Targeting Myofibroblasts as a Treatment Modality for Dupuytren Disease.

PURPOSE: Currently, no treatment corrects the contractile nature of Dupuytren myofibroblasts (DMFs) or prevents recurrence following surgery. Antifibrotic and proadipogenic growth factors are released when adipose-derived stem cells (ASCs) are cultured with platelet-rich plasma (PRP), a platelet concentration from whole blood. Reprograming myofibroblasts into adipocytes via growth factors is proposed as a powerful potential tool to target fibrosis. We aimed to assess whether the combination of ASCs and PRP reprograms DMFs into adipocytes in vitro and alters their contractile nature in vivo. METHODS: Normal human dermal fibroblasts (NHDFs) and DMFs from Dupuytren patients were isolated and cocultured with ASCs and PRP either alone or together. Adipocytes were detected by Oil Red O and perilipin staining. DMFs and NHDFs were transplanted into the forepaws of rats (Rowett Nude [rnu/rnu]) and treated with saline, PRP+ASCs, or collagenase Clostridium histolyticum (clinical comparison) 2 months later. After 2 weeks, the tissue was harvested and subjected to Masson trichrome staining, and collagen I and III and alpha-smooth muscle actin detection by immunohistochemistry. RESULTS: Myofibroblasts transform into adipocytes upon coculture with PRP+ASCs. DMFs show increased alpha-smooth muscle actin expression in vivo compared with NHDFs, which is significantly decreased after PRP+ASCs and collagenase Clostridium histolyticum treatments. DMFs induce collagen I and III expressions in rat paws compared with NHDFs, with a type III to I ratio increase. Treatment with PRP+ASC reduced the ratio, but collagenase Clostridium histolyticum did not. CONCLUSIONS: Treating DMFs with PRP+ASCs provides factors that induce myofibroblast to adipocyte transformation. This treatment reduces the contractile phenotype and fibrosis markers in vivo. Future studies should detail the mechanism of this conversion. CLINICAL RELEVANCE: The combination of PRP and ASCs to induce the differentiation of DMFs into adipocytes may serve to limit surgery to a percutaneous contracture release and biological injection, rather than a moderate or radical fasciectomy, and reduce the recurrence of Dupuytren contracture.

Tratamento da resposta inflamatória tardia ao preenchimento de tecidos moles com ácido hialurônico em indivíduo imunizado Moderna após reforço com vacina Pfizer com hialuronidase / Treatment of delayed inflammatory response to hyaluronic acid soft tissue filler in a Pfizer-Boosted Moderna-Vaccinated individual with hyaluronidaseapós reforço com vacina Pfizer com hialuronidase

Apresentamos um caso de hipersensibilidade tardia ao preenchimento à base de ácido hialurônico na face após o reforço da vacina Pfizer em um indivíduo imunizado com Moderna. Este é o primeiro caso conhecido de tratamento da reação de hipersensibilidade tardia com hialuronidase após a vacinação anti-Covid. A hialuronidase é uma opção viável para tratar esta reação, particularmente para pacientes que podem não se favorecer com as opções de tratamento sistémico. Com uma quarta ronda de reforço de vacinas planejada no horizonte, pode haver um aumento da incidência de eventos adversos cutâneos, incluindo a reação discutida.

We present a case of delayed-type hypersensitivity to hyaluronic acid (HA)-based filler on the face following the Pfizer booster in a Moderna-vaccinated individual. It is the first known case of treatment of the delayed-type hypersensitivity reaction with hyaluronidase following Covid vaccination. Hyaluronidase is a viable option to treat this reaction, particularly for patients who may not benefit from systemic treatment options. With an anticipated fourth round of vaccine boosters on the horizon, there may be an increased incidence of cutaneous adverse events, including the reaction discussed.