scholarly journals New Frontiers towards Regeneration of the Intervertebral Disc: On Progenitor Cells, Growth Factors and Biomaterials

2021 ◽  
Vol 11 (24) ◽  
pp. 11913
Author(s):  
Benjamin Gantenbein
Keyword(s):  
Intervertebral Disc ◽  
Progenitor Cells ◽  
Biomechanical Testing ◽  
Cell Types ◽  
Culture Conditions ◽  
Comprehensive Overview ◽  
Physiological Conditions ◽  
Cell Sources ◽  
Set Up

This Special Issue on intervertebral disc (IVD) regeneration focuses on novel advances in understanding the cell sources and culture conditions of various cell types, i.e., progenitor and IVD cells. The issue consists of seven articles that provide a comprehensive overview of recently applied research insights: (1) into how IVD herniation can be provoked in a controlled in vitro biomechanical testing set-up, (2) how cells can be used for IVD repair, (3) the physiological conditions of IVD cells and (4) how hyaluronic acid could be used for IVD repair, and (5) how nucleus pulposus progenitor cells (NPPCs) and mesenchymal stromal cells (MSCs) shall be cultured and expanded towards a possible cell therapy.

scholarly journals Cell Sources for Human In vitro Bone Models

2021 ◽  
Author(s):  
Sana Ansari ◽  
Keita Ito ◽  
Sandra Hofmann
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Cell Types ◽  
Medium Composition ◽  
Differentiation Potential ◽  
Osteoclast Progenitor ◽  
Proliferation And Differentiation ◽  
Cell Sources

Abstract Purpose of Review One aim in bone tissue engineering is to develop human cell-based, 3D in vitro bone models to study bone physiology and pathology. Due to the heterogeneity of cells among patients, patient’s own cells are needed to be obtained, ideally, from one single cell source. This review attempts to identify the appropriate cell sources for development of such models. Recent Findings Bone marrow and peripheral blood are considered as suitable sources for extraction of osteoblast/osteocyte and osteoclast progenitor cells. Recent studies on these cell sources have shown no significant differences between isolated progenitor cells. However, various parameters such as medium composition affect the cell’s proliferation and differentiation potential which could make the peripheral blood-derived stem cells superior to the ones from bone marrow. Summary Peripheral blood can be considered a suitable source for osteoblast/osteocyte and osteoclast progenitor cells, being less invasive for the patient. However, more investigations are needed focusing on extraction and differentiation of both cell types from the same donor sample of peripheral blood.

scholarly journals Induction and Maturation of Hepatocyte-Like Cells In Vitro: Focus on Technological Advances and Challenges

2021 ◽  
Vol 9 ◽  
Author(s):  
Ye Xie ◽  
Jia Yao ◽  
Weilin Jin ◽  
Longfei Ren ◽  
Xun Li
Keyword(s):  
Genetic Manipulation ◽  
Toxicity Testing ◽  
Basic Research ◽  
Drug Approval ◽  
Cell Types ◽  
Comprehensive Overview ◽  
Technological Advances ◽  
Degree Of Differentiation

Limited by the poor proliferation and restricted sources of adult hepatocytes, there is an urgent need to find substitutes for proliferation and cultivation of mature hepatocytes in vitro for use in disease treatment, drug approval, and toxicity testing. Hepatocyte-like cells (HLCs), which originate from undifferentiated stem cells or modified adult cells, are considered good candidates because of their advantages in terms of cell source and in vitro expansion ability. However, the majority of induced HLCs are in an immature state, and their degree of differentiation is heterogeneous, diminishing their usability in basic research and limiting their clinical application. Therefore, various methods have been developed to promote the maturation of HLCs, including chemical approaches, alteration of cell culture systems, and genetic manipulation, to meet the needs of in vivo transplantation and in vitro model establishment. This review proposes different cell types for the induction of HLCs, and provide a comprehensive overview of various techniques to promote the generation and maturation of HLCs in vitro.

scholarly journals Expansion of Human Pluripotent Stem Cell-derived Early Cardiovascular Progenitor Cells by a Cocktail of Signaling Factors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sadaf Vahdat ◽  
Sara Pahlavan ◽  
Elena Mahmoudi ◽  
Maryam Barekat ◽  
Hassan Ansari ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Large Scale ◽  
Culture Medium ◽  
Gene Expression Pattern ◽  
Extended Period ◽  
Scale Production ◽  
Chemical Screening ◽  
Wide Range ◽  
Cell Sources

