Developing bioinspired Three-dimensional models of brain cancer to evaluate tumor-homing neural stem cell therapy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00843989%3A_____%2F21%3AE0109080" target="_blank" >RIV/00843989:_____/21:E0109080 - isvavai.cz</a>
Result on the web
<a href="https://www.liebertpub.com/doi/10.1089/ten.tea.2020.0113" target="_blank" >https://www.liebertpub.com/doi/10.1089/ten.tea.2020.0113</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1089/ten.TEA.2020.0113" target="_blank" >10.1089/ten.TEA.2020.0113</a>
Alternative languages
Result language
angličtina
Original language name
Developing bioinspired Three-dimensional models of brain cancer to evaluate tumor-homing neural stem cell therapy
Original language description
Engineered neural stem cells (NSCs) have recently emerged as a promising therapy. Acting as a tumor-homing drug-delivery system, NSCs migrate through brain tissue to seek out primary and invasive tumor foci. NSCs can deliver therapeutic agents, such as TNF?-related apoptosis-inducing ligand, directly to the tumor and suppress glioblastoma (GBM) in murine models. While the mainstays for evaluating NSC migration and efficacy have been two-dimensional chemotaxis assays and mouse models, these low-throughput and small-scale systems limit our ability to implant and track these cells for human translation. To circumvent these challenges, we developed a three-dimensional culture system using a matrix of poly-l-lactic acid 6100 microfibers suspended in agar. These bioinspired brain matrices were used to model tumor growth, NSC migration, and efficacy of NSC therapy at small and human scale. Kinetic fluorescent imaging confirmed growth of tumors in both small and human-sized bioinspired brain matrix. Tumors proliferated 50-fold and 3-fold for GBM and human metastatic breast cancer, respectively, over 7 days. We next explored the impact of tumor location on NSC migration. When NSCs were implanted 2 mm lateral from the tumor foci, NSCs colocalized with the GBM within 7 days. In models of multifocal disease, NSCs were found to colocalize with multiple tumors, preferentially migrating to tumor foci closest to the site of NSC implantation. Lastly, therapeutic NSCs were implanted at increasing distances (0, 2, 5, or 10 mm) laterally from GBM foci to investigate the effects of distance on NSC efficacy. Serial imaging showed reduced fluorescence at tumor sites, implicating GBM apoptosis across all distances. NSCs coinjected with tumor induced a near-complete response in <10 days, while NSCs implanted 10 mm laterally from the tumor induced a near-complete response by day 30. Lastly, GBM foci were established in each hemisphere of the model and control or therapeutic NSCs were impl...
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30402 - Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction)
Result continuities
Project
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Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Tissue engineering Part A
ISSN
1937-3341
e-ISSN
1937-335X
Volume of the periodical
27
Issue of the periodical within the volume
13-14
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
857-866
UT code for WoS article
000587456300001
EID of the result in the Scopus database
2-s2.0-85110522231