The skin’s recognised functions may undergo physiological alterations due to ageing, manifesting as varying degrees of facial wrinkles, diminished tautness, density, and volume. Additionally, these functions can be disrupted (patho)physiologically through various physical and chemical injuries, including surgical trauma, accidents, or chronic conditions like ulcers associated with diabetes mellitus, venous insufficiency, or obesity. Advancements in therapeutic interventions that boost the skin’s innate regenerative abilities could significantly enhance patient care protocols. The application of Platelet-Rich Plasma (PRP) is widely recognized for its aesthetic and functional benefits to the skin. Yet, the endorsement of PRP’s advantages often borders on the dogmatic, with its efficacy commonly ascribed solely to the activation of fibroblasts by the factors contained within platelet granules. PRP therapy is a cornerstone of regenerative medicine which involves the autologous delivery of conditioned plasma enriched by platelets. This is achieved by centrifugation, removing erythrocytes while retaining platelets and their granules. Despite its widespread use, the precise sequences of cellular activation, the specific cellular players, and the molecular machinery that drive PRP-facilitated healing are still enigmatic. There is still a paucity of definitive and robust studies elucidating these mechanisms. In recent years, telocytes (TCs)—a unique dermal cell population—have shown promising potential for tissue regeneration in various organs, including the dermis. TCs’ participation in neo-angiogenesis, akin to that attributed to PRP, and their role in tissue remodelling and repair processes within the interstitia of several organs (including the dermis), offer intriguing insights. Their potential to contribute to, or possibly orchestrate, the skin regeneration process following PRP treatment has elicited considerable interest. Therefore, pursuing a comprehensive understanding of the cellular and molecular mechanisms at work, particularly those involving TCs, their temporal involvement in structural recovery following injury, and the interconnected biological events in skin wound healing and regeneration represents a compelling field of study.

Fifteen years after their discovery, telocytes (TCs) are yet perceived as a new stromal cell type. Their presence was initially documented peri-digestively, and gradually throughout the interstitia of many (non-)cavitary mammalian, human, and avian organs, including skin. Each time, TCs proved to be involved in diverse spatial relations with elements of interstitial (ultra)structure (blood vessels, nerves, immune cells, etc.). To date, transmission electron microscopy (TEM) remained the single main microscopic technique able to correctly and certainly attest TCs by their well-acknowledged (ultra)structure. In skin, dermal TCs reiterate almost all (ultra)structural features ascribed to TCs in other locations, with apparent direct implications in skin physiology and/or pathology. TCs’ uneven distribution within skin, mainly located in stem cell niches, suggests involvement in either skin homeostasis or dermatological pathologies. On the other hand, different skin diseases involve different patterns of disruption of TCs’ structure and ultrastructure. TCs’ cellular cooperation with other interstitial elements, their immunological profile, and their changes during remission of diseases suggest their role(s) in tissue regeneration/repair processes. Thus, expanding the knowledge on dermal TCs could offer new insights into the natural skin capacity of self-repairing. Moreover, it would become attractive to consider that augmenting dermal TCs’ presence/density could become an attractive therapeutic alternative for treating various skin defects.

