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Published on: June 4, 2017
Allogeneic human neural stem cells for improved therapeutic delivery to peritoneal ovarian cancer
Rachael Mooney1, Wafa Abidi2, Jennifer Batalla-Covello3,4
1City of Hope Familian Sciences 1014A, Department of Developmental and Stem Cell Biology, Beckman Research Institute at City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. rmooney@coh.org.
Background:
Immortalized, clonal HB1.F3.CD 21 human neural stem/progenitor cells (NSCs), loaded with therapeutic cargo prior to intraperitoneal (IP) injection, have been shown to improve the delivery and efficacy of therapeutic agents in pre-clinical models of stage III ovarian cancer. In previous studies, the distribution and efficacy of the NSC-delivered cargo has been examined; however, the fate of the NSCs has not yet been explored.
Methods:
To monitor NSC tropism, we used an unconventional method of quantifying endocytosed gold nanorods to overcome the weaknesses of existing cell-tracking technologies.
Results:
Here, we report efficient tumor tropism of HB1.F3.CD 21 NSCs, showing that they primarily distribute to the tumor stroma surrounding individual tumor foci within 3 h after injection, reaching up to 95% of IP metastases without localizing to healthy tissue. Furthermore, we demonstrate that these NSCs are non-tumorigenic and non-immunogenic within the peritoneal setting.
Conclusions:
Their efficient tropism, combined with their promising clinical safety features and potential for cost-effective scale-up, positions this NSC line as a practical, off-the-shelf platform to improve the delivery of a myriad of peritoneal cancer therapeutics.
Insights
Human neural stem cells (NSCs) show excellent tumor tropism for ovarian cancer metastases. These non-tumorigenic cells efficiently target peritoneal tumors, offering a promising platform for cancer therapeutics.
Area of Science:
- Oncology
- Stem Cell Biology
- Nanotechnology
Background:
- Neural stem cells (NSCs) are being explored for targeted cancer therapy.
- Previous research focused on the cargo delivered by NSCs, not the cells themselves.
- Understanding NSC fate is crucial for optimizing their therapeutic potential.
Purpose of the Study:
- To investigate the biodistribution and fate of HB1.F3.CD 21 human neural stem/progenitor cells (NSCs) after intraperitoneal injection in ovarian cancer models.
- To evaluate the tropism and safety profile of these NSCs in the peritoneal cavity.
Main Methods:
- Utilized an innovative method quantifying endocytosed gold nanorods to track NSC tropism.
- Administered immortalized, clonal HB1.F3.CD 21 human NSCs loaded with therapeutic cargo via intraperitoneal injection.
- Assessed NSC distribution, tumor targeting, and potential for tumorigenicity and immunogenicity.
Main Results:
- Demonstrated efficient tumor tropism, with NSCs primarily localizing to the tumor stroma within 3 hours post-injection.
- Achieved widespread distribution to up to 95% of intraperitoneal metastases without affecting healthy tissues.
- Confirmed that the NSCs are non-tumorigenic and non-immunogenic in the peritoneal environment.
Conclusions:
- HB1.F3.CD 21 NSCs exhibit excellent tropism for ovarian cancer peritoneal metastases.
- These NSCs possess favorable safety characteristics, including non-tumorigenicity and non-immunogenicity.
- The NSC line represents a practical, off-the-shelf platform for enhancing peritoneal cancer therapeutics delivery.
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