The Immunological Profile of Adipose Mesenchymal Stromal/Stem Cells after Cell Expansion and Inflammatory Priming.

BACKGROUND: AT-MSCs display great immunoregulatory features, making them potential candidates for cell-based therapy. This study aimed to evaluate the "RBC lysis buffer" isolation protocol and immunological profiling of the so-obtained AT-MSCs. METHODS: We established an immune-comparative screening of AT-MSCs throughout in vitro cell expansion (PM, P1, P2, P3, P4) and inflammatory priming regarding the expression of 28 cell-surface markers, 6 cytokines/chemokines, and 10 TLR patterns. FINDINGS: AT-MSCs were highly expandable and sensitive to microenvironment challenges, hereby showing plasticity in distinct expression profiles. Both cell expansion and inflammation differentially modulated the expression profile of CD34, HLA-DR, CD40, CD62L, CD200 and CD155, CD252, CD54, CD58, CD106, CD274 and CD112. Inflammation resulted in a significant increase in the expression of the cytokines IL-6, IL-8, IL-1ß, IL-1Ra, CCL5, and TNFα. Depending on the culture conditions, the expression of the TLR pattern was distinctively altered with TLR1-4, TLR7, and TLR10 being increased, whereas TLR6 was downregulated. Protein network and functional enrichment analysis showed that several trophic and immune responses are likely linked to these immunological changes. CONCLUSIONS: AT-MSCs may sense and actively respond to tissue challenges by modulating distinct and specific pathways to create an appropriate immuno-reparative environment. These mechanisms need to be further characterized to identify and assess a molecular target that can enhance or impede the therapeutic ability of AT-MSCs, which therefore will help improve the quality, safety, and efficacy of the therapeutic strategy.

The immunogenic profile and immunomodulatory function of mesenchymal stromal / stem cells in the presence of Ptychotis verticillata.

Mesenchymal stromal/stem cells (MSCs) are considered to be a promising immunotherapeutic tool due to their easy accessibility, culture expansion possibilities, safety profile, and immunomodulatory properties. Although several studies have demonstrated the therapeutic effects of MSCs, their efficacy needs to be improved while also preserving their safety. It has been suggested that cell homeostasis may be particularly sensitive to plant extracts. The impact of natural compounds on immunity is thus a fascinating and growing field. Ptychotis verticillata and its bioactive molecules, carvacrol and thymol, are potential candidates for improving MSC therapeutic effects. They can be used as immunotherapeutic agents to regulate MSC functions and behavior during immunomodulation. Depending on their concentrations and incubation time, these compounds strengthened the immunomodulatory functions of MSCs while maintaining their immune-evasive profile. Incubating MSCs with carvacrol and thymol does not alter their hypoimmunogenicity, as no induction of the allogeneic immune response was observed. MSCs also showed enhanced abilities to reduce the proliferation of activated T cells. Thus, MSCs are immunologically responsive to bioactive molecules derived from PV. The bioactivity may depend on the whole phyto-complex of the oil. These findings may contribute to the development of safe and efficient immunotherapeutic MSCs by using medicinal plant-derived active molecules.

Umbilical Cord Mesenchymal Stromal/Stem Cells and Their Interplay with Th-17 Cell Response Pathway.

As a form of immunomodulatory therapeutics, mesenchymal stromal/stem cells (MSCs) from umbilical cord (UC) tissue were assessed for their dynamic interplay with the Th-17 immune response pathway. UC-MSCs were able to modulate lymphocyte response by promoting a Th-17-like profile. Such modulation depended on the cell ratio of the cocultures as well as the presence of an inflammatory setting underlying their plasticity. UC-MSCs significantly increased the expression of IL-17A and RORγt but differentially modulated T cell expression of IL-23R. In parallel, the secretion profile of the fifteen factors (IL1ß, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22, IL-21, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α) involved in the Th-17 immune response pathway was substantially altered during these cocultures. The modulation of these factors demonstrates the capacity of UC-MSCs to sense and actively respond to tissue challenges. Protein network and functional enrichment analysis indicated that several biological processes, molecular functions, and cellular components linked to distinct Th-17 signaling interactions are involved in several trophic, inflammatory, and immune network responses. These immunological changes and interactions with the Th-17 pathway are likely critical to tissue healing and may help to identify molecular targets that will improve therapeutic strategies involving UC-MSCs.

Fundamental and Applied Advances in Stem Cell Therapeutic Research.

We are pleased to present this Special Issue of Cells, entitled 'Feature Papers in Stem Cells' [...].

Bioscreening and pre-clinical evaluation of the impact of bioactive molecules from Ptychotis verticillata on the multilineage potential of mesenchymal stromal cells towards immune- and inflammation-mediated diseases.

OBJECTIVE AND DESIGN: Mesenchymal stromal cells (MSCs) are currently used in cell reparative medicine due to their trophic and ant-inflammatory properties. The modulation of stem cell properties by phytochemicals has been suggested as a tool to empower their tissue repair capacity. In vitro, MSCs are characterized by their tri-lineage potential that holds great interest for tissue regeneration. Ptychotis Verticillata (PV), an aromatic and medicinal plant, may be thus used to modulate the in vitro multilineage potential of MSCs. MATERIALS AND METHODS: We screened the impact of PV-derived essential oil and their bioactive molecules (thymol and carvacrol) on the in vitro multilineage potential of MSCs. Different concentrations and incubation times of these compounds were assessed during the osteogenesis and adipogenesis of MSCs. RESULTS: The analysis of 75 conditions indicates that these compounds are biologically active by promoting two major differentiation lineages from MSCs. In a time- and dose-dependent manner, thymol and carvacrol increased the osteogenesis and adipogenesis. CONCLUSION: According to these preliminary observations, the addition of PV extract may stimulate the tissue regenerative and repair functions of MSCs. Further optimization of compound extraction and characterization from PV as well as cell treatment conditions should increase their therapeutic value in combination with MSCs.