For more than 40 years, autologous platelet concentrates have been used in clinical medicine. Since the first formula used, namely platelet-rich plasma (PRP), other platelet concentrates have been experimented with, including platelet-rich fibrin and concentrated growth factor. Platelet concentrates have three standard characteristics: they act as scaffolds, they serve as a source of growth factors and cytokines, and they contain live cells. PRP has become extensively used in regenerative medicine for the successful treatment of a variety of clinical (non-)dermatological conditions like alopecies, acne scars, skin burns, skin ulcers, muscle, cartilage, and bone repair, and as an adjuvant in post-surgery wound healing, with obvious benefits in terms of functionality and aesthetic recovery of affected tissues/organs. These indications were well documented, and a large amount of evidence has already been published supporting the efficacy of this method. The primordial principle behind minimally invasive PRP treatments is the usage of the patient’s own platelets. The benefits of the autologous transplantation of thrombocytes are significant, representing a fast and economic method that requires only basic equipment and training, and it is biocompatible, thus being a low risk for the patient (infection and immunological reactions can be virtually disregarded). Usually, the structural benefits of applying PRP are attributed to fibroblasts only, as they are considered the most numerous cell population within the interstitium. However, this apparent simplistic explanation is still eluding those different types of interstitial cells (distinct from fibroblasts) that are residing within stromal tissue, e.g., telocytes (TCs). Moreover, dermal TCs have an already documented potential in angiogenesis (extra-cutaneous, but also within skin), and their implication in skin recovery in a few dermatological conditions was attested and described ultrastructurally and immunophenotypically. Interestingly, PRP biochemically consists of a series of growth factors, cytokines, and other molecules, to which TCs have also proven to have a positive expression. Thus, it is attractive to hypothesize and to document any tissular collaboration between cutaneous administered PRP and local dermal TCs in skin recovery/repair/regeneration. Therefore, TCs could be perceived as the missing link necessary to provide a solid explanation of the good results achieved by administering PRP in skin-repairing processes.

Cardiac interstitium is a complex and dynamic environment, vital for normal cardiac structure and function. Telocytes are active cellular players in regulating main events that feature myocardial homeostasis and orchestrating its involvement in heart pathology. Despite the great amount of data suggesting (microscopically, proteomically, genetically, etc.) the implications of telocytes in the different physiological and reparatory/regenerative processes of the heart, understanding their involvement in realizing the heart’s mature cytoarchitecture is still at its dawn. Our scrutiny of the recent literature gave clearer insights into the implications of telocytes in the WNT signaling pathway, but also TGFB and PI3K/AKT pathways that, inter alia, conduct cardiomyocytes differentiation, maturation and final integration into heart adult architecture. These data also strengthen evidence for telocytes as promising candidates for cellular therapies in various heart pathologies.

Background and Objectives: Cutaneous melanoma (CM) is one of the most aggressive skin malignancies due to its rapid progression and high therapeutic resistance. Growing evidence demonstrates that the tumor microenvironment (TME)—comprising diverse immune, stromal, vascular, and epidermal cell populations alongside various cytokines and growth factors, as well as extracellular matrix (ECM) components—plays a crucial role in tumor heterogeneity, metastatic potential, and response to therapy. This review aims to synthesise current knowledge on the cellular and non-cellular constituents of the CM microenvironment and clarify their contributions to tumor progression, immune evasion, and treatment resistance. Materials and Methods: We conducted a narrative review of recent experimental, clinical, and translational studies investigating melanoma–microenvironment interactions, integrating evidence from in vitro, in vivo, and human tissue analyses. Results: Melanoma exhibits marked intra-tumoral heterogeneity driven by genetic, epigenetic, and microenvironmental influences. Cancer-associated fibroblasts, adipocytes, endothelial cells, and keratinocytes are reprogrammed by melanoma cells to promote invasion, angiogenesis, and metastasis. Immune subsets play divergent roles: neutrophils, M2 macrophages, myeloid-derived suppressor cells, and tolerogenic dendritic cells foster immune suppression, while lymphocytes—particularly CD8⁺ T cells, TFH cells, and B cells —are associated with improved outcomes but often become dysfunctional. ECM remodeling, including collagen deposition, integrin signaling, and increased matrix stiffness, actively remodels the tissue to support tumor growth and immune evasion. Hypoxia-inducible factor (HIF)-mediated signaling drives cell dedifferentiation, angiogenesis, and metabolic changes that contribute to treatment resistance. Consequently, emerging therapeutic strategies are moving beyond targeting tumor cells alone to focus on modulating TME components, counteracting immunosuppression, hypoxia, metabolic reprogramming, and extracellular vesicle signaling. Conclusions: The TME profoundly modulates tumor behavior and therapeutic response. A deeper understanding of the reciprocal interactions between melanoma cells and their microenvironmental components may enable the development of more effective strategies for early detection, prognosis, and personalized therapies.