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Rat Adipose-Derived Stromal Cells (ADSCs) Increases the Glioblastoma Growth and Decreases the Animal Survival

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Abstract

Many studies have shown that mesenchymal stromal cells (MSCs) and their secreted factors may modulate the biology of tumor cells. However, how these interactions happen in vivo remains unclear. In the present study, we investigated the effects of rat adipose-derived stromal cells (ADSCs) and their conditioned medium (ADSC-CM) in glioma tumor growth and malignancy in vivo. Our results showed that when we co-injected C6 cells plus ADSCs into the rat brains, the tumors generated were larger and the animals exhibited shorter survival, when compared with tumors of the animals that received only C6 cells or C6 cells pre-treated with ADSC-CM. We further showed that the animals that received C6 plus ADSC did not present enhanced expression of CD73 (a gene highly expressed in ADSCs), indicating that the tumor volume observed in these animals was not a mere consequence of the higher density of cells administered in this group. Finally, we showed that the animals that received C6 + ADSC presented tumors with larger necrosis areas and greater infiltration of immune cells. These results indicate that the immunoregulatory properties of ADSCs and its contribution to tumor stroma can support tumor growth leading to larger zones of necrosis, recruitment of immune cells, thus facilitating tumor progression. Our data provide new insights into the way by which ADSCs and tumor cells interact and highlight the importance of understanding the fate and roles of MSCs in tumor sites in vivo, as well as their intricate crosstalk with cancer cells.

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Acknowledgements

The authors would like to thank Giuliano Rizzotto Guimarães, Terezinha Stein and Rosalva Thereza Meurer (Laboratório de Pesquisa em Patologia, UFCSPA) for excellent technical assistance with histological analysis and M.Sc. Cristiano Rodrigues for his assistance in animal facility. The authors also gratefully acknowledge veterinarians Drs. Fernanda Bastos de Mello and Joana Fisch for animal assistance.

Funding

APSB is recipient of PNPD fellowship from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior); MRW, GL, EB and LLX are recipients of research fellowship from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico); ICI was recipient of PDJ and LRB was recipient of DTI-B fellowship from CNPq. This study was supported by CNPq, MS-SCTIE-Decit/CNPq nº 12/2018 (441575/2018-8) and MS-SCTIE-DECIT-DGITIS-CGCIS/CNPq nº 26/2020 (442586/2020–5); and by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul—Brasil (FAPERGS/CAPES 06/2018—Programa de Internacionalização da pós-graduação no RS (19/2551-0000679-9).

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Authors and Affiliations

  1. Departamento de Ciências Básicas da Saúde e Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Rua Sarmento Leite, 245, Porto Alegre, RS, CEP 90050-170, Brazil

    Isabele Cristiana Iser, Liziane Raquel Beckenkamp, Juliana Hofstatter Azambuja, Ana Paula Santin Bertoni, Elizandra Braganhol & Márcia Rosângela Wink

  2. Departamento de Ciências Básicas da Saúde e Laboratório de Pesquisa em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Porto Alegre, RS, Brazil

    Francine Luciano Rahmeier & Marilda da Cruz Fernandes

  3. Departamento de Estatística E Programa de Pós-Graduação Em Epidemiologia, Universidade Federal do Rio Grande do Sul – UFRGS, Porto Alegre, RS, Brazil

    Paula Andreghetto Bracco

  4. Departamento de Patologia E Medicina Legal, Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Porto Alegre, RS, Brazil

    Rita de Cássia Sant’Anna Alves

  5. Escola de Ciências da Saúde E da Vida, Pontifícia Universidade Católica do Rio Grande do Sul – PUCRS, Porto Alegre, RS, Brazil

    Léder Leal Xavier

  6. Departamento de Biofísica E Centro de Biotecnologia, Universidade Federal Do Rio Grande Do Sul - UFRGS, Porto Alegre, RS, Brazil

    Guido Lenz

Authors
  1. Isabele Cristiana Iser
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  2. Liziane Raquel Beckenkamp
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  3. Juliana Hofstatter Azambuja
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  12. Márcia Rosângela Wink
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Contributions

ICI performed cell culture, in vivo experiments, and wrote the manuscript. LRB and JHA assisted with in vivo glioma model. APSB performed RT-qPCR assays. EB contributed with the glioma model and with the interpretation of the results; FLR assisted with animal perfusions; MCF assisted with histological analysis and the interpretation of data; RCSA analyzed the pathology of gliomas; LLX contributed with GFAP immunohistochemistry quantification; PAB assisted with the statistics and interpretation of the results; MRW got and coordinate the grants, supervised the experiments, assisted in drafting and critical reading. GL supervised the experiments and assisted with critical reading. All the authors discussed the results and contributed to the writing of the manuscript.

Corresponding author

Correspondence to Márcia Rosângela Wink.

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Conflict of interest

The authors have no conflict of interest to declare.

Ethics Approval

The protocols used in this study were approved by the Ethics Committee on Animal Use (CEUA) of Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), under the number 104/11, following the resolutions of the CONCEA (Conselho Nacional de Controle de Experimentação Animal). The NIH ‘‘Guide for the Care and Use of Laboratory Animals’’ (NIH publication nº 80–23, revised 1996) was followed in all experiments. The surgeries were performed with all efforts to minimize the animals suffering.

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The authors are alone responsible for the content and writing of the paper. All authors reviewed and approved the final version of the manuscript.

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Iser, I.C., Beckenkamp, L.R., Azambuja, J.H. et al. Rat Adipose-Derived Stromal Cells (ADSCs) Increases the Glioblastoma Growth and Decreases the Animal Survival. Stem Cell Rev and Rep 18, 1495–1509 (2022). https://doi.org/10.1007/s12015-021-10227-6

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