Extracellular Vesicles From Adipose Stem Cells Prevent Muscle Damage and Inflammation in a Mouse Model of Hind Limb Ischemia: Role of Neuregulin-1

Objectives: Critical hindlimb ischemia is a severe consequence of peripheral artery disease. Surgical treatment does not prevent skeletal muscle impairment or improve long-term patient outcomes. The present study investigates the protective/regenerative potential and the mechanism of action of adipose stem cell-derived extracellular vesicles (ASC-EVs) in a mouse model of hindlimb ischemia. Approach and Results: We demonstrated that ASC-EVs exert a protective effect on muscle damage by acting both on tissue microvessels and muscle cells. The genes involved in muscle regeneration were up-regulated in the ischemic muscles of ASC-EV-treated animals. MyoD expression has also been confirmed in satellite cells. This was followed by a reduction in muscle function impairment in vivo. ASC-EVs drive myoblast proliferation and differentiation in the in vitro ischemia/reoxygenation model. Moreover, ASC-EVs have shown an anti-apoptotic effect both in vitro and in vivo. Transcriptomic analyses have revealed that ASC-EVs carry a variety of pro-angiogenic mRNAs, while proteomic analyses have demonstrated an enrichment of NRG1 (neuregulin 1). A NRG1 blocking antibody used in vivo demonstrated that NRG1 is relevant to ASC-EV-induced muscle protection, vascular growth, and recruitment of inflammatory cells. Finally, bioinformatic analyses on 18 molecules that were commonly detected in ASC-EVs, including mRNAs and proteins, confirmed the enrichment of pathways involved in vascular growth and muscle regeneration/protection. Conclusions: This study demonstrates that ASC-EVs display pro-angiogenic and skeletal muscle protective properties that are associated with their NRG1/mRNA cargo. We, therefore, propose that ASC-EVs are a useful tool for therapeutic angiogenesis and muscle protection

[Diagnosis and therapy of low-risk endometrial hyperplasia. Experience with LH-RH-A].

Endometrial hyperplasia is a endometrial condition often found in perimenopausal age. AUB is the most frequent symptom of endometrial hyperplasia. The combination of hysteroscopy and endometrial biopsy is the most suitable approach for the diagnosis of endometrial hyperplasia in symptomatic patients. The Authors have studied endometrial modifications due to LH-RH analogue, a depot formula, in 60 perimenopausal patients with AUB and with hysteroscopic and histologic picture of low-risk endometrial hyperplasia. They report the result of treatment efficacy (disappearance of symptoms and tendency to hypoatrophy of the mucosa). The use of LH-RH A seems to have a good result in the management of oestrogen-dependent gynaecological benign diseases