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Concise Review: Fat and Furious: Harnessing the Full Potential of Adipose-Derived Stromal Vascular Fraction.

ABSTRACT: Due to their capacity to self-renew, proliferate and generate multi-lineage cells, adult-derived stem cells offer great potential for use in regenerative therapies to stop and/or reverse degenerative diseases such as diabetes, heart failure, Alzheimer's disease and others. However, these subsets of cells can be isolated from different niches, each with differing potential for therapeutic applications. The stromal vascular fraction (SVF), a stem cell enriched and adipose-derived cell population, has garnered interest as a therapeutic in regenerative medicine due to its ability to secrete paracrine factors that accelerate endogenous repair, ease of accessibility and lack of identified major adverse effects. Thus, one can easily understand the rush to employ adipose-derived SVF to treat human disease. Perhaps faster than any other cell preparation, SVF is making its way to clinics worldwide, while critical preclinical research needed to establish SVF safety, efficacy and optimal, standardized clinical procedures are underway. Here, we will provide an overview of the current knowledge driving this phenomenon, its regulatory issues and existing studies, and propose potential unmapped applications. Stem Cells Translational Medicine 2017;6:1096-1108.

SUBMITTER: Dykstra JA

PROVIDER: S-EPMC5388064 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Concise Review: Fat and Furious: Harnessing the Full Potential of Adipose-Derived Stromal Vascular Fraction.

Dykstra Jordan A JA Facile Tiffany T Patrick Ryan J RJ Francis Kevin R KR Milanovich Samuel S Weimer Jill M JM Kota Daniel J DJ

Stem cells translational medicine 20170106 4

Due to their capacity to self-renew, proliferate and generate multi-lineage cells, adult-derived stem cells offer great potential for use in regenerative therapies to stop and/or reverse degenerative diseases such as diabetes, heart failure, Alzheimer's disease and others. However, these subsets of cells can be isolated from different niches, each with differing potential for therapeutic applications. The stromal vascular fraction (SVF), a stem cell enriched and adipose-derived cell population, ...[more]

PMID: 28186685

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Project description:Human adipose-derived stromal vascular fraction (hSVF) cells are an easily accessible, heterogeneous cell system that can spontaneously self-assemble into functional microvasculatures in vivo. However, the mechanisms underlying vascular self-assembly and maturation are poorly understood, therefore we utilized an in vitro model to identify potential in vivo regulatory mechanisms. We utilized passage one (P1) hSVF because of the rapid UEA1+ endothelium (EC) loss at even P2 culture. We exposed hSVF cells to a battery of angiogenesis inhibitors and found that the pan-Wnt inhibitor IWP2 produced the most significant hSVF-EC networking decrease (~25%). To determine which Wnt isoform(s) and receptor(s) may be involved, hSVF was screened by PCR for isoforms associated with angiogenesis, with only WNT5A and its receptor, FZD4, being expressed for all time points observed. Immunocytochemistry confirmed Wnt5a protein expression by hSVF. To see if Wnt5a alone could restore IWP2-induced EC network inhibition, recombinant human Wnt5a (0-150 ng/ml) was added to IWP2-treated cultures. The addition of rhWnt5a significantly increased EC network area and significantly decreased the ratio of total EC network length to EC network area compared to untreated controls. To determine if Wnt5a mediates in vivo microvascular self-assembly, 3D hSVF constructs containing an IgG isotype control, anti-Wnt5a neutralizing antibody or rhWnt5a were implanted subcutaneously for 2w in immune compromised mice. Compared to IgG controls, anti-Wnt5a treatment significantly reduced vessel length density by ~41%, while rhWnt5a significantly increased vessel length density by ~62%. However, anti-Wnt5a or rhWnt5a did not significantly affect the density of segments and nodes, both of which measure vascular complexity. Taken together, this data demonstrates that endogenous Wnt5a produced by hSVF plays a regulatory role in microvascular self-assembly in vivo. These findings also suggest that manipulating Wnt signaling could enhance control of hSVF vascularization in tissue engineering applications.

