Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, 682041, India.
Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, Kerala, 682041, India.
Sci Rep. 2021 Dec 6;11(1):23435. doi: 10.1038/s41598-021-01878-z.
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.
在本研究中，开发了一种方案来处理不同浓度的人脂肪来源间充质干细胞分泌因子制剂。评估了其分子组成，并在体外使用乳腺癌细胞系和体内裸鼠乳腺癌模型研究了其有效性，以确定其在以剂量依赖方式抑制三阴性乳腺癌方面的作用。由于分泌因子可能作为附加疗法与现有药物一起具有价值，因此评估了分泌因子在单独治疗和联合紫杉醇治疗中的有效性。结果表明，当暴露于 20mg/ml 以上的分泌因子时，细胞杀伤作用显著，在该浓度下对正常细胞没有毒性。70mg/ml 的 SF 表现出 90±10%的凋亡和 CD44/CD24、MDR1+和 PDL-1+癌细胞的显著减少。在体内，每天在肿瘤内注射 50mg/ml 和 100mg/ml 剂量后肿瘤没有生长，而在肿瘤内注射生理盐水后则发生了大量肿瘤生长。该研究得出结论，SF 是一种有潜力的乳腺癌生物治疗药物，最初可作为其他标准治疗的附加疗法，以在不产生其他不良反应的情况下提供更好的疗效。
