Autologous Stromal Vascular Fraction in the Intravenous Treatment of End-Stage Chronic Obstructive Pulmonary Disease: A Phase I Trial of Safety and Tolerability

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) is a consistently progressive, ultimately fatal disease for which no treatment exists capable of either reversing or even interrupting its course. It afflicts more than 5% of the population in many countries, and it accordingly represents the third most frequent cause of death in the US, where it accounts for more than 600 billion in health care costs, morbidity, and mortality. Adipose tissue contains within its stromal compartment a high abundance of adipose stem/stromal cells (ASCs), which can be readily separated from the adipocyte population by methods which require less than 2 h of processing time and yield a concentrated cellular preparation termed the stromal vascular fraction (SVF). The SVF contains all cellular elements of fat, excluding adipocytes. Recent clinical studies have begun to explore the feasibility and safety of the local injection or intravascular delivery of SVF or more purified populations of ASCs derived by culture protocols. Several pre-clinical studies have demonstrated a remarkable ability of ASC to nearly fully ameliorate the progress of emphysema due to cigarette smoke exposure as well as other causes. However, no prior clinical studies have evaluated the safety of administration of either ASC or SVF in subjects with COPD. We hypothesized that harvest, isolation, and immediate intravenous infusion of autologous SVF would be feasible and safe in subjects with COPD; and that such an approach, if ultimately determined to be efficacious as well as safe, would provide a highly practical method for treatment of COPD.MethodsIn this study, an initial phase I trial evaluating the early and delayed safety of SVF infusion was performed. Twelve subjects were enrolled in the study, in which adipose tissue was harvested using standard liposuction techniques, followed by SVF isolation and intravenous infusion of 150 - 300 million cells. Standardized questionnaires were administered to study feasibility as well as immediate and delayed outcomes and adverse events as primary endpoints. Secondary endpoints included subjective wellness and attitudes towards the procedure, as well as willingness to undergo the procedure a second time. The follow-up time ranged from 3 to 12 months, averaging 12 months.ResultsOf the 12 subjects, only one experienced an immediate adverse event, related to bruising from the liposuction. No observed pulmonary or cardiac issues were observed as related to the procedure. There were no deaths over the 12-month study period, and none identified in the subsequent telephonic follow-up. Attitudes toward the procedure were predominantly positive, and 92% of the study subjects expressed a desire to undergo the procedure a second time.ConclusionsThis study is the first to demonstrate safety of SVF infusion in humans with serious pulmonary disease. Specifically, the use of intravenous infusion as a route to achieve pulmonary cellular targeting did not lead to clinical pulmonary compromise. The intravenous administration of SVF shou...

Safety of Technique and Procedure of Stromal Vascular Fraction Therapy: From Liposuction to Cell Administration

“…However, there was no clear explanation for the volume of saline solution or the time of infusion in this study [ 15 ]. In another phase I clinical trial, conducted by Comella et al, twelve patients with end-stage COPD were treated with one single SVF infusion [ 32 ]. The range of SVF dosing given to each patient varied from 150 to 300 million cells, in combination with 1000 mL saline solution.…”

“…We observed that a majority of these published studies used not more than 100 million SVFs, except one study which was done by Comella et al [ 32 ]. It is hypothesized that the fundamental reason for the use of this smaller amount of injected SVFs in clinical application is likely the inability of investigators to isolate large number of cells from adipose tissue collected from their patients.…”

First-in-man intravenous implantation of stromal vascular fraction in psoriasis: a case study

“… 13 This cluster of differentiation is part of the periendothelial network and is thought to be integral to the angiogenesis process. The use of SVF has been reported in a variety of indications including osteoarthritis, 14 – 16 degenerative disc disease, 17 sclerosis, 18 tendinopathy, 19 congestive heart failure, 20 chronic obstructive pulmonary disease, 21 radiation necrosis, 22 xerostomia, 23 and multiple sclerosis. 24 In addition, two studies have been published demonstrating the safety of SVF for a variety of indications used in a clinical outpatient setting.…”

Intra-Articular Implantation of Stromal Vascular Fraction Plus Platelet Rich Plasma in a Degenerative Meniscal Injury

“…Fat tissue can be easily and safely harvested and SVF can be collected bedside making it an attractive therapeutic option for physicians to offer to their patients [19]. A variety of publications have reported on the injection of SVF including: osteoarthritis [20, -21], degenerative disc disease [22], sclerosis [23], tendinopathy [24], congestive heart failure [25], chronic obstructive pulmonary disease (COPD) [26], radiation necrosis [27], xerostomia [28], psoriasis [29], and multiple sclerosis [30].…”