Earlier research primarily attributed the effects of mesenchymal stem cell (MSC) therapies to their capacity for local engrafting and differentiating into multiple tissue types. However, recent studies have revealed that implanted cells do not survive for long, and that the benefits of MSC therapy could be due to the vast array of bioactive factors they produce, which play an important role in the regulation of key biologic processes. Secretome derivatives, such as conditioned media or exosomes, may present considerable advantages over cells for manufacturing, storage, handling, product shelf life and their potential as a ready-to-go biologic product. Nevertheless, regulatory requirements for manufacturing and quality control will be necessary to establish the safety and efficacy profile of these products. Among MSCs, human uterine cervical stem cells (hUCESCs) may be a good candidate for obtaining secretome-derived products. hUCESCs are obtained by Pap cervical smear, which is a less invasive and painful method than those used for obtaining other MSCs (for example, from bone marrow or adipose tissue). Moreover, due to easy isolation and a high proliferative rate, it is possible to obtain large amounts of hUCESCs or secretome-derived products for research and clinical use.

It has been reported that stromal cell features may affect the clinical outcome of breast cancer patients. Cancer associated fibroblasts (CAFs) represent one of the most abundant cell types within the breast cancer stroma. Here, we aimed to explore the influence of CAFs on breast cancer gene expression, as well as on invasion and angiogenesis.

It is well known that nitric oxide (NO) plays an important role in the pathogenesis of inflammatory diseases. Eucalyptus globulus Labill. and Thymus vulgaris L. have been used in traditional medicine in the treatment of bronchitis, asthma and other respiratory diseases. The present study focuses on the effects of these two extracts on NO production induced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) in the murine macrophage cell line J774A.1. In addition, cell viability, scavenging activity and inducible nitric oxide synthase (iNOS) mRNA expression were evaluated. E. globulus and T. vulgaris extracts significantly inhibited the enhanced production of NO induced by LPS and IFN-γ in a dose-dependent manner. Treatment with these two extracts did not reduce cell viability at any dose used. Both plant extracts showed significant scavenging of NO radicals released by an NO donor, PAPANONOate. Results also show that pre-treatment with E. globulus and T. vulgaris extracts significantly inhibits iNOS mRNA expression. This study thus suggests that the inhibition of net NO production by these two extracts may be due to their NO scavenging activity and/or their inhibitory effects on iNOS gene expression.

Mesenchymal stem cells (MSCs) are present in all organs and tissues, playing a well-known function in tissue regeneration. However, there is also evidence indicating a broader role of MSCs in tissue homeostasis. In vivo studies have shown MSC paracrine mechanisms displaying proliferative, immunoregulatory, anti-oxidative, or angiogenic activity. In addition, recent studies also demonstrate that depletion and/or dysfunction of MSCs are associated with several systemic diseases, such as lupus, diabetes, psoriasis, and rheumatoid arthritis, as well as with aging and frailty syndrome. In this review, we hypothesize about the role of MSCs as keepers of tissue homeostasis as well as modulators in a variety of inflammatory and degenerative systemic diseases. This scenario opens the possibility for the use of secretome-derived products from MSCs as new therapeutic agents in order to restore tissue homeostasis, instead of the classical paradigm “one disease, one drug”.

PURPOSE. To evaluate the effect of Conditioned Medium from human uterine cervical stem cells (CM-hUCESCs) on corneal epithelial healing in a rat model of dry eye after alkaline corneal epithelial ulcer. We also tested the bactericide effect of CM-hUCESCs. METHODS. Dry eye was induced in rats by extraocular lacrimal glands excision, and corneal ulcers were produced using NaOH. Corneal histological evaluation was made with hematoxylin-eosin (H&E) staining. Real-time PCR was used to evaluate mRNA expression levels of pro-inflammatory cytokines. We also studied the bactericide effect of CM-hUCESCs in vitro and on infected corneal contact lenses (CLs) using Escherichia coli (E. coli) and Staphylococcus epidermidis (S. epidermidis) bacteria. In addition, in order to investigate proteins from CM-hUCESCs that could mediate these effects, we carried out a human cytokine antibody array. RESULTS. After injury, dry eyes treated with CM-hUCESCs significantly improved epithelial regeneration, and showed reduced corneal MIP-1α and TNF-α mRNA expression, as compared to untreated eyes and eyes treated with culture medium or sodium hyaluronate ophthalmic drops. In addition, we found in CM-hUCESCs high levels of proteins, such as tissue inhibitors of metalloproteinases -1 and -2, fibroblast growth factor -6 and -7, urokinase receptor, and hepatocyte growth factor, that could mediate these effects. In vitro, CM-hUCESCs showed a clear bactericide effect on both E. coli and S. epidermidis, and CLs infected with S. epidermidis. Analyses of CM-hUCESCs showed elevated levels of proteins that could be involved in the bactericide effect, such as the chemokine (C-X-C motif) ligands -1, -6, -8, -10, and the chemokine (C-C motif) ligands -5, and -20. CONCLUSIONS. Treatment with CM-hUCESCs improved wound healing of alkali-injured corneas and showed a strong bactericide effect on CLs. Patients using CLs and suffering dry eye, allergies induced by commercial solutions, or small corneal injuries could benefit from this treatment.