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Background: Immortalized, clonal HB1.F3.CD21 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.CD21 NSCs, showing that they primarily distribute to the tumor stroma surrounding individual tumor foci within 3 hours 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.
Keywords
Neural Stem Cells, Ovarian Cancer, Peritoneal Metastases, Tumor Tropism, Cell Therapy, Drug Delivery
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CURRENT STATUS: Published
View the published article at Stem Cell Research & Therapy.
Version 2
Posted 13 Jan, 2021
No community comments so far
Editorial decision: Accept
On 10 Feb, 2021
Review #1 received
Received 13 Jan, 2021
Reviewer #1 agreed
On 06 Jan, 2021
Reviewers invited
Invitations sent on 05 Jan, 2021
Editor assigned
On 03 Jan, 2021
Submission checks complete
On 03 Jan, 2021
Editor invited
On 03 Jan, 2021
No comments provided
Editorial decision: Minor Revision
On 13 Nov, 2020
Review #2 received
Received 19 Oct, 2020
Reviewer #2 agreed
On 12 Oct, 2020
Review #1 received
Received 11 Oct, 2020
Reviewers invited
Invitations sent on 02 Oct, 2020
Reviewer #1 agreed
On 02 Oct, 2020
Editor assigned
On 13 Aug, 2020
Submission checks complete
On 12 Aug, 2020
Editor invited
On 12 Aug, 2020
First submitted
On 10 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
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A new preprint design is coming!
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See the published version of this preprint at Stem Cell Research & Therapy.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Stem Cell Research & Therapy.
Version 2
Posted 13 Jan, 2021
No community comments so far
Editorial decision: Accept
On 10 Feb, 2021
Review #1 received
Received 13 Jan, 2021
Reviewer #1 agreed
On 06 Jan, 2021
Reviewers invited
Invitations sent on 05 Jan, 2021
Editor assigned
On 03 Jan, 2021
Submission checks complete
On 03 Jan, 2021
Editor invited
On 03 Jan, 2021
No comments provided
Editorial decision: Minor Revision
On 13 Nov, 2020
Review #2 received
Received 19 Oct, 2020
Reviewer #2 agreed
On 12 Oct, 2020
Review #1 received
Received 11 Oct, 2020
Reviewers invited
Invitations sent on 02 Oct, 2020
Reviewer #1 agreed
On 02 Oct, 2020
Editor assigned
On 13 Aug, 2020
Submission checks complete
On 12 Aug, 2020
Editor invited
On 12 Aug, 2020
First submitted
On 10 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Stem Cell Research & Therapy.
Background: Immortalized, clonal HB1.F3.CD21 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.CD21 NSCs, showing that they primarily distribute to the tumor stroma surrounding individual tumor foci within 3 hours 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.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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