Allogeneic human neural stem cells for improved therapeutic delivery to peritoneal ovarian cancer

Stem Cell Research & Therapy

Hoi Wa Ngai¹  Linda Flores¹  Caitlyn Hyde¹  Diana Machado¹  Asma Abdul-Majid¹  Mohamed Hammad¹  Karen S. Aboody¹  Rachael Mooney¹  Jennifer Batalla-Covello²  Wafa Abidi³  Jacob Berlin³  Greg Copeland³  Thanh Dellinger⁴  Ernest Han⁴  Yanan Kang⁵ 

[1] City of Hope Familian Sciences 1014A, Department of Developmental and Stem Cell Biology, Beckman Research Institute at City of Hope, 1500 East Duarte Road, 91010, Duarte, CA, USA;City of Hope Familian Sciences 1014A, Department of Developmental and Stem Cell Biology, Beckman Research Institute at City of Hope, 1500 East Duarte Road, 91010, Duarte, CA, USA;Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute at City of Hope, 1500 East Duarte Road, 91010, Duarte, CA, USA;Department of Molecular Medicine, Beckman Research Institute at City of Hope, 1500 East Duarte Road, 91010, Duarte, CA, USA;Division of Gynecologic Surgery, Beckman Research Institute at City of Hope, 1500 East Duarte Road, 91010, Duarte, CA, USA;Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute at City of Hope, 1500 East Duarte Road, 91010, Duarte, CA, USA;Department of Molecular Medicine, Beckman Research Institute at City of Hope, 1500 East Duarte Road, 91010, Duarte, CA, USA;

关键词: Neural stem cells;    Ovarian cancer;    Peritoneal metastases;    Tumor tropism;    Cell therapy;    Drug delivery;   

DOI  :  10.1186/s13287-021-02226-8

来源: Springer

【 摘 要 】

BackgroundImmortalized, 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.MethodsTo monitor NSC tropism, we used an unconventional method of quantifying endocytosed gold nanorods to overcome the weaknesses of existing cell-tracking technologies.ResultsHere, 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 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.ConclusionsTheir 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.

【 授权许可】

CC BY