TY - JOUR

T1 - Targeting brain tumors with mesenchymal stem cells in the experimental model of the orthotopic glioblastoma in rats

AU - Yudintceva, Natalia

AU - Lomert, Ekaterina

AU - Mikhailova, Natalia

AU - Tolkunova, Elena

AU - Agadzhanian, Nikol

AU - Samochernych, Konstantin

AU - Multhoff, Gabriele

AU - Timin, Grigoriy

AU - Ryzhov, Vyacheslav

AU - Deriglazov, Vladimir

AU - Mazur, Anton

AU - Shevtsov, Maxim

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/11/1

Y1 - 2021/11/1

N2 - Despite multimodal approaches for the treatment of multiforme glioblastoma (GBM) advances in outcome have been very modest indicating the necessity of novel diagnostic and therapeutic strategies. Currently, mesenchymal stem cells (MSCs) represent a promising platform for cell-based cancer therapies because of their tumor-tropism, low immunogenicity, easy accessibility, isolation procedure, and culturing. In the present study, we assessed the tumor-tropism and biodistribution of the superparamagnetic iron oxide nanoparticle (SPION)-labeled MSCs in the orthotopic model of C6 glioblastoma in Wistar rats. As shown in in vitro studies employing confocal microscopy, high-content quantitative image cytometer, and xCelligence system MSCs exhibit a high migratory capacity towards C6 glioblastoma cells. Intravenous administration of SPION-labeled MSCs in vivo resulted in intratumoral accumulation of the tagged cells in the tumor tissues that in turn significantly enhanced the contrast of the tumor when high-field magnetic resonance imaging was performed. Subsequent biodistribution studies employing highly sensitive nonlinear magnetic response measurements (NLR-M2 ) supported by histological analysis confirm the retention of MSCs in the glioblastoma. In conclusion, MSCs due to their tumor-tropism could be employed as a drug-delivery platform for future theranostic approaches.

AB - Despite multimodal approaches for the treatment of multiforme glioblastoma (GBM) advances in outcome have been very modest indicating the necessity of novel diagnostic and therapeutic strategies. Currently, mesenchymal stem cells (MSCs) represent a promising platform for cell-based cancer therapies because of their tumor-tropism, low immunogenicity, easy accessibility, isolation procedure, and culturing. In the present study, we assessed the tumor-tropism and biodistribution of the superparamagnetic iron oxide nanoparticle (SPION)-labeled MSCs in the orthotopic model of C6 glioblastoma in Wistar rats. As shown in in vitro studies employing confocal microscopy, high-content quantitative image cytometer, and xCelligence system MSCs exhibit a high migratory capacity towards C6 glioblastoma cells. Intravenous administration of SPION-labeled MSCs in vivo resulted in intratumoral accumulation of the tagged cells in the tumor tissues that in turn significantly enhanced the contrast of the tumor when high-field magnetic resonance imaging was performed. Subsequent biodistribution studies employing highly sensitive nonlinear magnetic response measurements (NLR-M2 ) supported by histological analysis confirm the retention of MSCs in the glioblastoma. In conclusion, MSCs due to their tumor-tropism could be employed as a drug-delivery platform for future theranostic approaches.

KW - Biodistribution

KW - C6 glioma

KW - Magnetic resonance imaging

KW - Mesenchymal stem cells

KW - Multiforme glioblastoma

KW - Nonlinear magnetic response

KW - Superparamagnetic iron oxide nanoparticles

KW - Targeted drug delivery

KW - IRON-OXIDE NANOPARTICLES

KW - biodistribution

KW - magnetic resonance imaging

KW - multiforme glioblastoma

KW - targeted drug delivery

KW - nonlinear magnetic response

KW - BIODISTRIBUTION

KW - THERAPY

KW - TROPISM

KW - mesenchymal stem cells

KW - superparamagnetic iron oxide nanoparticles

KW - GENERATION

UR - http://www.scopus.com/inward/record.url?scp=85118530373&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/893bab4e-2170-3505-a52d-8f4a6eaba899/

U2 - 10.3390/biomedicines9111592

DO - 10.3390/biomedicines9111592

M3 - Article

AN - SCOPUS:85118530373

VL - 9

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 11

M1 - 1592

ER -