Intraoperative Strategies for Minimal Manipulation of Autologous Adipose Tissue for Cell- and Tissue-Based Therapies: Concise Review

Abstract

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

Tuning Adipogenic Differentiation in ADSCs by Metformin and Vitamin D: Involvement of miRNAs

“…In the niche in which they reside, ADSCs are responsible for maintaining adipose tissue physiology and its renewal [ 27 ]. Moreover, in recent years, different kind of isolation procedures of these cells from the stromal vascular fraction (SVF) have been optimized in order to easily obtain a high yield of stem cells with a higher differentiation potential, as compared to stem cells from other sources [ 25 , 28 , 29 , 30 ]. In physiological conditions, ADSCs are involved in the process of adipogenesis, differentiating in pre-adipocytes and mature adipocytes maintaining the homeostasis of adipose tissue [ 31 ].…”

Biological Features Implies Potential Use of Autologous Adipose-Derived Stem/Progenitor Cells in Wound Repair and Regenerations for the Patients with Lipodystrophy

“…As we recently reported [13], it is evident that autologous stem cell therapy is able to retrieve the abrogated function of skin. Furthermore, tissue regeneration using ADSCs involves indirect effects, which accelerate wound healing through secreting growth factors [46,47,48,49,50,51,52]. Thus, autologous ADSC therapy could be a promising solution for subcutaneous adipose-tissue damage, including lipodystrophy in the patients receiving HAART.…”

Bone Tissue Regeneration in the Oral and Maxillofacial Region: A Review on the Application of Stem Cells and New Strategies to Improve Vascularization

“…However, the MF procurement does not avoid the regulatory burden of using stem cell preparations obtained by enzymatic digestion, which are considered "more than minimally manipulated" by the FDA and the European counterpart the EMA. Therefore, recently, much effort was put in the development of mechanical disruption of the tissue creating microfragmented adipose tissue/nanofat (MFAT/N-FAT) (reviewed in Trivisonno et al's study [125]).…”