The Biological Role of Platelet Derivatives in Regenerative Aesthetics.

Bioproducts derived from platelets have been extensively used across various medical fields, with a recent notable surge in their application in dermatology and aesthetic procedures. These products, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), play crucial roles in inducing blood vessel proliferation through growth factors derived from peripheral blood. PRP and PRF, in particular, facilitate fibrin polymerization, creating a robust structure that serves as a reservoir for numerous growth factors. These factors contribute to tissue regeneration by promoting cell proliferation, differentiation, and migration and collagen/elastin production. Aesthetic medicine harnesses these effects for diverse purposes, including hair restoration, scar treatment, striae management, and wound healing. Furthermore, these biological products can act as adjuvants with other treatment modalities, such as laser therapy, radiofrequency, and microneedling. This review synthesizes the existing evidence, offering insights into the applications and benefits of biological products in aesthetic medicine.

Cannabidiol for musculoskeletal regenerative medicine.

Chronic musculoskeletal (MSK) pain is one of the most prevalent causes, which lead patients to a physician's office. The most common disorders affecting MSK structures are osteoarthritis, rheumatoid arthritis, back pain, and myofascial pain syndrome, which are all responsible for major pain and physical disability. Although there are many known management strategies currently in practice, phytotherapeutic compounds have recently begun to rise in the medical community, especially cannabidiol (CBD). This natural, non-intoxicating molecule derived from the cannabis plant has shown interesting results in many preclinical studies and some clinical settings. CBD plays vital roles in human health that go well beyond the classic immunomodulatory, anti-inflammatory, and antinociceptive properties. Recent studies demonstrated that CBD also improves cell proliferation and migration, especially in mesenchymal stem cells (MSCs). The foremost objective of this review article is to discuss the therapeutic potential of CBD in the context of MSK regenerative medicine. Numerous studies listed in the literature indicate that CBD possesses a significant capacity to modulate mammalian tissue to attenuate and reverse the notorious hallmarks of chronic musculoskeletal disorders (MSDs). The most of the research included in this review report common findings like immunomodulation and stimulation of cell activity associated with tissue regeneration, especially in human MSCs. CBD is considered safe and well tolerated as no serious adverse effects were reported. CBD promotes many positive effects which can manage detrimental alterations brought on by chronic MSDs. Since the application of CBD for MSK health is still undergoing expansion, additional randomized clinical trials are warranted to further clarify its efficacy and to understand its cellular mechanisms.

Metabolic syndrome and subchondral bone alterations: The rise of osteoarthritis - A review.

Metabolic syndrome (MS) has become one of the top major health burdens for over three decades not only due to its effects on cardiovascular health but also its implications in orthopedics. Extensive research has shown that MS is tightly linked to osteoarthritis and inflammation, a process which appears to primarily occur in the subchondral bone via the incidence of bone-marrow lesions (BMLs). Numerous studies identify obesity, dyslipidemia, insulin resistance and hypertension as the top metabolic risk factors, the so-called "deadly quartet". These factors are responsible for the disruptive physiological processes that culminate in detrimental alterations within the subchondral bone, cartilage damage and, overall, the predominant pro-inflammatory joint microenvironment. Although it has long been thought that osteoarthritis was limited to the cartilage component of the joint, other studies indicate that the disease may originate from the harmful alterations that occur primarily in the subchondral bone, especially via means of vascular pathology. Since metabolic risk factors are manageable to a certain extent, it is therefore possible to decelerate the progression of OA and mitigate its devastating effects on the subchondral bone and subsequent articular cartilage damage. METHODS: Literature was reviewed using PubMed and Google Scholar in order to find a correlation between metabolic syndrome and osteoarthritic progression. The investigation included a combination of nomenclature such as: "metabolic syndrome", "obesity", "insulin resistance", "hypertension", "dyslipidemia", "low-grade systemic inflammation", "osteoarthritis", "subchondral bone", "cartilage" and "inflammatory biomarkers". CONCLUSION: Based on several studies, there seems to be a significant association between The Deadly Quartet (metabolic syndrome), dysregulation of both pro- and anti-inflammatory biomarkers, and osteoarthritic progression arising from unbridled systemic inflammation.

FGF2 Stimulates the Growth and Improves the Melanocytic Commitment of Trunk Neural Crest Cells.

