Reappraisal of Human HOG and MO3.13 Cell Lines as a Model to Study Oligodendrocyte Functioning

Myelination of neuronal axons is essential for proper brain functioning and requires mature myelinating oligodendrocytes (myOLs). The human OL cell lines HOG and MO3.13 have been widely used as in vitro models to study OL (dys) functioning. Here we applied a number of protocols aimed at differentiating HOG and MO3.13 cells into myOLs. However, none of the differentiation protocols led to increased expression of terminal OL differentiation or myelin-sheath formation markers. Surprisingly, the applied protocols did cause changes in the expression of markers for early OLs, neurons, astrocytes and Schwann cells. Furthermore, we noticed that mRNA expression levels in HOG and MO3.13 cells may be affected by the density of the cultured cells. Finally, HOG and MO3.13 co-cultured with human neuronal SH-SY5Y cells did not show myelin formation under several pro-OL-differentiation and pro-myelinating conditions. Together, our results illustrate the difficulty of inducing maturation of HOG and MO3.13 cells into myOLs, implying that these oligodendrocytic cell lines may not represent an appropriate model to study the (dys)functioning of human (my)OLs and OL-linked disease mechanisms.

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Immortalized Adult Rodent Schwann Cells as In Vitro Models to Study Diabetic Neuropathy

Experimental Diabetes Research ◽

10.1155/2011/374943 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 11

Author(s):

Kazunori Sango ◽

Hiroko Yanagisawa ◽

Shizuka Takaku ◽

Emiko Kawakami ◽

Kazuhiko Watabe

Keyword(s):

Schwann Cell ◽

Diabetic Neuropathy ◽

Schwann Cells ◽

Cell Lines ◽

Polyol Pathway ◽

Mouse Cell ◽

Biological Properties ◽

In Vitro Models ◽

Adult Mice

We have established spontaneously immortalized Schwann cell lines from normal adult mice and rats and murine disease models. One of the normal mouse cell lines, IMS32, possesses some biological properties of mature Schwann cells and high proliferative activities. The IMS32 cells under hyperglycemic and/or hyperlipidemic conditions have been utilized to investigate the pathogenesis of diabetic neuropathy, especially the polyol pathway hyperactivity, glycation, increased oxidative stress, and reduced synthesis of neurotrophic factors. In addition to the mouse cell lines, our current study focuses on the characterization of a normal rat cell line, IFRS1, under normal and high glucose conditions. These Schwann cell lines can be valuable tools for exploring the detailed mechanisms leading to diabetic neuropathy and novel therapeutic approaches against that condition.

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Malignant hematopoietic cell lines: In vitro models for the study of primary mediastinal B-cell lymphomas

Leukemia Research ◽

10.1016/j.leukres.2014.11.002 ◽

2015 ◽

Vol 39 (1) ◽

pp. 18-29 ◽

Cited By ~ 8

Author(s):

Hans G. Drexler ◽

Stefan Ehrentraut ◽

Stefan Nagel ◽

Sonja Eberth ◽

Roderick A.F. MacLeod

Keyword(s):

B Cell ◽

Cell Lines ◽

In Vitro Models ◽

Hematopoietic Cell ◽

B Cell Lymphomas ◽

Hematopoietic Cell Lines

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Hepatoma Cell Cultures as In Vitro Models for the Hepatotoxicity of Xenobiotics

Alternatives to Laboratory Animals ◽

10.1177/026119298801600108 ◽

1988 ◽

Vol 16 (1) ◽

pp. 32-37

Author(s):

Margherita Ferro ◽

Anna Maria Bassi ◽

Giorgio Nanni

Keyword(s):

Cell Lines ◽

Cell Cultures ◽

Membrane Lipids ◽

Hepatoma Cell ◽

Positive Control ◽

In Vitro Models ◽

Low Concentrations ◽

Formation Efficiency ◽

Dose Dependent

Two hepatoma cell cultures were examined as in vitro models to be used in genotoxicity and cytotoxicity tests without the addition of bioactivating enzymes. The MH1C1, and HTC hepatoma lines were used in this study to establish their sensitivity to a number of xenobiotics, namely, cyclophosphamide (CP), the classical positive control in bioactivation tests; benzaldehyde (BA), a short-chain aldehyde; and 4-hydroxynonenal (HNE), a major toxic end-product of the peroxidative degradation of cell membrane lipids. As a first approach, we compared the following cytotoxicity tests: release of lactate dehydrogenase (LDH), and colony formation efficiency (CF). Colony-forming cells were exposed to the drugs according to different procedures, before or after the anchorage phase. The leakage of LDH into the medium following exposure of both cell lines to HNE, CP and BA for up to 24 hours was found not to be a good index of cytotoxicity. A better indicator of cytotoxicity was CF, as evaluated by exposure of the cells 24 hours after seeding. The effects were detectable at very low concentrations, corresponding to 10, 90 and 100μM for HNE, CP and BA, respectively. The impairment of CF efficiency was dose-dependent and time-dependent, and several differences between the two cell lines were observed.

