The targeted inhibitory effects of human amniotic fluid stem cells carrying CXCR4 promoter and DAL-1 on non-small cell lung carcinoma growth

Abstract

The differentially expressed in adenocarcinoma of the lung-1 (DAL-1) protein has been demonstrated to be suppressive to various types of tumors including lung cancer. This study aimed to determine the targeted effects of human amniotic fluid stem cells (hAFS cells) carrying CXCR4 promoter driven conditionally replicable adenovirus vector overexpressing DAL-1 (Ad-CXCR4-DAL-1) on non-small cell lung carcinoma (NSCLC) growth. The apoptotic effects of virus vectors were assessed using flow cytometry, and the cytotoxicity analyzed by CCK-8 assay. In vivo imaging system was used to determine the homing capability of hAFS cells. A549 cell xenograft mouse model was created to assess the in vivo effect of DAL-1 overexpression on NSCLC growth. We found that infection of Ad-CXCR4-DAL-1 increased the apoptosis of A549 NSCLC cells but not 16HBE normal human bronchial epithelial cells. Ad-CXCR4-DAL-1 administered via intratumoral injection led to significant reduced growth and greater necrosis of A549 xenograft tumors comparing to null vector treated animals. When infused via tail vein, hAFS cells carrying Ad-CXCR4-DAL-1 homed to lung cancer xenografts, caused virus replication and DAL-1 overexpression, and led to significant lower growth and greater necrosis of A549 cell xenografts comparing to non-treatment control. In conclusion, hAFS cells are capable of carrying Ad-CXCR4-DAL-1 vectors, specifically targeting to lung cancer, and causing oncolytic effects when administered in vivo.

Stem Cells Derived from Amniotic Fluid: A Potential Pluripotent-Like Cell Source for Cellular Therapy?

“…The latter is especially important, because AFSCs represent a well-suited alternative stem cell source, obviating the need for iPSC generation to discover the molecular biological changes associated with genetic disorders [99,100]. Besides that, the imperative need is to translate AFSCs from bench to clinic stems from the demonstration of their anti-cancer activity in vitro [101][102][103]. Further exploration of their anti-cancer effect in preclinical animal models would pave the road to ultimately utilize them in cancer treatment, which may possibly and plausibly replace the need for chemotherapy in the future that is often associated with the undesirable side effects, causing drug resistance and toxicities to normal cells [104].…”

An update clinical application of amniotic fluid-derived stem cells (AFSCs) in cancer cell therapy and tissue engineering

“…Because hAFSCs are not tumorigenic in vivo, so these can be used in eventual clinical applications for regenerative medicine because injections of hAF-MSCs into immunodeficient animals do not induce tumor formation (Sessarego et al 2008). Using of AFSCs are free of ethical constraints, and without injury to the fetus, they can be readily isolated during amniocentesis, thus shown great promising in treatment of diseases including cancer (Bitsika et al 2011, Li et al 2015, and other diseases such as kidney (Hauser et al 2010, Perin et al 2010, Neural disorders (Rosser et al 2007), cardiac disease (Bollini et al 2011a(Bollini et al , 2011b, intestinal disorders (Zani et al 2013), lung diseases (Joo et al 2012, Li et al 2016, or dermal and embryo disorders (Shaw et al 2011, Skardal et al 2012 and some applications of human amniotic membrane-derived mesenchymal stem cell (Jiao et al 2012, Zhang et al 2011 and human amniotic membrane-derived epithelial stem cell (Luo et al 2011, Manuelpillai et al 2010, Marongiu et al 2011 were shown in Table 2.…”

“…Type of stem cells Human amniotic fluid-derived stem cell Ovarian cancer (Li et al 2015) Bladder cancer (Bitsika et al 2011) Acute kidney injury (Hauser et al 2010) Acute tubular necrosis (Perin et al 2010) Transplantation for neurodegenerative diseases (Rosser et al 2007) Myocardial infarction (Bollini et al 2011a) Cardiomyogenic differentiation (Bollini et al 2011b) Repair of damaged intestine (Zani et al 2013) Integrate into murine lung and differentiate into lung specify (Joo et al 2012) lung cancer, carrying CXCR4 promoter and DAL-1 on nonsmall-cell lung carcinoma growth (Li et al 2016) Wound healing (Skardal et al 2012) Prenatal and postnatal therapy (Shaw et al 2011) Human amniotic membrane-derived mesenchymal stem cell…”

SIRT3 Facilitates Amniotic Fluid Stem Cells to Repair Diabetic Nephropathy Through Protecting Mitochondrial Homeostasis by Modulation of Mitophagy

“…However, adult bone marrow stem cells are difficult to obtain and have a more restricted differentiation potential and a shorter life span than amniotic fluid stem cells (AFSCs), which is disadvantageous. Previous studies have demonstrated that AFSCs engraftment repairs lung injury [9], reduces cerebral ischemia damage [10], inhibits non-small cell lung carcinoma growth [11], alleviates acute kidney damage [12], protects β-cells against high glucose-induced stress [13], attenuates oxidative stress after kidney engraftment [14], and slows the development of heart failure [15]. For DN, although both animal and clinical studies have provided information that suggests stem cell transplantation improves renal function through possible glomerular formation and/or angiogenesis, few studies have investigated the effects of AFSC treatment on DN progression.…”