Project description:BackgroundSystemic Sclerosis in the hand is characteristically evidenced by Raynaud's phenomenon, fibrosis of the skin, tendons, ligaments, and joints as well as digital ulcers with prolonged healing. Current medical treatment does not always cure these complications. Local adipose-derived stromal vascular fraction administration into the hands has been proposed as an emerging treatment due to its regenerative properties. The objective of this randomized controlled clinical trial was to evaluate the safety and clinical effects of fat micrografts plus adipose derived-stromal vascular fraction administration into the hands of patients with systemic sclerosis.MethodsThis was an open-label, monocentric, randomized controlled study. Twenty patients diagnosed with systemic sclerosis were assigned to the experimental or control group. Fat micrografts plus the adipose derived-stromal vascular fraction were injected into the right hand of experimental group patients. The control group continued to receive only medical treatment. Demographic, serologic data and disease severity were recorded. Digital oximetry, pain, Raynaud phenomenon, digital ulcers number, mobility, thumb opposition, vascular density of the nail bed, skin affection of the hand, serologic antibodies, hand function, and quality of life scores were evaluated in both groups.ResultsThe results of the intervention were analyzed with the Wilcoxon rank test, and the differences between the control and experimental groups at 0 days and 168 days were analyzed with the Mann-Whitney U test. Adverse events were not observed in both groups. At the end of the study, statistically significant improvements were observed in pain levels (p<0.05) and number of digital ulcers (p<0.01) in the experimental vs control group.ConclusionThe injection of adipose derived-stromal vascular fraction plus fat micrografts is a reproducible, and safe technique. Pain and digital ulcers in the hands of patients with systemic sclerosis can be treated with this technique plus conventional medical treatment.

Project description:BackgroundAdipose-derived stromal vascular fraction (SVF) cells are a mixed cell population that includes cells with multilineage potential, similar to bone marrow-derived mesenchymal stem cells. Our purpose is to investigate the influence of SVF cells in patients with knee osteoarthritis (OA) and the short-term treatment effects.MethodsFifty-seven patients were enrolled and treated with intra-articular injection of 2.5 × 107 SVF cells into the knee joint between September 2017 and March 2018. All patients were followed up for 12 months or longer. Mean age at treatment and follow-up period were 69.4 ± 6.9 years and 13.7 ± 2.0 months, respectively. The mean preoperative hip-knee-ankle angle was 6.7 ± 3.6°. SVF cells were prepared using the Celution®800/CRS system from the patients' abdominal or breech subcutaneous fat. The mean SVF cell viability was 90.6 ± 2.7%. Clinical evaluations were performed for range of motion, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain, and the Knee injury and Osteoarthritis Score (KOOS). Imaging evaluations, which included the hip-knee-ankle angle assessed via radiography, and T2 mapping value using a 1.5-T magnetic resonance imaging unit were also assessed. Both clinical and imaging evaluations were performed preoperatively, 1, 3, 6, and 12 months postoperatively, and compared among all timepoints (p < 0.05).ResultsKnee extension angle at 6 and 12 months postoperatively was significantly better than the preoperative angle. Total WOMAC, VAS, and KOOS scores at 1, 3, 6 and 12 months postoperatively were significantly better than preoperative scores. There was no significant difference in hip-knee-ankle angle among the five time periods. T2 mapping values of lateral femur and tibia were significantly higher 12 months postoperatively than preoperatively.ConclusionsThe short-term clinical effects of intra-articular SVF cell injection on knee OA were excellent. Intra-articular SVF cell injection is a novel and innovative approach for treating patients with knee OA.

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Concise Review: Fat and Furious: Harnessing the Full Potential of Adipose-Derived Stromal Vascular Fraction.

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Concise Review: Fat and Furious: Harnessing the Full Potential of Adipose-Derived Stromal Vascular Fraction.

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