MiRNA regulated therapeutic potential of the stromal vascular fraction: Current clinical applications - A systematic review

Abstract

Introduction: The stromal vascular fraction (SVF) is a heterogeneous population of cells that, interacting with each other, can affect the processes of regeneration, angiogenesis, and immunomodulation. Over the past 20 years, there has been a trend towards an increase in the number of clinical studies on the therapeutic use of SVF. MicroRNAs (miRNAs) are also important regulators of cellular function and they have been shown to be involved in SVF cellular component function. The purpose of this study was to analyze existing clinical studies on the therapeutic use of SVF including the role of miRNAs in the regulation of the function of the cellular component of SVF as an anti-inflammatory, pro-angiogenic and cell differentiation activity.

Methods: The search strategy was to use material from the clinicaltrials.gov website, which focused on the key term "Stromal vascular fraction", and the inclusion and exclusion criteria were divided into two stages.

Results: By August 2022, there were 149 registered clinical trials. Most studies belong to either Phase 1-2 (49.37%), Phase 1 (25.32%) or Phase 2 (22.78%). Most of them focused in the fields of traumatology, neurology/neurosurgery, endocrinology, vascular surgery, and immunology. However, only 8 clinical trials had published results. All of clinical trials have similar preparation methods and 8 clinical trials have positive results with no serious adverse effects.

Conclusions: There appears to be a wide potential for the clinical use of SVF without reports of serious side effects. Many preclinical and clinical studies are currently underway on the use of SVF, and their future results will help to further explore their therapeutic potential. Nevertheless, there are not many studies on the role of miRNAs in the SVF microenvironment; however, this topic is very important for further study of the clinical application of SVF, including safety, in various human diseases.

Keywords: Clinical trial; Epidemiology; Stromal vascular fraction; Therapy; miRNA.

Fig. 1

Statistics of registered clinical trials for testing the clinical potential of the stromal vascular fraction (SVF) in accordance with the dynamics of temporary (year) registrations since the start of the first clinical trial.

Fig. 2

Distribution of registered clinical trials on the use of stromal vascular fraction (SVF) by phases.

Fig. 3

Distribution of registered clinical trials on the use of stromal vascular fraction (SVF) depending on progress.

Fig. 4

Distribution of registered clinical trials on the use of stromal vascular fraction (SVF) by localization in the world.

Fig. 5

Understanding stromal vascular fraction (SVF) cell biology by regulating miRNAs specific for cells component of SVF that regulate gene expression by targeting transcription factors associated to different processes. Note: FABP4, fatty acid binding protein 4; TNF-α, tumor necrosis factor-α; STAT3, signal transducer and activator of transcription 3; VEGF, vascular endothelial growth factor; FGF-β, fibroblast growth factor-β; HGF, hepatocyte growth factor; PDGFB, platelet-derived growth factor subunit B; TGF-β, transforming growth factor-β; JAK3, tyrosine-protein kinase; TLR2/3, toll-like receptor 2/3; IL-4, interleukin-4; KLF4/5, kruppel-like factor 4/5; SRF, serum response factor.

Fig. 6

Adipose tissue-derived stem cells (ADSCs) release exosomes with a miRNAs cargo by targeting transcription factors associated to different human diseases. These exosomal miRNAs can be used to develop new and effective therapies.