Cell-based liver therapies: past, present and future

Liver transplantation represents the standard treatment for people with an end-stage liver disease and some liver-based metabolic disorders; however, shortage of liver donor tissues limits its availability. Furthermore, whole liver replacement eliminates the possibility of using native liver as a possible target for future gene therapy in case of liver-based metabolic defects. Cell therapy has emerged as a potential alternative, as cells can provide the hepatic functions and engraft in the liver parenchyma. Various options have been proposed, including human or other species hepatocytes, hepatocyte-like cells derived from stem cells or more futuristic alternatives, such as combination therapies with different cell types, organoids and cell–biomaterial combinations. In this review, we aim to give an overview of the cell therapies developed so far, highlighting preclinical and/or clinical achievements as well as the limitations that need to be overcome to make them fully effective and safe for clinical applications. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.

Download Full-text

Cell-Based Therapies for Heart Failure

Frontiers in Pharmacology ◽

10.3389/fphar.2021.641116 ◽

2021 ◽

Vol 12 ◽

Author(s):

Antonio Carlos Campos de Carvalho ◽

Tais H. Kasai-Brunswick ◽

Adriana Bastos Carvalho

Keyword(s):

Heart Failure ◽

Heart Diseases ◽

Therapeutic Option ◽

Cell Types ◽

World Population ◽

Future Perspectives ◽

Cell Therapies ◽

Ischemic Heart Diseases ◽

Efficacious Treatment ◽

Different Cell Types

Heart failure has reached epidemic proportions with the advances in cardiovascular therapies for ischemic heart diseases and the progressive aging of the world population. Efficient pharmacological therapies are available for treating heart failure, but unfortunately, even with optimized therapy, prognosis is often poor. Their last therapeutic option is, therefore, a heart transplantation with limited organ supply and complications related to immunosuppression. In this setting, cell therapies have emerged as an alternative. Many clinical trials have now been performed using different cell types and injection routes. In this perspective, we will analyze the results of such trials and discuss future perspectives for cell therapies as an efficacious treatment of heart failure.

Download Full-text

Modulation of In Vivo Migratory Function of α2β1 Integrin in Mouse Liver

Molecular Biology of the Cell ◽

10.1091/mbc.8.10.1863 ◽

1997 ◽

Vol 8 (10) ◽

pp. 1863-1875 ◽

Cited By ~ 30

Author(s):

Wai-chi Ho ◽

Christine Heinemann ◽

Dolores Hangan ◽

Shashi Uniyal ◽

Vincent L. Morris ◽

...

Keyword(s):

Mouse Liver ◽

Cell Movement ◽

Liver Parenchyma ◽

Cell Types ◽

Optimal Level ◽

Matrix Proteins ◽

Different Cell Types ◽

Α2β1 Integrin

We report herein that expression of α2β1 integrin increased human erythroleukemia K562 transfectant (KX2C2) cell movement after extravasation into liver parenchyma. In contrast, a previous study demonstrated that α2β1 expression conferred a stationary phenotype to human rhabdomyosarcoma RD transfectant (RDX2C2) cells after extravasation into the liver. We therefore assessed the adhesive and migratory function of α2β1 on KX2C2 and RDX2C2 cells using a α2β1-specific stimulatory monoclonal antibody (mAb), JBS2, and a blocking mAb, BHA2.1. In comparison with RDX2C2 cells, KX2C2 were only weakly adherent to collagen and laminin. JBS2 stimulated α2β1-mediated interaction of KX2C2 cells with both collagen and laminin resulting in increases in cell movement on both matrix proteins. In the presence of Mn2+, JBS2-stimulated adhesion on collagen beyond an optimal level for cell movement. In comparison, an increase in RDX2C2 cell movement on collagen required a reduction in its adhesive strength provided by the blocking mAb BHA2.1. Consistent with these in vitro findings, in vivo videomicroscopy revealed that α2β1-mediated postextravasation cell movement of KX2C2 cells in the liver tissue could also be stimulated by JBS2. Thus, results demonstrate that α2β1 expression can modulate postextravasation cell movement by conferring either a stationary or motile phenotype to different cell types. These findings may be related to the differing metastatic activities of different tumor cell types.