Neural crest cells (NCCs) comprise a population of multipotent progenitors and stem cells at the origin of the peripheral nervous system (PNS) and melanocytes of skin, which are profoundly influenced by microenvironmental factors, among which is basic fibroblast growth factor 2 (FGF2). In this work, we further investigated the role of this growth factor in quail trunk NC morphogenesis and demonstrated its huge effect in NCC growth mainly by stimulating cell proliferation but also reducing cell death, despite that NCC migration from the neural tube explant was not affected. Moreover, following FGF2 treatment, reduced expression of the early NC markers Sox10 and FoxD3 and improved proliferation of HNK1-positive NCC were observed. Since these markers are involved in the regulation of glial and melanocytic fate of NC, the effect of FGF2 on NCC differentiation was investigated. Therefore, in the presence of FGF2, increased proportions of NCCs positives to the melanoblast marker Mitf as well as NCCs double stained to Mitf and BrdU were recorded. In addition, treatment with FGF2, followed by differentiation medium, resulted in increased expression of melanin and improved proportion of melanin-pigmented melanocytes without alteration in the glial marker Schwann myelin protein (SMP). Taken together, these data further reveal the important role of FGF2 in NCC proliferation, survival, and differentiation, particularly in melanocyte development. This is the first demonstration of FGF2 effects in melanocyte commitment of NC and in the proliferation of Mitf-positive melanoblasts. Elucidating the differentiation process of embryonic NCCs brings us a step closer to understanding the development of the PNS and then undertaking the search for advanced technologies to prevent, or treat, injuries caused by NC-related disorders, also known as neurocristopathies.

EGF-FGF2 stimulates the proliferation and improves the neuronal commitment of mouse epidermal neural crest stem cells (EPI-NCSCs).

Epidermal neural crest stem cells (EPI-NCSCs), which reside in the bulge of hair follicles, are attractive candidates for several applications in cell therapy, drug screening and tissue engineering. As suggested remnants of the embryonic neural crest (NC) in an adult location, EPI-NCSCs are able to generate a wide variety of cell types and are readily accessible by a minimally invasive procedure. Since the combination of epidermal growth factor (EGF) and fibroblast growth factor type 2 (FGF2) is mitogenic and promotes the neuronal commitment of various stem cell populations, we examined its effects in the proliferation and neuronal potential of mouse EPI-NCSCs. By using a recognized culture protocol of bulge whiskers follicles, we were able to isolate a population of EPI-NCSCs, characterized by the migratory potential, cell morphology and expression of phenotypic markers of NC cells. EPI-NCSCs expressed neuronal, glial and smooth muscle markers and exhibited the NC-like fibroblastic morphology. The treatment with the combination EGF and FGF2, however, increased their proliferation rate and promoted the acquisition of a neuronal-like morphology accompanied by reorganization of neural cytoskeletal proteins ßIII-tubulin and nestin, as well as upregulation of the pan neuronal marker ßIII-tubulin and down regulation of the undifferentiated NC, glial and smooth muscle cell markers. Moreover, the treatment enhanced the response of EPI-NCSCs to neurogenic stimulation, as evidenced by induction of GAP43, and increased expression of Mash-1 in neuron-like cell, both neuronal-specific proteins. Together, the results suggest that the combination of EGF-FGF2 stimulates the proliferation and improves the neuronal potential of EPI-NCSCs similarly to embryonic NC cells, ES cells and neural progenitor/stem cells of the central nervous system and highlights the advantage of using EGF-FGF2 in neuronal differentiation protocols.

Dermal substitutes support the growth of human skin-derived mesenchymal stromal cells: potential tool for skin regeneration.

New strategies for skin regeneration are needed in order to provide effective treatment for cutaneous wounds and disease. Mesenchymal stem cells (MSCs) are an attractive source of cells for tissue engineering because of their prolonged self-renewal capacity, multipotentiality, and ability to release active molecules important for tissue repair. In this paper, we show that human skin-derived mesenchymal stromal cells (SD-MSCs) display similar characteristics to the multipotent MSCs. We also evaluate their growth in a three-dimensional (3D) culture system with dermal substitutes (Integra and Pelnac). When cultured in monolayers, SD-MSCs expressed mesenchymal markers, such as CD105, Fibronectin, and α-SMA; and neural markers, such as Nestin and ßIII-Tubulin; at transcriptional and/or protein level. Integra and Pelnac equally supported the adhesion, spread and growth of human SD-MSCs in 3D culture, maintaining the MSC characteristics and the expression of multilineage markers. Therefore, dermal substitutes support the growth of mesenchymal stromal cells from human skin, promising an effective tool for tissue engineering and regenerative technology.

O papel das enzimas CYP2A na susceptibilidade ao câncer do esôfago e sua regulação / The role of CYP2A enzymes in susceptibility to esophageal cancer and its regulation

