Abstract

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.

Highlights

  • In the present study, a protocol was developed for processing of human adipose derived mesenchymal stem cell secretome formulation of varying concentration

  • The results reported by Schneider et al.[37] and Kanehiraet al.[38], showed that the conditioned media derived from mesenchymal stem cells isolated from a healthy physiological source have the ability to inhibit cancer cell growth

  • We develop a protocol for the use of human adipose derived mesenchymal stem cell (MSC) secretome to create a formulation with well-defined secretome concentration, evaluate its molecular composition, and explore its effectiveness, in vitro and in vivo, in suppressing breast cancer in a dose dependent manner

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Summary

Introduction

A protocol was developed for processing of human adipose derived mesenchymal stem cell secretome formulation of varying concentration. We use in vitro and in vivo models of triple negative breast ­cancer[3] (TNBC) lacking estrogen, progesterone and human epidermal growth factor 2 (HER2) receptors which is an aggressive form of breast cancer showing c­ hemo[4,5] and immune resistant phenotype with poor response to targeted ­therapies[6,7] to evaluate the anti-cancer potential. The stem cell conditioned media has shown the opposite effect in some cases, namely promotion of ­cancer[46,47,48,49,50]. Development of a stem cell secretome formulation which can reproducibly demonstrate the suppression of cancer is essential

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