Download Full-text

Isolation and cryopreservation of adipose tissue derived stem cells from different adipose tissues in obese patients

Journal of Morphological Sciences ◽

10.4322/jms.104717 ◽

2017 ◽

Vol 34 (03) ◽

pp. 168-172

Author(s):

D. Freitas ◽

A. Aguiar ◽

F. Janz ◽

F. Milléo ◽

G. Favero

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Adult Stem Cells ◽

Cell Types ◽

Obese Patients ◽

Cell Therapies ◽

Enzymatic Dissociation ◽

Clinical Investigations ◽

Different Cell Types ◽

Subcutaneous Adipose

Abstract Introduction: Adult stem cells (ASCs) are a population of tissue-resident cells that have the capacity for self-renewal and differentiation into different cell types with potential for cell therapies. New approaches for ASCs isolation, including many tissue sources and new protocols that are more effective and less expensive are under investigation. Thus this work aim is to isolate, maintain in cell culture and evaluate cryopreservation protocols for adipose derived stem cells (ADSCs) from different tissues such as subcutaneous adipose tissue, visceral mesenteric and omental visceral taken from the same individual. Material and Methods: The techniques of mechanical and enzymatic dissociation were used, in order to investigate the most appropriated method to ADSCs isolation. Dimethylsulfoxide (DMSO) and dimethylformamide (DMF) in different concentrations were tested as cryoprotectors in 24, 48 and 72 hours thawing protocols. The samples were collected from obese patients with associated diseases undergoing bariatric surgery, between 30 to 45 years old. Results: Among 10 collected samples it was possible to measure cell viability from 4 patients. The higher cell rate was obtained from the visceral tissue of omentum. Conclusion: DMSO was the more efficient cryopreservant for this condition. This adipose tissue source could be explored for ADSCs isolation and future clinical investigations.

Download Full-text

The sorting out of embryonic cells in monolayer, the differential adhesion hypothesis and the non-specificity of cell adhesion

Journal of Cell Science ◽

10.1242/jcs.38.1.249 ◽

1979 ◽

Vol 38 (1) ◽

pp. 249-266

Author(s):

A. Nicol ◽

D.R. Garrod

Keyword(s):

Corneal Epithelium ◽

Liver Parenchyma ◽

Cell Types ◽

Limb Bud ◽

The Other ◽

Embryonic Cells ◽

Differential Adhesion ◽

Discontinuous Phase ◽

Different Cell Types ◽

Differential Adhesion Hypothesis

It has been reported previously that sorting out of chick embryonic liver parenchyma and limb bud mesenchymal cells would take place in monolayer culture. The distribution of cell types obtained (liver formed the internal, discontinuous phase) was interpreted in terms of the differential adhesion hypothesis. It was suggested that, in monolayer, liver cells were more cohesive than limb bud cells. In this paper we set out to extend the previous observations with 2 particular questions in mind: (i) Is sorting out in monolayer a general phenomenon occurring between a wider range of cell types? (ii) Can evidence be provided for or against the interpretation of results in terms of the differential adhesion hypothesis? Sorting-out experiments were conducted on circular hydrophilic islands, on an otherwise hydrophobic substratum. Under these conditions, sorting-out in monolayer was obtained with binary combinations of 4 chick embryonic tissue types: liver parenchyma, limb bud mesenchyme, pigmented epithelium of the eye and corneal epithelium. With every combination but one, the cells of one type surrounded the cells of the other type, generating what we have called a ‘circle-within-a-circle’ configuration. With the remaining combination, liver parenchyma and corneal epithelium, only localized sorting was obtained. The ‘circle-within-a-circle’ configuration is consistent with an interpretation in terms of the differential adhesion hypothesis, according to which the distribution of cells is determined by the relative strengths of cohesions between their lateral surfaces. In direct support of this is the finding from plating the different cell types at sub-confluent density on hydrophilic substrata that limb bud is the cell tye having the weakest lateral cohesion in monolayer. Limb bud surrounded the other 3 tissues on hydrophilic island. A hierachy of lateral cohesiveness between the 4 cell types has been constructed. It is unlikely that the results can be explained in terms of specific cohesion. When plated together at subconfluent density, the 3 epithelial cell types aggregate together to form mixed monolayered islands, suggesting that they share common adhesive mechanisms.

Download Full-text

Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053310 ◽

1982 ◽

Vol 40 ◽

pp. 118-119

Author(s):

U. Aebi ◽

P. Rew ◽

T.-T. Sun

Keyword(s):

Electron Microscopy ◽

Structural Organization ◽

Cell Types ◽

Structural Features ◽

Molecular Architecture ◽

The Past ◽

Keratin Filaments ◽

Different Types ◽

10 Nm Filaments ◽

Different Cell Types

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.

Download Full-text

Processing and Characterization of Recombinant von Willebrand Factor Expressed in Different Cell Types Using a Vaccinia Virus Vector

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648398 ◽

1992 ◽

Vol 67 (01) ◽

pp. 154-160 ◽

Cited By ~ 14

Author(s):

P Meulien ◽

M Nishino ◽

C Mazurier ◽

K Dott ◽

G Piétu ◽

...