As nitrosaminas são pré-carcinógenos presentes no cigarro e em alguns alimentos e são os únicos compostos capazes de induzir tumores no esôfago de animais experimentais. Uma vez que as nitrosaminas somente se tornam cancerígenos após serem metabolizadas por enzimas CYP, a presença de um CYP capaz de ativá-las é fundamental para a susceptibilidade tecidual à indução de tumores por estes carcinógenos. A indução de tumores esofágicos pelas nitrosaminas varia entre os animais experimentais, sendo o rato a espécie mais susceptível. Em 2001, nosso grupo identificou o CYP2A3 como sendo a principal enzima responsável pela ativação da NDEA no esôfago de ratos. Por outro lado, nenhuma das nitrosaminas testadas até o momento induz tumores esofágicos no hamster, sendo o fígado o principal órgão-alvo. Com o objetivo de achar uma explicação mecanística para a resistência do esôfago do hamster às nitrosaminas, neste trabalho nós caracterizamos a expressão de enzima CYP2A no esôfago deste animal e comparamos o metabolismo da NDEA entre esôfago e fígado. Mostramos que tanto o esôfago quanto o fígado expressam os mRNAs dos CYP2A8, CYP2A9 e CYP2A16. A expressão protéica, no entanto, é diferente entre os tecidos. Os resultados de Western blotting mostram que, apesar do esôfago e fígado expressarem uma isoforma em comum, o esôfago expressa uma segunda isoforma que não é presente no fígado, enquanto o fígado expressa uma proteína que não é detectada no esôfago. Surpreendentemente, também detectamos uma alta ativação da NDEA pelos microssomos esofágicos. Porém, a eficiência catalítica desta reação foi cerca de 40 vezes menor do que a detectada nos microssomos hepáticos. Um anticorpo anti-CYP2A6 humano foi capaz de inibir o metabolismo da NDEA em microssomos esofágicos, mas não hepáticos. A diferença na eficiência catalítica da reação de NDEA entre esôfago e fígado pode explicar porque as nitrosaminas nunca induzem tumores esofágicos em hamsters. Devido ao papel dos CYP2A...

Nitrosamines are pre-carcinogens found in food and cigarette smoke and are the only compounds known to induce esophageal tumors in experimental animals. Nitrosamines become active carcinogens tumors only after being metabolized by CYP enzymes. Therefore, CYP expression is essential for tissue-specific tumor induction by nitrosamines. Esophageal tumor induction by nitrosamines varies amongst experimental animals, with the rat being the most sensitive species. We have previously shown that CYP2A3 is expressed in the rat esophagus and that CYP2A3 is responsible for NDEA activation in this tissue. On the other hand, none of the nitrosamines tested so far induces esophageal tumors in hamsters, with the liver being the main target-organ for nitrosamine induced tumors. In order to find a mechanistic explanation for its esophageal resistance to nitrosamines, we have characterized CYP2A expression in hamster esophagus and liver and compared NDEA metabolism between these tissues. Hamster esophagus and liver express CYP2A8, CYP2A9 and CYP2A16 mRNAs. However, protein expression is different between the tissues, and our Western blotting results showed that, whereas both the esophagus and liver express two CYP2A isoforms each, only one of the isoforms is similar in both tissues. Surprisingly, we have detected a high NDEA activation in the esophageal microsomes. However, the catalytic efficiency for this reaction was about 40-fold lower than the one detected for hepatic microsomes. An antibody against human CYP26 was able to inhibit NDEA in hamster esophageal, but not liver microsomes. The difference in the catalytic efficiency towards NDEA metabolism between esophagus and liver could help to explain hamster esophageal resistance to nitrosamines. CYP2A inhibition could be a promising approach in chemoprevention, leading to a reduction of the diseases associated with tobacco smoking. There are few data about CYP2A inhibition in experimental animals...

Hamster exhibits major differences in organ-specific metabolism of the esophageal carcinogen N-nitrosodiethylamine.

Nitrosamines are carcinogens that require metabolic activation by CYP enzymes in order to exert their carcinogenic effect. Species differences exist in their esophageal carcinogenic potency, with the rat being the most sensitive and the Syrian hamster a resistant species. In the latter, the liver is the main target organ. This difference does not apply to directly acting N-nitroso compounds, suggesting that tissue-specific metabolic activation is involved in hamster esophageal resistance to nitrosamines. We have previously shown that Cytochrome P450 2A3 (CYP2A3) is responsible for N-nitrosodiethylamine activation in the rat esophagus. In order to find a mechanistic explanation for the resistance of hamster esophagus for nitrosamines, we have compared the metabolism of NDEA between esophagus and liver of the hamster. Hamster esophagus is capable of activating NDEA (K(m)=1.02+/-0.44microM and V(max)=1.96+/-0.26nmol acetaldehyde/min/mg microsomal protein). However, the hamster liver showed a 40-fold higher catalytic efficiency (V(max)/K(m)) towards NDEA metabolism compared with its esophagus. Hamster esophagus expresses CYP2A8, CYP2A9 and CYP2A16, but not CYP2E1. An antibody against human CYP2A6 was able to inhibit NDEA metabolism in hamster esophageal, but not liver microsomes. Our results suggest that in the hamster esophagus, but not in the liver, most of the NDEA is metabolized by CYP2A enzymes, but with a rather poor efficiency when compared to the liver. This is in accordance with previous results showing that for the hamster, the main target organ of NDEA is the liver.