Glioblastoma Bystander Cell Therapy: Improvements in Treatment and Insights into the Therapy Mechanisms
Por:
Guerra-Rebollo, M, de Moraes, CN, Alcoholado, C, Soler-Botija, C, Sanchez-Cid, L, Vila, OF, Meca-Cortes, O, Ramos-Romero, S, Rubio, N, Becerra, J, Blanco, J and Garrido, C
Publicada:
21 dic 2018
Resumen:
A preclinical model of glioblastoma (GB) bystander cell therapy using human adipose mesenchymal stromal cells (hAMSCs) is used to address the issues of cell availability, quality, and feasibility of tumor cure. We show that a fast proliferating variety of hAMSCs expressing thymidine kinase (TK) has therapeutic capacity equivalent to that of TK-expressing hAMSCs and can be used in a multiple-inoculation procedure to reduce GB tumors to a chronically inhibited state. We also show that up to 25% of unmodified hAMSCs can be tolerated in the therapeutic procedure without reducing efficacy. Moreover, mimicking a clinical situation, tumor debut dng previous to cell therapy inhibits GB tumor growth. To understand these striking results at a cellular level, we used a bioluminescence imaging strategy and showed that tumor-implanted therapeutic cells do not proliferate, are unaffected by GCV, and spontaneously decrease to a stable leveL Moreover, using the CLARITY procedure for tridimensional visualization of fluorescent cells in transparent brains, we find therapeutic cells forming vascular-like structures that often associate with tumor cells. In vitro experiments show that therapeutic cells exposed to GCV produce cytotoxic extracellular vesicles and suggest that a similar mechanism may be responsible for the in vivo therapeutic effectiveness of TK-expressing hAMSCs.
Filiaciones:
Guerra-Rebollo, M:
Catalonian Inst Adv Chem IQAC CSIC, Cell Therapy Grp, Jordi Girona St 18-26, Barcelona 08034, Spain
Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid 28040, Spain
de Moraes, CN:
Sao Paulo State Univ, Coll Vet Med & Anim Sci, Dept Anim Reprod & Vet Radiol, UNESP, BR-18618681 Botucatu, SP, Brazil
Alcoholado, C:
Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid 28040, Spain
Univ Malaga, Biomed Res Inst Malaga IBIMA, Fac Sci, Dept Cell Biol Genet & Physiol, E-29071 Malaga, Spain
:
Hlth Sci Res Inst Germans Trias & Pujol, ICREC Res Program, Badalona 08916, Spain
Carlos III Hlth Inst, CIBER Cardiovasc, Madrid 28029, Spain
Sanchez-Cid, L:
Catalonian Inst Adv Chem IQAC CSIC, Cell Therapy Grp, Jordi Girona St 18-26, Barcelona 08034, Spain
Vila, OF:
Catalonian Inst Adv Chem IQAC CSIC, Cell Therapy Grp, Jordi Girona St 18-26, Barcelona 08034, Spain
Columbia Univ, Dept Biomed Engn, New York, NY 10032 USA
Meca-Cortes, O:
Catalonian Inst Adv Chem IQAC CSIC, Cell Therapy Grp, Jordi Girona St 18-26, Barcelona 08034, Spain
Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid 28040, Spain
Ramos-Romero, S:
Catalonian Inst Adv Chem IQAC CSIC, Cell Therapy Grp, Jordi Girona St 18-26, Barcelona 08034, Spain
Univ Barcelona, Fac Biol, Dept Cell Biol Physiol & Immunol, E-08028 Barcelona, Spain
Rubio, N:
Catalonian Inst Adv Chem IQAC CSIC, Cell Therapy Grp, Jordi Girona St 18-26, Barcelona 08034, Spain
Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid 28040, Spain
Becerra, J:
Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid 28040, Spain
Univ Malaga, Biomed Res Inst Malaga IBIMA, Fac Sci, Dept Cell Biol Genet & Physiol, E-29071 Malaga, Spain
Andalusian Ctr Nanomed & Biotechnol BIONAND, Lab Bioengn & Tissue Regenerat LABRET, Malaga 29590, Spain
Blanco, J:
Catalonian Inst Adv Chem IQAC CSIC, Cell Therapy Grp, Jordi Girona St 18-26, Barcelona 08034, Spain
Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid 28040, Spain
Garrido, C:
Catalonian Inst Adv Chem IQAC CSIC, Cell Therapy Grp, Jordi Girona St 18-26, Barcelona 08034, Spain
Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid 28040, Spain
Green Published, gold
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