Keyword(s):

Vaccinia Virus ◽

Von Willebrand Factor ◽

Human Fibroblasts ◽

Active Form ◽

Cell Types ◽

Biologically Active ◽

L Cells ◽

Von Willebrand ◽

Different Cell Types ◽

Willebrand Factor

SummaryThe cloning of the cDNA encoding von Willebrand factor (vWF) has revealed that it is synthesized as a large precursor (pre-pro-vWF) molecule and it is now clear that the prosequence or vWAgll is responsible for the intracellular multimerization of vWF. We have cloned the complete vWF cDNA and expressed it using a recombinant vaccinia virus as vector. We have characterized the structure and function of the recombinant vWF (rvWF) secreted from five different cell types: baby hamster kidney (BHK), Chinese hamster ovary (CHO), human fibroblasts (143B), mouse fibroblasts (L) and primary embryonic chicken cells. Forty-eight hours after infection, the quantity of vWF antigen found in the cell supernatant varied from 3 to 12 U/dl depending on the cell type. By SDS-agarose gel electrophoresis, the percentage of high molecular weight forms of vWF varied from 39 to 49% relative to normal plasma for BHK, CHO, 143B and chicken cells but was less than 10% for L cells. In all cell types, the two anodic subbands of each multimer were missing. The two cathodic subbands were easily detected only in BHK and L cells. By SDS-PAGE of reduced samples, pro-vWF was present in similar quantity to the fully processed vWF subunit in L cells, present in moderate amounts in BHK and CHO and in very low amounts in 143B and chicken cells. rvWF from all cells bound to collagen and to platelets in the presence of ristocetin, the latter showing a high correlation between binding efficiency and degree of multimerization. rvWF from all cells was also shown to bind to purified FVIII and in this case binding appeared to be independent of the degree of multimerization. We conclude that whereas vWF is naturally synthesized only by endothelial cells and megakaryocytes, it can be expressed in a biologically active form from various other cell types.

Download Full-text

Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster

Acta Naturae ◽

10.32607/20758251-2016-8-2-79-86 ◽

2016 ◽

Vol 8 (2) ◽

pp. 79-86 ◽

Cited By ~ 3

Author(s):

P. V. Elizar’ev ◽

D. V. Lomaev ◽

D. A. Chetverina ◽

P. G. Georgiev ◽

M. M. Erokhin

Keyword(s):

Dna Sequences ◽

Cell Types ◽

Transcription Terminator ◽

Response Elements ◽

Polycomb Response Elements ◽

The Individual ◽

Multicellular Organisms ◽

Different Cell Types ◽

Main Factor

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

Download Full-text

MAPK: A Key Player in the Development and Progression of Stroke

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666200613223018 ◽

2020 ◽

Vol 19 (4) ◽

pp. 248-256

Author(s):

Yangmin Zheng ◽

Ziping Han ◽

Haiping Zhao ◽

Yumin Luo

Keyword(s):

Ischemic Stroke ◽

Signaling Pathway ◽

Complex Disease ◽

Therapeutic Targets ◽

Cell Types ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Effective Prevention ◽

Prevention And Treatment ◽

Different Cell Types

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.

Download Full-text

Special Issue: “Bacteriophages and Biofilms”

Viruses ◽

10.3390/v13020257 ◽

2021 ◽

Vol 13 (2) ◽

pp. 257

Author(s):

Zuzanna Drulis-Kawa ◽

Barbara Maciejewska

Keyword(s):

Cell Types ◽

Special Issue ◽

Different Cell Types

Biofilms are a community of surface-associated microorganisms characterized by the presence of different cell types in terms of physiology and phenotype [...]

Download Full-text

In situ differentiation of iridophore crystallotypes underlies zebrafish stripe patterning

Nature Communications ◽

10.1038/s41467-020-20088-1 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Dvir Gur ◽

Emily J. Bain ◽

Kory R. Johnson ◽

Andy J. Aman ◽

H. Amalia Pasoili ◽

...

Keyword(s):

Skin Color ◽

Cell Types ◽

Color Pattern ◽

Single Type ◽

Sequencing Analysis ◽

X Ray Diffraction ◽

X Ray ◽

Cryogenic Scanning Electron Microscopy ◽

Different Cell Types

AbstractSkin color patterns are ubiquitous in nature, impact social behavior, predator avoidance, and protection from ultraviolet irradiation. A leading model system for vertebrate skin patterning is the zebrafish; its alternating blue stripes and yellow interstripes depend on light-reflecting cells called iridophores. It was suggested that the zebrafish’s color pattern arises from a single type of iridophore migrating differentially to stripes and interstripes. However, here we find that iridophores do not migrate between stripes and interstripes but instead differentiate and proliferate in-place, based on their micro-environment. RNA-sequencing analysis further reveals that stripe and interstripe iridophores have different transcriptomic states, while cryogenic-scanning-electron-microscopy and micro-X-ray diffraction identify different crystal-arrays architectures, indicating that stripe and interstripe iridophores are different cell types. Based on these results, we present an alternative model of skin patterning in zebrafish in which distinct iridophore crystallotypes containing specialized, physiologically responsive, organelles arise in stripe and interstripe by in-situ differentiation.

Download Full-text