| Title |
Disparate Response to Methotrexate in Stem Versus Non-Stem Cells
|
|---|---|
| Published in |
Stem Cell Reviews and Reports, January 2016
|
| DOI | 10.1007/s12015-016-9645-9 |
| Pubmed ID | |
| Authors |
Olivia S. Beane, Louise E. O. Darling, Vera C. Fonseca, Eric M. Darling |
| Abstract |
Methotrexate (MTX) is a commonly used chemotherapeutic agent that kills cancer cells by binding dihydrofolate reductase (DHFR) as a competitive inhibitor. Due to its non-selectivity, MTX also impairs normal (non-cancerous) cell function and causes long-term damage to healthy tissue. These consequences have been investigated extensively in bone-derived cells due to their sensitivity to the drug. While DHFR likely plays a role in normal cell response to MTX, research in this area is limited. Moreover, how MTX sensitivity differs among cell types responsible for maintaining connective tissues is unknown. The goal of this study was to investigate the role of DHFR and subsequent nucleotide synthesis in normal cell response to MTX. We also sought to compare adverse effects of MTX among normal cell types to identify sensitive populations and resistant cell sources for regenerative procedures targeting patients undergoing chemotherapy. DHFR overexpression or exogenous amino acid + nucleoside delivery rescued normal cells from adverse MTX effects. Conversely, DHFR knockdown impaired MTX-treated adipose-derived stem cell (ASC) osteogenesis. Proliferation of ASCs and bone marrow stem cells was more resistant to MTX than that of terminally differentiated osteoblasts. However, stem cells became susceptible to the drug after beginning differentiation. These results suggest that the ability of stem cells to survive and to maintain their surrounding tissues likely depends on whether they are in a "stem" state when exposed to MTX. Therapeutic strategies that delay the differentiation of stem cells until clearance of the drug may produce more favorable outcomes in the long-term health of treated tissues. |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 26 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 5 | 19% |
| Student > Master | 4 | 15% |
| Other | 3 | 12% |
| Researcher | 3 | 12% |
| Student > Ph. D. Student | 3 | 12% |
| Other | 4 | 15% |
| Unknown | 4 | 15% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 8 | 31% |
| Medicine and Dentistry | 6 | 23% |
| Engineering | 2 | 8% |
| Agricultural and Biological Sciences | 2 | 8% |
| Psychology | 2 | 8% |
| Other | 2 | 8% |
| Unknown | 4 | 15% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 September 2016.
All research outputs
#20,656,161
of 25,373,627 outputs
Outputs from Stem Cell Reviews and Reports
#820
of 1,035 outputs
Outputs of similar age
#299,932
of 405,734 outputs
Outputs of similar age from Stem Cell Reviews and Reports
#5
of 7 outputs
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