Mesenchymal Stem Cells: Potential Precursors for Tumor Stroma and Targeted-Delivery Vehicles for Anticancer Agents

Clicks: 1
ID: 303022
2004
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal

Ranked #141 of 333 articles by views in JNCI Journal of the National Cancer Institute

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 333 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Background: High concentrations of interferon beta (IFN-β) inhibit malignant cell growth in vitro. However, the therapeutic utility of IFN-β in vivo is limited by its excessive toxicity when administered systemically at high doses. Mesenchymal stem cells (MSC) can be used to target delivery of agents to tumor cells. We tested whether MSC can deliver IFN-β to tumors, reducing toxicity. Methods: Human MSC were transduced with an adenoviral expression vector carrying the human IFN-β gene (MSC-IFN-β cells). Flow cytometry was used to measure tumor cell proliferation among in vitro co-cultures of MSC-IFN-β cells and human MDA 231 breast carcinoma cells or A375SM melanoma cells. We used a severe combined immunodeficiency mouse xenograft model (4–10 mice per group) to examine the effects of injected MSC-IFN-β cells and human recombinant IFN-β on the growth of MDA 231- and A375SM-derived pulmonary metastases in vivo and on survival. All statistical tests were two-sided. Results: Co-culture of MSC-IFN-β cells with A375SM cells or MDA 231 cells inhibited tumor cell growth as compared with growth of the tumor cells cultured alone (differences in mean percentage of control cell growth: −94.0% [95% confidence interval {CI} = −81.2% to −106.8%; P <.001] and −104.8% [95% CI = −82.1% to −127.5%; P <.001], respectively). Intravenous injection of MSC-IFN-β cells into mice with established MDA 231 or A375SM pulmonary metastases led to incorporation of MSC in the tumor architecture and, compared with untreated control mice, to prolonged mouse survival (median survival for MDA 231–injected mice: 60 and 37 days for MSC-injected and control mice, respectively [difference = 23.0 days (95% CI = 14.5 to 34.0 days; P <.001]; median survival for A375SM-injected mice: 73.5 and 30.0 days for MSC-injected and control mice, respectively [difference = 43.5 days (95% CI = 37.0 to 57.5 days; P <.001]). By contrast, intravenous injection of recombinant IFN-β did not prolong survival in the same models (median survival for MDA 231–injected mice: 41.0 and 37.0 days for IFN-β–injected and control mice, respectively [difference = 4 days, 95% CI = −5 to 10 days; P = .308]; median survival for A375SM-injected mice: 32.0 and 30.0 days for IFN-β–injected and control mice, respectively [difference = 2 days, 95% CI = 0 to 4.5 days; P = .059]). Conclusions: Injected MSC-IFN-β cells suppressed the growth of pulmonary metastases, presumably through the local production of IFN-β in the tumor microenvironment. MSC may be an effective platform for the targeted delivery of therapeutic proteins to cancer sites.
Reference Key
openalex_W2143022774 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Matus Studeny, F. Marini, Jennifer L. Dembinski, Claudia Zompetta, Maria da Graça Cabreira-Hansen, B. Nebiyou Bekele, R. E. Champlin, M. Andreeff
Journal JNCI Journal of the National Cancer Institute
Year 2004
DOI
10.1093/jnci/djh299
URL
https://doi.org/10.1093/jnci/djh299
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.