Background: The infiltration of the stromal vascular fraction (SVF) of autologous adipose tissue to treat osteoarthritis has been used for several years demonstrating its safety and noticeable efficacy. This article presents clinical data from patients afftected by moderate and severe knee osteoarthritis demonstrating safety and clinical efficacy of the treatment when this autologous cell product is injected in the knee joint and patients evaluated post-operatively after 1 year. However, what do we know about the mechanism that underlies this clinical improvement? This article proposes, for the first time in our opinion, a hypothesis of the mode of action that involves structural and molecular interactions between SVF and infrapatellar fat pad (IFP). As consequence, there would be a re-education of intra-articular adipose tissue, which we consider a key player for the clinical effect observed in the mid and long term mainly due to immuno-regulatory mechanisms. Methods: This is a retrospective and not controlled study that evaluated 50 patients (100 joints) ranging from 50 to 89 years old, separated by age cohorts. Clinical efficacy was assessed using the Lequesne, WOMAC, and VAS scales, by ultrasound control and quantification of the biochemical profiles of synovial fluid. Results: There were no serious adverse effects. All the indexes studied showed a significant clinical improvement after 1-year follow-up for all ages and OA degree groups. This finding was correlated with the ultrasound observations and biochemical data, which show a marked decrease in catabolic and pro-inflammatory molecules (MMP-2, IL-1B, IL-6, and IL-8) and significant increase for anabolic and anti-inflammatory molecules (IGF-1 and IL-10). Conclusions: We conclude that intra-articular SVF infiltration for knee OA treatment is safe and effective during 1 year. We propose that applied SVF cells cause a cascade of molecular and structural events that, through complex interactions between IFP and SVF, re-educating the intra-articular fatty tissue towards a homeostatic, protective, and anti-inflammatory function, which will ultimately promote the restructuring and regeneration of damaged tissues.

Intercellular communication between monocytes/macrophages and cells involved in tissue regeneration, such as mesenchymal stromal cells (MSCs) and primary tissue cells, is essential for tissue regeneration and recovery of homeostasis. Typically, in the final phase of the inflammation-resolving process, this intercellular communication drives an anti-inflammatory immunomodulatory response. To obtain a safe and effective treatment to counteract the cytokine storm associated with a disproportionate immune response to severe infections, including that associated with COVID-19, by means of naturally balanced immunomodulation, our group has standardized the production under GMP-like conditions of a secretome by coculture of macrophages and MSCs. To characterize this proteome, we determined the expression of molecules related to cellular immune response and tissue regeneration, as well as its possible toxicity and anti-inflammatory potency. The results show a specific molecular pattern of interaction between the two cell types studied, with an anti-inflammatory and regenerative profile. In addition, the secretome is not toxic by itself on human PBMC or on THP-1 monocytes and prevents lipopolysaccharide (LPS)-induced growth effects on those cell types. Finally, PRS CK STORM prevents LPS-induced TNF-A and IL-1Β secretion from PBMC and from THP-1 cells at the same level as hydrocortisone, demonstrating its anti-inflammatory potency.

The external popliteal sciatic nerve (EPSN) is the nerve of the lower extremity most frequently affected by compressive etiology. Its superficial and sinuous anatomical course is closely related to other rigid anatomical structures and has an important dynamic neural component. Therefore, this circumstance means that this nerve is exposed to multiple causes of compressive etiology. Despite this fact, there are few publications with extensive case studies dealing with treatment. In this review, we propose to carry out a narrative review of the neuropathy of the EPSN, including an anatomical reminder, its clinical presentation and diagnosis, as well as its surgical and biological approach. The most novel aspect we propose is the review of the possible role of biological factors in the reversal of this situation.

Co-culture of primary or mesenchymal stem cells (MSC) with M2 macrophages produces a very special conditioned medium with a recognizable and stable cytokine pattern (PRS CK STORM), independent of the donor, with unique anti-inflammatory properties. This product can regulate certain pathways of inflammation in an anti-inflammatory manner, including TLR3, TLR4, the inflammasome, and the purinergic system. The anti-inflammatory action of PRS CK STORM is demonstrated both by its composition and by its action in in vitro and in vivo inflammatory models. The study of the mechanism of action showed changes in the pattern of toll-like receptors (TLR) and purinergic receptors, with an increase in the relative expression of mRNA encoding A2a and A3 receptors, together with a decrease in the relative expression of mRNA encoding P2X7 receptors. Second, it mitigated the adverse effects of a systemic inflammatory process in mice, especially in comparison with a known anti-inflammatory drug (Anakinra). Thus, due to its profile in terms of biosafety and efficacy, PRS CK STORM may be a strong candidate to treat inflammatory processes, such as cytokine storm associated with severe infectious processes, including COVID-19.

Our research group has been developing a series of biological drugs produced by coculture techniques with M2-polarized macrophages with different primary tissue cells and/or mesenchymal stromal cells (MSC), generally from fat, to produce anti-inflammatory and anti-fibrotic effects, avoiding the overexpression of pro-inflammatory cytokines by the innate immune system at a given time. One of these products is the drug PRS CK STORM, a medium conditioned by allogenic M2-polarized macrophages, from coculture, with those macrophages M2 with MSC from fat, whose composition, in vitro safety, and efficacy we studied. In the present work, we publish the results obtained in terms of safety (pharmacodynamics and pharmacokinetics) and efficacy of the intravenous application of this biological drug in a murine model of cytokine storm associated with severe infectious processes, including those associated with COVID-19. The results demonstrate the safety and high efficacy of PRS CK STORM as an intravenous drug to prevent and treat the cytokine storm associated with infectious processes, including COVID-19.