The role of the mesenchymal stromal cell- (MSC-) derived secretome is becoming increasingly intriguing from a clinical perspective due to its ability to stimulate endogenous tissue repair processes as well as its effective regulation of the immune system, mimicking the therapeutic effects produced by the MSCs. The secretome is a composite product secreted by MSC in vitro (in conditioned medium) and in vivo (in the extracellular milieu), consisting of a protein soluble fraction (mostly growth factors and cytokines) and a vesicular component, extracellular vesicles (EVs), which transfer proteins, lipids, and genetic material. MSC-derived secretome differs based on the tissue from which the MSCs are isolated and under specific conditions (e.g., preconditioning or priming) suggesting that clinical applications should be tailored by choosing the tissue of origin and a priming regimen to specifically correct a given pathology. MSC-derived secretome mediates beneficial angiogenic effects in a variety of tissue injury-related diseases. This supports the current effort to develop cell-free therapeutic products that bring both clinical benefits (reduced immunogenicity, persistence in vivo, and no genotoxicity associated with long-term cell cultures) and manufacturing advantages (reduced costs, availability of large quantities of off-the-shelf products, and lower regulatory burden). In the present review, we aim to give a comprehensive picture of the numerous components of the secretome produced by MSCs derived from the most common tissue sources for clinical use (e.g., AT, BM, and CB). We focus on the factors involved in the complex regulation of angiogenic processes.

Mesenchymal stromal cells (MSCs), formerly known as mesenchymal stem cells, are nonhematopoietic multipotent cells and are emerging worldwide as the most clinically used and promising source for allogeneic cell therapy. MSCs, initially obtained from bone marrow, can be derived from several other tissues, such as adipose tissue, placenta, and umbilical cord. Diversity in tissue sourcing and manufacturing procedures has significant effects on MSC products. However, in 2006, a minimal set of standard criteria has been issued by the International Society of Cellular Therapy for defining derived MSCs. These include adherence to plastic in conventional culture conditions, particular phenotype, and multilineage differentiation capacity in vitro. Moreover, MSCs have trophic capabilities, a high in vitro self-renewal ability, and immunomodulatory characteristics. Thus, immunosuppressive treatment with MSCs has been proposed as a potential therapeutic alternative for conditions in which the immune system cells influence outcomes, such as inflammatory and autoimmune diseases. The precise mechanism by which MSCs affect functions of most immune effector cells is not completely understood but involves direct contact with immune cells, soluble mediators, and local microenvironmental factors. Recently, it has been shown that their homeostatic resting state requires activation, which can be achieved in vitro with various cytokines, including interferon-γ. In the present review, we focus on the suppressive effect that MSCs exert on the immune system and highlight the significance of in vitro preconditioning and its use in preclinical studies. We discuss the clinical aspects of using MSCs as an immunomodulatory treatment. Finally, we comment on the risk of interfering with the immune system in regard to cancer formation and development.

When malignant melanoma is diagnosed early, surgical resection is the intervention of choice and is often curative, but many patients present with unresectable disease at later stages. Due to its complex etiology paired with well-documented chemoresistance and high metastatic potential, patients with advanced melanoma had a poor prognosis, and the treatment of this disease remained unsatisfactory for many years. Recently, targeted therapy, immune checkpoint inhibition, or combinatory approaches have revolutionized the therapeutic options of melanoma allowing considerable improvement in disease control and survival. In this review we will summarize these novel therapeutic strategies with particular focus on combinatory immunotherapies and further discuss recent data derived from immunogenomic studies and potential options to improve the therapeutic efficacy of immune modulatory approaches.

The gene expression analysis of formalin-fixed paraffin-embedded (FFPE) tissues is often hampered by poor RNA quality, which results from the oxidation, cross-linking and other chemical modifications induced by the inclusion in paraffin. Yet, FFPE samples are a valuable source for molecular studies and can provide great insights into disease progression and prognosis. With the advancement of genomic technologies, new methods have been established that offer reliable and accurate gene expression workflows on samples of poor quality. NanoString is a probe-based technology that allows the direct counting of the mRNA transcripts and can be applied to degraded samples. Here, we have tested 2 RNA extraction methods for FFPE samples, and we have performed a titration experiment to evaluate the impact of RNA degradation and RNA input on the gene expression profiles assessed using the NanoString IO360 panel. We have selected FFPE samples of different DV200 values and assessed them on the nCounter platform with 2 different amounts of input RNA. This study concludes that the nCounter is a robust and reliable platform to assess the gene expression of RNA samples with DV200 > 30%; its robustness and ease of use could be of particular benefit to clinical settings.

New technologies and therapies designed to facilitate development of personalized treatments are rapidly emerging in the field of biomedicine. Strikingly, the goal of personalized medicine refined the concept of therapy by developing cell-based therapies, the so-called “living drugs”. Breakthrough advancements were achieved in this regard in the fields of gene therapy, cell therapy, tissue-engineered products and advanced therapeutic techniques. The Advanced Therapies in Healthcare symposium, organized by the Clinical Research Center Department of Sidra Medicine, in Doha, Qatar (October 2017), brought together world-renowned experts from the fields of oncology, hematology, immunology, inflammation, autoimmune disorders, and stem cells to offer a comprehensive picture of the status of worldwide advanced therapies in both pre-clinical and clinical development, providing insights to the research phase, clinical data and regulatory aspects of these therapies. Highlights of the meeting are provided in this meeting report.