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The Current Challenges for Drug Discovery in CNS Remyelination

International Journal of Molecular Sciences ◽

10.3390/ijms22062891 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2891

Author(s):

Sonia Balestri ◽

Alice Del Giovane ◽

Carola Sposato ◽

Marta Ferrarelli ◽

Antonella Ragnini-Wilson

Keyword(s):

Drug Screening ◽

Myelin Sheath ◽

Time Window ◽

In Vitro Models ◽

Adult Brain ◽

Pharmacological Intervention ◽

Cellular Models ◽

New Findings ◽

Myelin Injury

The myelin sheath wraps around axons, allowing saltatory currents to be transmitted along neurons. Several genetic, viral, or environmental factors can damage the central nervous system (CNS) myelin sheath during life. Unless the myelin sheath is repaired, these insults will lead to neurodegeneration. Remyelination occurs spontaneously upon myelin injury in healthy individuals but can fail in several demyelination pathologies or as a consequence of aging. Thus, pharmacological intervention that promotes CNS remyelination could have a major impact on patient’s lives by delaying or even preventing neurodegeneration. Drugs promoting CNS remyelination in animal models have been identified recently, mostly as a result of repurposing phenotypical screening campaigns that used novel oligodendrocyte cellular models. Although none of these have as yet arrived in the clinic, promising candidates are on the way. Many questions remain. Among the most relevant is the question if there is a time window when remyelination drugs should be administrated and why adult remyelination fails in many neurodegenerative pathologies. Moreover, a significant challenge in the field is how to reconstitute the oligodendrocyte/axon interaction environment representative of healthy as well as disease microenvironments in drug screening campaigns, so that drugs can be screened in the most appropriate disease-relevant conditions. Here we will provide an overview of how the field of in vitro models developed over recent years and recent biological findings about how oligodendrocytes mature after reactivation of their staminal niche. These data have posed novel questions and opened new views about how the adult brain is repaired after myelin injury and we will discuss how these new findings might change future drug screening campaigns for CNS regenerative drugs.

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Leukemia cell lines: In vitro models for the study of acute promyelocytic leukemia

Leukemia Research ◽

10.1016/0145-2126(95)00036-n ◽

1995 ◽

Vol 19 (10) ◽

pp. 681-691 ◽

Cited By ~ 70

Author(s):

H.G. Drexler ◽

H. Quentmeier ◽

R.A.F. MacLeod ◽

C.C. Uphoff ◽

Z.-B. Hu

Keyword(s):

Acute Promyelocytic Leukemia ◽

Cell Lines ◽

Leukemia Cell ◽

In Vitro Models ◽

Promyelocytic Leukemia ◽

Leukemia Cell Lines

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Malignant hematopoietic cell lines: in vitro models for the study of anaplastic large-cell lymphoma

Leukemia ◽

10.1038/sj.leu.2403465 ◽

2004 ◽

Vol 18 (10) ◽

pp. 1569-1571 ◽

Cited By ~ 10

Author(s):

H G Drexler ◽

R A F MacLeod

Keyword(s):

Cell Lines ◽

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Large Cell ◽

In Vitro Models ◽

Hematopoietic Cell ◽

Large Cell Lymphoma ◽

Hematopoietic Cell Lines

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34 LIFESPAN AND CHROMOSOMAL STABILITY OF BOVINE AND PORCINE FETAL FIBROBLAST CELLS CULTURED IN VITRO

Reproduction Fertility and Development ◽

10.1071/rdv17n2ab34 ◽

2005 ◽

Vol 17 (2) ◽

pp. 167 ◽

Cited By ~ 2

Author(s):

A.M. Giraldo ◽

J.W. Lynn ◽

C.E. Pope ◽

R.A. Godke ◽

K.R. Bondioli

Keyword(s):

Cell Lines ◽

Cultured Cells ◽

Culture Conditions ◽

Cycle Duration ◽

Fibroblast Cells ◽

Proliferative Capacity ◽

Chromosomal Stability ◽

Fetal Fibroblasts ◽

Fetal Bovine

The low efficiency of nuclear transfer (NT) has been related to factors such as mitochondria heteroplasmy, failure of genomic activation, and asynchrony between the donor karyoplast and recipient cytoplast. Few studies have characterized donor cell lines in terms of proliferative capacity and chromosomal stability. It is known that suboptimal culture conditions can induce chromosomal abnormalities, and the use of aneuploid donor cells during NT can lead to a high incidence of abnormal cloned embryos (Giraldo et al. 2004 Reprod. Fertil. Dev. 16, 124 abst). The purpose of this study was to determine the lifespan and chromosomal stability of bovine and porcine fetal cells. Four bovine and four porcine fibroblast cells lines were established from 50-day and 40-day fetuses, respectively. Cells were cultured in DMEM medium supplemented with 10% fetal bovine serum and 1% penicillin and streptomycin at 37°C in 5% CO2. Each cell line was passaged to senescence. Total population doublings (PDs) and cell cycle duration were calculated. To determine the chromosome numbers at different PDs, cells were synchronized in metaphase, fixed, and stained. ANOVA and chi-square tests were used to analyze differences in PDs and proportion of aneuploid cells between cell lines, respectively (P < 0.05). The results show that proliferative capacity was not different between cell lines derived from the same species. Cell lines derived from bovine and porcine fetuses had different in vitro lifespans (33 PDs vs. 42 PDs, respectively; P < 0.05). The mean length of the cell cycles for both bovine and porcine fetal fibroblasts was ∼28 h. The percentage of aneupliod cells in both bovine and porcine fetal cell lines increased progressively with duration of culture (see Table) and was high throughout the study. The proliferative capacity of cultured cells was similar within individuals of the same species, but growth characteristics differed between fetal bovine and porcine cell lines. The progressive increase of aneuploid cells could be due to suboptimal culture conditions or unusual chromosome instability in the particular fetuses used. These data demonstrate the importance of determining chromosome content and the use of cells at early passages to decrease the percentage of aneuploid reconstructed embryos and increase the efficiency of NT.

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