Abstract Cardiovascular progenitor cells (CPCs) derived from human pluripotent stem cells (hPSCs) are proposed to be invaluable cell sources for experimental and clinical studies. This wide range of applications necessitates large-scale production of CPCs in an in vitro culture system, which enables both expansion and maintenance of these cells. In this study, we aimed to develop a defined and efficient culture medium that uses signaling factors for large-scale expansion of early CPCs, called cardiogenic mesodermal cells (CMCs), which were derived from hPSCs. Chemical screening resulted in a medium that contained a reproducible combination of three factors (A83-01, bFGF, and CHIR99021) that generated 1014 CMCs after 10 passages without the propensity for tumorigenicity. Expanded CMCs retained their gene expression pattern, chromosomal stability, and differentiation tendency through several passages and showed both the safety and possible cardio-protective potentials when transplanted into the infarcted rat myocardium. These CMCs were efficiently cryopreserved for an extended period of time. This culture medium could be used for both adherent and suspension culture conditions, for which the latter is required for large-scale CMC production. Taken together, hPSC-derived CMCs exhibited self-renewal capacity in our simple, reproducible, and defined medium. These cells might ultimately be potential, promising cell sources for cardiovascular studies.

scholarly journals The Rise of Retinal Organoids for Vision Research

2020 ◽  
Vol 21 (22) ◽  
pp. 8484 ◽  
Author(s):  
Kritika Sharma ◽  
Tim U. Krohne ◽  
Volker Busskamp
Keyword(s):  
Molecular Mechanisms ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Retinal Cell ◽  
Retinal Diseases ◽  
Organ Systems ◽  
Cell Sources ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases lead to irreversible blindness. Decades of research into the cellular and molecular mechanisms of retinal diseases, using either animal models or human cell-derived 2D systems, facilitated the development of several therapeutic interventions. Recently, human stem cell-derived 3D retinal organoids have been developed. These self-organizing 3D organ systems have shown to recapitulate the in vivo human retinogenesis resulting in morphological and functionally similar retinal cell types in vitro. In less than a decade, retinal organoids have assisted in modeling several retinal diseases that were rather difficult to mimic in rodent models. Retinal organoids are also considered as a photoreceptor source for cell transplantation therapies to counteract blindness. Here, we highlight the development and field’s improvements of retinal organoids and discuss their application aspects as human disease models, pharmaceutical testbeds, and cell sources for transplantations.

scholarly journals In vitro differentiation of CD34+ hematopoietic progenitor cells toward distinct dendritic cell subsets of the birbeck granule and MIIC- positive Langerhans cell and the interdigitating dendritic cell type

Blood ◽  
1996 ◽  
Vol 88 (7) ◽  
pp. 2541-2548 ◽  
Author(s):  
B Herbst ◽  
G Kohler ◽  
A Mackensen ◽  
H Veelken ◽  
P Kulmburg ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Progenitor Cells ◽  
Mhc Class Ii ◽  
Cell Function ◽  
Fluorescein Isothiocyanate ◽  
Cell Types ◽  
Birbeck Granule ◽  
Hematopoietic Growth Factors ◽  
Necrosis Factor Alpha

We have demonstrated recently that Birbeck granule-positive Langerhans cells (LC) can be derived from CD34+ peripheral blood progenitor cells in the presence of a seven-cytokine cocktail (CC7–7). Here, we show that the sequential use of early-acting hematopoietic growth factors, stem cell factor, interleukin (IL)-3, and IL-6, followed on day 8 by differentiation in the two-factor combination IL-4 plus granulocytemacrophage colony-stimulating factor (GM-CSF) (CC4GM) is more efficient and allows the cells to be arrested in the LC stage for more than 1 week while continuous maturation occurs in CC7–7. Maturation of LC to interdigitating dendritic cells (DC) could specifically be induced within 60 hours by addition of tumor necrosis factor-alpha (20 ng/mL) or lipopolysaccharide (100 ng/mL). Using LC that had been enriched to greater than 90% CD1a+ cells by an immunoaffinity column, we were able to define clear-cut differences between LC and DC that corroborate data of the respective cells derived from epithelial borders (LC) or from lymph nodes (LN) and spleen (DC). Thus, molecules and functions involved in antigen (AG) uptake and processing were highly expressed in LC, while those involved in AG presentation were at maximum in DC. LC were CD1a+2 DR+2, CD23+, CD36+, CD80-, CD86-, and CD25-, while DC were CD1a+/- DR+3, CD23-, CD36-, CD80+, CD86+2, and CD25+, CD40 and CD32 were moderately expressed and nearly unchanged on maturation, in contrast to monocyte-derived DC. Macropinocytosis of fluorescein isothiocyanate-dextran was dominant in LC, as were multilamellar major histocompatibility complex (MHC) class II compartments (MIICs), which were detected by electron microscopy. The functional dichotomy of these cell types was finally supported by testing the AG-presenting cell function for tetanus toxoid to primed autologous T-cell lines, which was optimal when cells were loaded with AG as LC and subsequently induced to become DC.

