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Published on: June 13, 2018
A mesenchymal stromal cell line resistant to paclitaxel that spontaneously differentiates into osteoblast-like cells
Augusto Pessina1, Francesca Sisto, Valentina Coccè
1Department of Public Health–Microbiology–Virology, University of Milan, Via Pascal 36, 20133, Milan, Italy. augusto.pessina@unimi.it
Abstract:
The mesenchymal stromal cell line SR-4987 has been established in our laboratory from the bone marrow of BDF/1 mice. Recent information on mesenchymal stem cells biology and the need to deal with well-characterized cell lines suggest to critically consider the existent data on this cell line by updating them with new investigations on growth parameters, in vitro plasticity, and drug sensitivity to anti-cancer, anti-inflammatory, and a histone deacetylase inhibitor. SR-4987 cells show a population doubling time of 24.5 ± 5.4 h, a plating efficiency of 2.87 ± 1.19%, and under stimulation maintain only in part their multipotency by differentiating towards chondro-osteogenic lineages but not into adipogenic. Surprisingly, these mesenchymal stromal cells differentiate spontaneously into osteoblast-like cells and this is significantly stimulated by valproic acid. SR-4987 cells show a dramatic resistance to paclitaxel (PTX) with a resistance index of 39.6 times (evaluated versus MOLT-4 leukemia) and of 68.2 (versus HT-29 colorectal carcinoma). SR-4987 resistance is reversed by verapamil and correlates with high expression of P-glycoprotein that is down-modulated by PTX. Taken together, our results indicated that SR-4987 line is a very interesting cell model useful to investigate both drug sensitivity resistance and physiopathological aspects related to mesenchymal cell function.
Insights
The SR-4987 mesenchymal stromal cell line exhibits partial multipotency and significant resistance to paclitaxel, a characteristic reversed by verapamil. This cell line is valuable for studying drug resistance and mesenchymal cell functions.
Area of Science:
- Cell Biology
- Pharmacology
- Biotechnology
Background:
- Mesenchymal stromal cells (MSCs) are critical for tissue repair and regeneration.
- Well-characterized MSC cell lines are essential for reliable research.
- The SR-4987 cell line, derived from BDF/1 mouse bone marrow, requires updated characterization.
Purpose of the Study:
- To re-evaluate the SR-4987 mesenchymal stromal cell line.
- To investigate its growth parameters, in vitro plasticity, and drug sensitivity.
- To assess its potential as a model for drug resistance and mesenchymal cell function.
Main Methods:
- Characterization of SR-4987 cell growth kinetics (doubling time, plating efficiency).
- Assessment of in vitro differentiation potential towards chondro-osteogenic and adipogenic lineages.
- Evaluation of drug sensitivity to anti-cancer agents (paclitaxel), anti-inflammatory drugs, and a histone deacetylase inhibitor (valproic acid).
- Analysis of drug resistance mechanisms, including P-glycoprotein expression and modulation by verapamil.
Main Results:
- SR-4987 cells have a population doubling time of 24.5 ± 5.4 h and plating efficiency of 2.87 ± 1.19%.
- The cells partially maintain multipotency, differentiating towards chondro-osteogenic lineages but not adipogenic.
- Spontaneous differentiation into osteoblast-like cells was observed and stimulated by valproic acid.
- SR-4987 cells exhibit high resistance to paclitaxel (resistance index 39.6–68.2), which is reversed by verapamil and linked to high P-glycoprotein expression.
Conclusions:
- The SR-4987 cell line is a valuable model for studying mesenchymal cell biology.
- Its significant drug resistance, particularly to paclitaxel, makes it useful for investigating resistance mechanisms.
- The line's response to valproic acid suggests potential applications in studying epigenetic modulation in mesenchymal cells.
