Mesenchymal stem cell exosomes: a two-edged sword in cancer therapy

Faezeh Vakhshiteh,1 Fatemeh Atyabi,1,2 Seyed Nasser Ostad3 1Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 2Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Abstract: Mesenchymal stem cells (MSCs) are multipotent stromal cells present in various adult tissues. Several studies suggest that MSCs secrete exosomes that perform as mediators in the tumor niche and play several roles in tumorigenesis, angiogenesis, and metastasis. In contrast, there are other studies supporting the tumor-suppressing effects of MSC-derived exosomes. Therefore, the exact association of MSC exosomes and tumor cells remains open to debate. This review aimed to demonstrate the present knowledge of MSC-derived exosomes in cancer research and to illustrate current approaches to make use of modified exosomes as a platform in therapeutic strategies in cancer. Keywords: mesenchymal stem cells, exosome, drug delivery, exosome engineering, cancer therap

Peptide-conjugated liposomes for targeted miR-34a delivery to suppress breast cancer and cancer stem-like population

MicroRNAs perform critical roles in regulation of cancer cells and cancer stem cells (CSCs). CSCs are key contributors of therapy failure; hence, successful tumor therapy requires elimination of both CSCs and tumor cells. MicroRNA-34a (miR-34a) is a well-defined tumor suppressor microRNA which is hypermethylated in breast cancer. Cyclic RGD (cRGD) is a targeting peptide that selectively target integrin receptor-expressing cells. Herein, cRGD-conjugated Polyethylene glycol-modified (PEGylated) liposomes (cRGD-PEG liposomes) encapsulating miR-34a (cRGD-PEG/miR-34a liposomes) was developed for targeted transport of miR-34a into MDA-MB-231 breast cancer cells. A 1.8-fold higher internalization of cRGD-targeted liposomes effectively increased the accumulation of miR-34a in breast carcinoma cells. Notably, cRGD-targeted miR-34a-loaded liposomes showed significant inhibitory outcome on tumor cell growth, migration, and invasion as well as a significant decrease in the percentage of CD44+/CD24�/low cancer stem-like population. The results suggest that cRGD-targeted liposomes may possibly increase the efficiency of therapeutic MicroRNAs in breast carcinoma cells and CSCs. © 2020 Elsevier B.V

Exosomes derived from miR-34a-overexpressing mesenchymal stem cells inhibit in vitro tumor growth: A new approach for drug delivery

Aims: Exosomes hold great promise as bio-inspired delivery vehicles. Mesenchymal stem cells (MSCs) are recognized for their potential to yield huge quantities of exosomes. We aimed to investigate the potential use of modified exosomes derived from genetically modified dental pulp MSCs (DPSCs) as a carrier to deliver tumor suppressor miR-34a to repress proliferation of breast carcinoma cells. Materials and methods: miR-34a-overexpressing DPSCs were prepared using XMIRXpress-34a lentivectors. The anticancer effects of the miR-34a-loaded exosomes were evaluated on breast carcinoma cells through apoptosis, migration, and invasion assays. Given the structural similarity between exosomes and liposomes, we compared the exosome-mediated miRNA delivery efficiency with that of liposomes. Key findings: Our data demonstrated that genetically modified DPSCs were capable of secretion of exosomes enriched with therapeutic miRNAs and presented the feasibility of application of exosome-based vehicle for gene delivery. Significance: We showed the potential of MSC-derived exosomes as a tool for delivery of miRNAs in vitro. Nevertheless, optimizing gene-loading approaches is required before exosomes can be intended as a miRNA carrier for therapeutic applications. © 202

The burden of prostate cancer in North Africa and Middle East, 1990–2019: Findings from the global burden of disease study

Background: Prostate cancer (PCa) is the second most prevalent cancer among men worldwide. This study presents estimates of PCa prevalence, incidence, death, years-of-life-lost (YLLs), years-lived-with-disability (YLDs), disability-adjusted-life-years (DALYs), and the burden attributable to smoking during 1990-2019 in North Africa and Middle East using data of Global Burden of Diseases (GBD) Study 2019. Methods: This study is a part of GBD 2019. Using vital registration and cancer registry data, the estimates on PCa burden were modeled. Risk factor analysis was performed through the six-step conceptual framework of Comparative Risk Assessment. Results: The age-standardized rates (95 UI) of PCa incidence, prevalence, and death in 2019 were 23.7 (18.5-27.9), 161.1 (126.6-187.6), and 11.7 (9.4-13.9) per 100,000 population. While PCa incidence and prevalence increased by 77 and 144 during 1990-2019, respectively, the death rate stagnated. Of the 397 increase in PCa new cases, 234 was due to a rise in the age-specific incidence rate, 79 due to population growth, and 84 due to population aging. The YLLs, YLDs, and DALYs of PCa increased by 2 (-11.8-23.1), 108 (75.5-155.1), and 6 (-8.9-28.1). The death rate and DALYs rate attributable to smoking have decreased 12 and 10, respectively. The DALYs rate attributable to smoking was 37.4 (15.9-67.8) in Lebanon and 5.9 (2.5-10.6) in Saudi Arabia, which were the highest and lowest in the region, respectively. Conclusions: The PCa incidence and prevalence rates increased during 1990-2019; however, the death rate stagnated. The increase in the incidence was mostly due to the rise in the age-specific incidence rate, rather than population growth or aging. The burden of PCa attributable to smoking has decreased in the past 30 years. Copyright © 2022 Abbasi-Kangevari, Saeedi Moghaddam, Ghamari, Azangou-Khyavy, Malekpour, Rezaei, Rezaei, Kolahi, GBD 2019 NAME Prostate Cancer Collaborators, Amini, Mokdad, Jamshidi, Naghavi, Larijani and Farzadfar