scholarly journals Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Angela Maria Cozzolino ◽  
Valeria Noce ◽  
Cecilia Battistelli ◽  
Alessandra Marchetti ◽  
Germana Grassi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Culture Method ◽  
Cell Types ◽  
Culture Conditions ◽  
Precursor Cells ◽  
Substrate Stiffness ◽  
Growth And Survival ◽  
Liver Stem Cells

In many cell types, several cellular processes, such as differentiation of stem/precursor cells, maintenance of differentiated phenotype, motility, adhesion, growth, and survival, strictly depend on the stiffness of extracellular matrix that,in vivo, characterizes their correspondent organ and tissue. In the liver, the stromal rigidity is essential to obtain the correct organ physiology whereas any alteration causes liver cell dysfunctions. The rigidity of the substrate is an element no longer negligible for the cultivation of several cell types, so that many data so far obtained, where cells have been cultured on plastic, could be revised. Regarding liver cells, standard culture conditions lead to the dedifferentiation of primary hepatocytes, transdifferentiation of stellate cells into myofibroblasts, and loss of fenestration of sinusoidal endothelium. Furthermore, standard cultivation of liver stem/precursor cells impedes an efficient execution of the epithelial/hepatocyte differentiation program, leading to the expansion of a cell population expressing only partially liver functions and products. Overcoming these limitations is mandatory for any approach of liver tissue engineering. Here we propose cell lines asin vitromodels of liver stem cells and hepatocytes and an innovative culture method that takes into account the substrate stiffness to obtain, respectively, a rapid and efficient differentiation process and the maintenance of the fully differentiated phenotype.

scholarly journals Robust and Scalable Angiogenesis Assay of Perfused 3D Human iPSC-Derived Endothelium for Anti-Angiogenic Drug Screening

2020 ◽  
Vol 21 (13) ◽  
pp. 4804
Author(s):  
Vincent van Duinen ◽  
Wendy Stam ◽  
Eva Mulder ◽  
Farbod Famili ◽  
Arie Reijerkerk ◽  
...  
Keyword(s):  
Drug Screening ◽  
Cell Formation ◽  
Cell Types ◽  
Culture Conditions ◽  
In Vitro Assays ◽  
Vegf Receptor ◽  
Screening Assay ◽  
Angiogenesis Assay

To advance pre-clinical vascular drug research, in vitro assays are needed that closely mimic the process of angiogenesis in vivo. Such assays should combine physiological relevant culture conditions with robustness and scalability to enable drug screening. We developed a perfused 3D angiogenesis assay that includes endothelial cells (ECs) from induced pluripotent stem cells (iPSC) and assessed its performance and suitability for anti-angiogenic drug screening. Angiogenic sprouting was compared with primary ECs and showed that the microvessels from iPSC-EC exhibit similar sprouting behavior, including tip cell formation, directional sprouting and lumen formation. Inhibition with sunitinib, a clinically used vascular endothelial growth factor (VEGF) receptor type 2 inhibitor, and 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), a transient glycolysis inhibitor, both significantly reduced the sprouting of both iPSC-ECs and primary ECs, supporting that both cell types show VEGF gradient-driven angiogenic sprouting. The assay performance was quantified for sunitinib, yielding a minimal signal window of 11 and Z-factor of at least 0.75, both meeting the criteria to be used as screening assay. In conclusion, we have developed a robust and scalable assay that includes physiological relevant culture conditions and is amenable to screening of anti-angiogenic compounds.

scholarly journals Wiskott-Aldrich syndrome: cellular impairments and their implication for carrier detection

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 1048-1054 ◽  
Author(s):  
JT Prchal ◽  
AJ Carroll ◽  
JF Prchal ◽  
WM Crist ◽  
HW Skalka ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cell Types ◽  
Peripheral Blood Cell ◽  
Carrier Detection ◽  
Wiskott Aldrich Syndrome ◽  
Cultured Skin ◽  
In Cis ◽  
Hemopoietic System ◽  
Hemopoietic Progenitor

