Human Mesenchymal Stem Cells Are Resistant to Paclitaxel by Adopting a Non-Proliferative Fibroblastic State
Open accessAbstract
Human mesenchymal stem cell (hMSC) resistance to the apoptotic effects of chemotherapeutic drugs has been of major interest, as these cells can confer this resistance to tumor microenvironments. However, the effects of internalized chemotherapeutics upon hMSCs remain largely unexplored. In this study, cellular viability and proliferation assays, combined with different biochemical approaches, were used to investigate the effects of Paclitaxel exposure upon hMSCs. Our results indicate that hMSCs are highly resistant to the cytotoxic effects of Paclitaxel treatment, even though there was no detectable expression of the efflux pump P-glycoprotein, the usual means by which a cell resists Paclitaxel treatment. Moreover, Paclitaxel treatment induces hMSCs to adopt a non-proliferative fibroblastic state, as evidenced by changes to morphology, cellular markers, and a reduction in differentiation potential that is not directly coupled to the cytoskeletal effects of Paclitaxel. Taken together, our results show that Paclitaxel treatment does not induce apoptosis in hMSCs, but does induce quiescence and phenotypic changes.
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Both BM-MSCs and ASCs have the ability to take up certain anti-cancer agents using three main mechanisms: transporters, simple diffusion, and endocytosis.
“Both BM-MSCs and ASCs have the ability to take up certain anti-cancer agents using three main mechanisms: transporters, simple diffusion, and endocytosis.”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [111]
The Discussion (page not provided) says human MSCs internalize paclitaxel because it can diffuse across the cell membrane. It does not establish uptake by both bone-marrow MSCs and ASCs, or identify transporters and endocytosis as two additional uptake mechanisms. The Results (page not provided) discuss P-glycoprotein as a drug-resistance transporter and report that it was not detected in the treated MSCs, not that it mediates uptake. (LLM, conf=0.88)
Experimental — accuracy not yet measuredLipophilic anti-cancer agents, such as paclitaxel, are taken up by BM-MSCs and ASCs via simple diffusion.
“Lipophilic anti-cancer agents, such as paclitaxel, were taken up by BM-MSCs and ASCs via a simple diffusion [109,111].”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [111]
The Discussion (page not available in our copy) says hMSCs internalize paclitaxel because its lipophilic nature allows easy diffusion across the cell membrane. It does not establish this uptake mechanism for adipose-derived stem cells (ASCs) or for lipophilic anticancer agents generally. (LLM, conf=0.88)
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- Authors
- Bosco, D. B., Kenworthy, R., Zorio, D. A. R., & Sang, Q.-X. A.
- Affiliations
- Florida State University (US)
- Corresponding author
- Zorio, Diego A. R.
- Sang, Qing-Xiang Amy
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-06-01
- Volume
- 10
- Issue
- 6
- Pages
- e0128511
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4452335
- OpenAlex
- W639465351
- Cited by
- 50
- References
- 55
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 8 · 2017: 5 · 2015: 2
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Florida State University
- Tulane University
- Sun Yat-sen University
- Sun Yat-sen University Cancer Center
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- human mesenchymal stem cells, paclitaxel, drug resistance, quiescence, P-glycoprotein, apoptosis, differentiation potential, cytoskeleton, tumor microenvironment, chemotherapy
- MeSH terms
- Antineoplastic Agents, Phytogenic, Cell Differentiation, Fibroblasts, Humans, Protein Binding, Paclitaxel, Adipocytes, ATP Binding Cassette Transporter, Subfamily B, Member 1, Cell Proliferation, Mesenchymal Stem Cells
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