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Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer

In the present study, a protocol was developed for processing of human adipose derived mesenchymal stem cell secretome formulation of varying concentration. Its molecular composition was evaluated, and its effectiveness in vitro using breast cancer cell lines, and in vivo in a nude mice breast cance...

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Autores principales: Nadesh, Ragima, Menon, Krishnakumar N., Biswas, Lalitha, Mony, Ullas, Subramania Iyer, K., Vijayaraghavan, Sundeep, Nambiar, Ajit, Nair, Shantikumar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648896/
https://www.ncbi.nlm.nih.gov/pubmed/34873206
http://dx.doi.org/10.1038/s41598-021-01878-z
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author Nadesh, Ragima
Menon, Krishnakumar N.
Biswas, Lalitha
Mony, Ullas
Subramania Iyer, K.
Vijayaraghavan, Sundeep
Nambiar, Ajit
Nair, Shantikumar
author_facet Nadesh, Ragima
Menon, Krishnakumar N.
Biswas, Lalitha
Mony, Ullas
Subramania Iyer, K.
Vijayaraghavan, Sundeep
Nambiar, Ajit
Nair, Shantikumar
author_sort Nadesh, Ragima
collection PubMed
description In the present study, a protocol was developed for processing of human adipose derived mesenchymal stem cell secretome formulation of varying concentration. Its molecular composition was evaluated, and its effectiveness in vitro using breast cancer cell lines, and in vivo in a nude mice breast cancer model was studied to determine its role in suppressing triple negative breast cancer in a dose dependent manner. Because the secretome could have value as an add-on therapy along with a current drug, the effectiveness of the secretome both in monotherapy and in combination therapy along with paclitaxel was evaluated. The results showed significant cell kill when exposed to the secretome above 20 mg/ml at which concentration there was no toxicity to normal cells. 70 mg/ml of SF showed 90 ± 10% apoptosis and significant decrease in CD44(+)/CD24(−), MDR1+ and PDL-1+ cancer cells. In vivo, the tumor showed no growth after daily intra tumor injections at 50 mg/ml and 100 mg/ml doses whereas substantial tumor growth occurred after saline intra tumor injection. The study concludes that SF is a potential biotherapeutic for breast cancer and could be used initially as an add-on therapy to other standard of care to provide improved efficacy without other adverse effects.
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spelling pubmed-86488962021-12-08 Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer Nadesh, Ragima Menon, Krishnakumar N. Biswas, Lalitha Mony, Ullas Subramania Iyer, K. Vijayaraghavan, Sundeep Nambiar, Ajit Nair, Shantikumar Sci Rep Article In the present study, a protocol was developed for processing of human adipose derived mesenchymal stem cell secretome formulation of varying concentration. Its molecular composition was evaluated, and its effectiveness in vitro using breast cancer cell lines, and in vivo in a nude mice breast cancer model was studied to determine its role in suppressing triple negative breast cancer in a dose dependent manner. Because the secretome could have value as an add-on therapy along with a current drug, the effectiveness of the secretome both in monotherapy and in combination therapy along with paclitaxel was evaluated. The results showed significant cell kill when exposed to the secretome above 20 mg/ml at which concentration there was no toxicity to normal cells. 70 mg/ml of SF showed 90 ± 10% apoptosis and significant decrease in CD44(+)/CD24(−), MDR1+ and PDL-1+ cancer cells. In vivo, the tumor showed no growth after daily intra tumor injections at 50 mg/ml and 100 mg/ml doses whereas substantial tumor growth occurred after saline intra tumor injection. The study concludes that SF is a potential biotherapeutic for breast cancer and could be used initially as an add-on therapy to other standard of care to provide improved efficacy without other adverse effects. Nature Publishing Group UK 2021-12-06 /pmc/articles/PMC8648896/ /pubmed/34873206 http://dx.doi.org/10.1038/s41598-021-01878-z Text en © The Author(s) 2021, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Nadesh, Ragima
Menon, Krishnakumar N.
Biswas, Lalitha
Mony, Ullas
Subramania Iyer, K.
Vijayaraghavan, Sundeep
Nambiar, Ajit
Nair, Shantikumar
Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer
title Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer
title_full Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer
title_fullStr Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer
title_full_unstemmed Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer
title_short Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer
title_sort adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648896/
https://www.ncbi.nlm.nih.gov/pubmed/34873206
http://dx.doi.org/10.1038/s41598-021-01878-z
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