency, as well as several mesenchymal stem cell markers, such as CD29, CD44, CD90, CD105, CD117 or CD166. In addition, GCs are able to differentiate towards neurogenic, chondrogenic and osteogenic lineages. Since the use of embryonic stem cells in regenerative medicine is burdened with ethical concerns and the risk of immune rejection or teratoma formation, adult stem cells are emerging as a promising alternative. GCs especially seem to provide a promising source of stem cells, since they are easily obtainable during assisted reproduction techniques. In order to better understand the genetic changes taking place in proliferating granulosa cells cultured in vitro, we isolated GCs from 40 prepubertal gilts and cultured them in vitro for 168 h. After 24, 48, 72, 96, 120, 144 and 168 h of cultivation the total RNA was extracted, reverse transcription was conducted and RT-qPCR reaction was performed. We observed that CD44, CD90 and IGF1 were upregulated after the cultivation, whereas CD105 and LIF were downregulated. Collectively, our results confirm stemness potential of porcine GCs and provide an insight into the transcriptome changes during in vitro cultivation.Running title: Molecular stemness markers in porcine granulosa cells

scholarly journals Effect of Microenvironment on Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into HepatocytesIn VitroandIn Vivo

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Gai Xue ◽  
Xiaolei Han ◽  
Xin Ma ◽  
Honghai Wu ◽  
Yabin Qin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Liver Tissue ◽  
Human Umbilical Cord ◽  
Hepatic Differentiation ◽  
Differentiation Potential ◽  
Tissue Microenvironment

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are considered to be an ideal cell source for cell therapy of many diseases. The aim of this study was to investigate the contribution of the microenvironment to the hepatic differentiation potential of hUCMSCsin vitroandin vivoand to explore their therapeutic use in acute liver injury in rats. We established a new model to simulate the liver tissue microenvironmentin vivousing liver homogenate supernatant (LHS)in vitro. This induced environment could drive hUCMSCs to differentiate into hepatocyte-like cells within 7 days. The differentiated cells expressed hepatocyte-specific markers and demonstrated hepatocellular functions. We also injected hUCMSCs into rats with CCl4-induced acute hepatic injury. The hUCMSCs were detected in the livers of recipient rats and expressed the human hepatocyte-specific markers, suggesting that hUCMSCs could differentiate into hepatocyte-like cellsin vivoin the liver tissue microenvironment. Levels of biochemistry markers improved significantly after transplantation of hUCMSCs compared with the nontransplantation group (P<0.05). In conclusion, this study demonstrated that the liver tissue microenvironment may contribute to the differentiation of hUCMSCs into hepatocytes bothin vitroandin vivo.

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