Acute kidney injury (AKI) is a fatal medical episode caused by sudden kidney damage or failure, leading to the death of patients within a few hours or days. Previous studies demonstrated that exosomes derived from various mesenchymal stem/stromal cells (MSC-exosomes) have positive effects on renal injuries in multiple experimental animal models of kidney diseases including AKI. However, the mass production of exosomes is a challenge not only in preclinical studies with large animals but also for successful clinical applications. In this respect, tangential flow filtration (TFF) is suitable for good manufacturing practice (GMP)-compliant large-scale production of high-quality exosomes. Until now, no studies have been reported on the use of TFF, but rather ultracentrifugation has been almost exclusively used, to isolate exosomes for AKI therapeutic application in preclinical studies. Here, we demonstrated the reproducible large-scale production of exosomes derived from adipose tissue-derived MSC (ASC-exosomes) using TFF and the lifesaving effect of the ASC-exosomes in a lethal model of cisplatin-induced rat AKI. Our results suggest the possibility of large-scale stable production of ASC-exosomes without loss of function and their successful application in life-threatening diseases.

The stromal vascular fraction (SVF) is a heterogeneous population of stem/stromal cells isolated from perivascular and extracellular matrix (ECM) of adipose tissue complex (ATC). Administration of SVF holds a strong therapeutic potential for regenerative and wound healing medicine applications aimed at functional restoration of tissues damaged by injuries or chronic diseases. SVF is commonly divided into cellular stromal vascular fraction (cSVF) and tissue stromal vascular fraction (tSVF). Cellular SVF is obtained from ATC by collagenase digestion, incubation/isolation, and pelletized by centrifugation. Enzymatic disaggregation may alter the relevant biological characteristics of adipose tissue, while providing release of complex, multiattachment of cell-to-cell and cell-tomatrix, effectively eliminating the bioactive ECM and periadventitial attachments. In many countries, the isolation of cellular elements is considered as a "more than minimal" manipulation, and is most often limited to controlled clinical trials and subject to regulatory review. Several alternative, nonenzymatic methods of adipose tissue processing have been developed to obtain via minimal mechanical manipulation an autologous tSVF product intended for delivery, reducing the procedure duration, lowering production costs, decreasing regulatory burden, and shortening the translation into the clinical setting. Ideally, these procedures might allow for the integration of harvesting and processing of adipose tissue for ease of injection, in a single procedure utilizing a nonexpanded cellular product at the point of care, while permitting intraoperative autologous cellular and tissue-based therapies. Here, we review and discuss the options, advantages, and limitations of the major strategies alternative to enzymatic processing currently developed for minimal manipulation of adipose tissue. STEM CELLS

Vagal paraganglioma is a rare tumor of neural crest origin. Although the literature is in agreement with regard to epidemiology, diagnosis, and tumor biology, there is some controversy over treatment modalities for these patients. We performed a nonrandomized retrospective study in a large single-institution series of patients (n = 19) in whom vagal paraganglioma was diagnosed. General statistics included age, male/female ratio, tumor size, and duration of follow-up. Other variables such as signs and symptoms at presentation, family history, multicentricity, metastatic disease, and secretion of catecholamines were included. CT scan, MRI, and angiography were used in combination for diagnostic purposes as well as for treatment planning. Preoperative embolization was performed in 5 of the more recently treated patients. Current issues regarding the use of preoperative embolization and choice of surgical approach were analyzed. In this article the possibility and sequela of vagus nerve-sparing procedures will be presented. Operative complications and postoperative morbidity related to cranial neuropathies will be discussed. The rationale for performing adjunct procedures, including cricopharyngeal myotomy and vocal fold medialization, to facilitate the rehabilitation of patients with postoperative cranial nerve deficits will be given. Our findings and recommendations will be compared with currently accepted treatment protocols in conjunction with a review of the literature.

The present data indicate that type 1 diabetes mellitus and type 2 diabetes mellitus are not relative or absolute contraindications to microvascular TRAM flap breast reconstruction.