Abstract A family in which two male siblings were affected with Wiskott-Aldrich syndrome (WAS) was studied using G-6-PD isoenzymes as an X-linked marker in order to investigate the nature of cellular abnormalities. Isolated peripheral blood cell types from the doubly heterozygous mother of the affected males seemingly failed to express the G-6-PD allele in cis position with the WAS allele while her cultured skin fibroblasts expressed both G-6-PD alleles. Additionally, a histogram analysis of platelet size revealed a single population of abnormally small platelets in the affected propositus, whereas the heterozygous mother had no appreciable small platelet subpopulation. In vitro culture of hemopoietic progenitor cells of the heterozygous mother showed that the majority of progenitor cells did not express the WAS allele. However, a small number of cells expressing the G-6-PD type linked with the WAS allele were detected. The proportion of the latter progenitors was significantly higher among more primitive progenitors (those giving rise to later appearing colonies). This observation suggests that selection against cells expressing the Wiskott-Aldrich defect takes place in the hemopoietic system of the heterozygous female and offers a possible means of carrier detection in some women. Linkage studies in this family revealed one example of probable recombination between the loci for WAS and G-6-PD among three informative subjects, suggesting that these two loci may not be closely linked on the X- chromosome.

Development and regeneration in the central nervous system

1990 ◽  
Vol 327 (1239) ◽  
pp. 127-143 ◽  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Types ◽  
The Central Nervous System

As part of our attempts to understand principles that underly organism development, we have been studying the development of the rat optic nerve. This simple tissue is composed of three glial cell types derived from two distinct cellular lineages. Type-1 astrocytes appear to be derived from a monopotential neuroepithelial precursor, whereas type-2 astrocytes and oligodendrocytes are derived from a common oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. Type-1 astrocytes modulate division and differentiation of O-2A progenitor cells through secretion of platelet-derived growth factor, and can themselves be stimulated to divide by peptide mitogens and through stimulation of neurotransmitter receptors. In vitro analysis indicates that many dividing O-2A progenitors derived from optic nerves of perinatal rats differentiate symmetrically and clonally to give rise to oligodendrocytes, or can be induced to differentiate into type-2 astrocytes. O-2A perinatal progenitors can also differentiate to form a further O-2A lineage cell, the O-2A adult progenitor, which has properties specialized for the physiological requirements of the adult nervous system. In particular, O-2A adult progenitors have many of the features of stem cells, in that they divide slowly and asymmetrically and appear to have the capacity for extended self-renewal. The apparent derivation of a slowly and asymmetrically dividing cell, with properties appropriate for homeostatic maintenance of existing populations in the mature animal, from a rapidly dividing cell with properties suitable for the rapid population and myelination of central nervous system (CNS) axon tracts during early development, offers novel and unexpected insights into the possible origin of self-renewing stem cells and also into the role that generation of stem cells may play in helping to terminate the explosive growth of embryogenesis. Moreover, the properties of O-2A adult progenitor cells are consistent with, and may explain, the failure of successful myelin repair in conditions such as multiple sclerosis, and thus seem to provide a cellular biological basis for understanding one of the key features of an important human disease.

scholarly journals Simultaneous tracking of division and differentiation from individual hematopoietic stem and progenitor cells reveals within-family homogeneity despite population heterogeneity

2019 ◽  
Author(s):  
Tamar Tak ◽  
Giulio Prevedello ◽  
Gaël Simon ◽  
Noémie Paillon ◽  
Ken R. Duffy ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
High Throughput ◽  
Common Ancestor ◽  
Single Cells ◽  
Population Level ◽  
Cell Types ◽  
Culture Conditions ◽  
Population Heterogeneity ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

AbstractThe advent of high throughput single cell methods such as scRNA-seq has uncovered substantial heterogeneity in the pool of hematopoietic stem and progenitor cells (HSPCs). A significant issue is how to reconcile those findings with the standard model of hematopoietic development, and a fundamental question is how much instruction is inherited by offspring from their ancestors. To address this, we further developed a high-throughput method that enables simultaneously determination of common ancestor, generation, and differentiation status of a large collection of single cells. Data from it revealed that while there is substantial population-level heterogeneity, cells that derived from a common ancestor were highly concordant in their division progression and share similar differentiation outcomes, revealing significant familial effects on both division and differentiation. Although each family diversifies to some extent, the overall collection of cell types observed in a population is largely composed of homogeneous families from heterogeneous ancestors. Heterogeneity between families could be explained, in part, by differences in ancestral expression of cell-surface markers that are used for phenotypic HSPC identification: CD48, SCA-1, c-kit and Flt3. These data call for a revision of the fundamental model of haematopoiesis from a single tree to an ensemble of trees from distinct ancestors where common ancestor effect must be considered. As HSPCs are cultured in the clinic before bone marrow transplantation, our results suggest that the broad range of engraftment and proliferation capacities of HSPCs could be consequences of the heterogeneity in their engrafted families, and altered culture conditions might reduce heterogeneity between families, possibly improving transplantation outcomes.

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