Therapeutic Potential of Secreted Molecules Derived from Human Amniotic Fluid Mesenchymal Stem/Stroma Cells in a Mice Model of Colitis

Abstract

Inflammatory bowel diseases (IBDs) are the result of pathological immune responses due to environmental factors or microbial antigens into a genetically predisposed individual. Mainly due to their trophic properties, a mounting interest is focused on the use of human mesenchymal stem/stromal cells (hMSCs) to treat IBD disease in animal models. The aim of the study is to test whether the secreted molecules, derived from a specific population of second trimester amniotic fluid mesenchymal stem/stromal cells, the spindle-shaped MSCs (SS-AF-MSCs), could be utilized as a novel therapeutic, cell free approach for IBD therapy. Induction of colitis was achieved by oral administration of dextran sulphate sodium (DSS) (3 % w/v in tap water), for 5 days, to 8-week-old NOD/SCID mice. The progression of colitis was assessed on a daily basis through recording the body weight, stool consistency and bleeding. Conditioned media (CM) derived from SS-AF-MSCs were collected, concentrated and then delivered intraperitoneally into DSS treated mice. To evaluate and determine the inflammatory cytokine levels, histopathological approach was applied. Administration of CM derived from SS-AF-MSCs cells reduced the severity of colitis in mice. More importantly, TGFb1 protein levels were increased in the mice received CM, while TNFa and MMP2 protein levels were decreased, respectively. Accordingly, IL-10 was significantly increased in mice received CM, whereas TNFa and IL-1b were decreased at mRNA level. Our results demonstrated that CM derived from SS-AF-MSCs cells is able to ameliorate DSS-induced colitis in immunodeficient colitis mouse model, and thus, it has a potential for use in IBD therapy.

The Achievements and Challenges of Mesenchymal Stem Cell-Based Therapy in Inflammatory Bowel Disease and Its Associated Colorectal Cancer

“…The higher convenience of obtaining adipose and umbilical cord MSCs has also increased their application across several studies [3,62]. Other sources of MSCs applied in IBD and colitis-associated CRC are amniotic fluid [63], placenta [64], tonsil [65], amnion [66,67], and endometrium regenerative cells [68], among others. The routes of administration are intraperitoneal, intravenous, and anal injection.…”

Biological activity of mesenchymal stem cells secretome as a basis for cell-free therapeutic approach

“…Yi and Song (2012) described that MSCs inhibited proinflammatory cytokines, such as interferon (IFN)-γ and tumour necrosis factor α (TNFα), while increasing release of anti-inflammatory IL10. Legaki et al (2016) showed that hUCESC-CM treatment significantly reduced mRNA expression of pro-inflammatory cytokines (IL6, IL8, TNFα and macrophage inflammatory protein-1 alpha (MIP-1α)), but increased mRNA expression of the anti-inflammatory cytokine (IL10). The similar results were obtained during experiments with MSC-CM from amniotic fluid in a mice colitis model (Legaki et al 2016).…”

“…Legaki et al (2016) showed that hUCESC-CM treatment significantly reduced mRNA expression of pro-inflammatory cytokines (IL6, IL8, TNFα and macrophage inflammatory protein-1 alpha (MIP-1α)), but increased mRNA expression of the anti-inflammatory cytokine (IL10). The similar results were obtained during experiments with MSC-CM from amniotic fluid in a mice colitis model (Legaki et al 2016). It was also found that hUCESC-CM reduced the infiltration of leucocytes in ocular tissues (Vishnubhatla et al 2014).…”

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

“…Interestingly, it has been recently reported that AFSC secretome contains key molecules that mediate tissue repair and regeneration in muscle damage, possibly through their observed ability to stimulate stem cell proliferation and migration, induce angiogenesis, as well as their antiinflammatory and anti-senescence effect [84]. Besides this, in an experimental model of colitis, secreted molecules (in conditioned media) from AFSCs have been demonstrated to ameliorate the condition through reducing inflammatory response, as evidenced through the increased expression of IL-10, as well as the decrease in TNF and IL-1 expression [85]. Similarly, AFSCs have been reported to promote neovascularization through releasing a set of angiogenic factors such as MMP-9, MCP-1, endothelin-1, angiogenin and TIMP-1 [86].…”