A Retrospective Study of Stromal Vascular Fraction Cell Therapy for Osteoarthritis

Abstract

Introduction

Osteoarthritis (OA) is the common cause of pain and disability in adult individuals. It is characterized by degeneration of articular cartilage, inflammation of the synovium tissue, and tendon [1, 2]. Pathogenesis of OA involves multiple factors, including age, joint trauma, genetic factors, altered biomechanics, and obesity [3]. Knee OA-associated pain is well-recognized as typically transitioning from intermittent weight-bearing pain to a more persistent, chronic pain [4]. Fatigue, sleep trouble, psychological stress, poorer perceived health, reduced activity, function decline, disability, and reduced independence are consequences of knee OA-associated pain [5]. An increase in C-reactive protein (CRP) level was associated with the presence and progression of knee OA, particularly with synovial fluid interleukin 6 (IL-6) and degree of synovial fluid infiltration, symptoms of pain, and stiffness [6]. Cartilage destruction is the result of molecular damage and inability to effectively manage mechanical forces, leading to the production of a host of inflammatory mediators, which include cytokines and chemokines [7]. Early OA is characterized by increased mononuclear cell infiltration and overexpression of inflammatory mediators compared with a late disease [8]. Treatment options targeting inflammatory processes in this stage might be most productive for the prevention and therapy of OA [3]. Current therapeutic strategies for OA include drugs for control of pain and inflammation, such as nonsteroidal anti-inflammatory drugs, analgesics, locally administered corticosteroids, and viscosupplementation [9]. Tectorigenin has a positive role in OA restriction because of its anti-inflammatory and antioxidant activities. Wang et al demonstrated the chondroprotective potential of tectorigenin in the OA process and prevention of articular cartilage degeneration and chondrocyte apoptosis via the NF-κB P65 pathway [9]. Stem cell therapy is a developing therapeutic modality in the treatment of OA. Adipose tissue-derived stromal vascular fraction (SVF) contains a variety of cells, including mesenchymal stem cells (MSCs), which is a promising therapeutic option for OA. With the application of conventional liposuction and isolation methods, SVF in adipose and connective tissues can be easily obtained from patients [10]. Michalek et al showed significant improvement in OA symptoms, particularly pain reduction and decrease in nonsteroidal anti-inflammatory drug usage in a large group of 1,128 patients with OA [11]. Numerous clinical studies have been published about OA treatment with autologous adipose SVF. However, a limited number of clinical studies include a large group of subjects. Efficacy assessments mostly include evaluation of pain, joint movement, joint stiffness, and nonsteroidal anti-inflammatory drug usage in the general group of OA patients. In the present retrospective chart review study, we analyzed not only changes in pain and mobility parameters but also the correlation of improved parameters with the arthritis stage in a group of 350 subjects with OA.

Materials and Methods

Results

No complications associated with the processing of adipose tissue or preparation of SVF cells were noticed. Follow-up examination of subjects 7 days, 3, 6, and 12 months after SVF therapy showed that subjects did not experience adverse reactions connected to treatment, further demonstrating the safety of SVF therapy.

Pain and mobility assessments were conducted 7 days, 3, 6, and 12 months after SVF cell therapy. Seven days after treatment, 45.2% of subjects experienced improved pain levels. Three, 6, and 12 months after treatment, the number of subjects with improvement in pain levels reached 75.3%, 84.4%, and 84.9% correspondingly (Table 1). A statistically significant improvement in subjects’ pain levels was observed 3, 6, and 12 months compared to 7 days after treatment (P < 0.05). No statistically significant difference was observed in the subjects’ pain levels between 3-, 6- and 12-month post-therapy time.

Improvement in mobility was in 45.2% of subjects 7 days after therapy. The subjects’ number with improvement in mobility reached 75.2% 3 months, 84.4% 6 months, and 84.9% 12 months after treatment (Table 2). Improvement in subjects’ mobility was statistically significant 3, 6, and 12 months compared to 7 days after treatment (P < 0.05). The difference in subjects’ mobility between 3-, 6- and 12-month post-therapy period was not significant.

After adipose tissue-derived SVF cell therapy, the better outcome was observed in subjects with arthritis stage III compared to arthritis stages I, II, and IV. Improvement in pain levels and mobility was observed in 52.6% of subjects with arthritis stage III (Table 3).

The number of overweight and obese patients with arthritis stages III – IV and IV were statistically different from the underweight and normal weight having patients (P < 0.001). The small number of patients in the smoking and alcohol-consuming groups did not allow to do a statistical correlation of these factors with arthritis stages III – IV and IV. One hundred ninety-five subjects did not experience improvement in pain levels after SVF therapy. Among them, 43 subjects (47.8% from the general number of 90 subjects with pre-existing conditions) had pre-existing conditions. Statistical analysis showed that a high percentage of patients with pre-existing conditions in the group of patients who did not experience improvement in pain levels are not random (P < 0.001). Statistical analysis did not reveal the impact of pre-existing conditions on the improvement of mobility after SVF therapy. Because most subjects were overweight (294 subjects, 84.0%), the statistical correlation of SVF treatment efficacy to the BMI was not revealed. There was no statistically significant impact of smoking and alcohol consumption on the efficacy of SVF treatment.

Discussion

In the present study, we reported the safety and efficacy of adipose tissue-derived SVF cell therapy in 350 subjects with hip and knee OA.

OA is a multifactorial disease characterized by changes in the structure and function of the whole joint. Mechanical factors have a central role in this multifactorial process [12–14]. The most commonly used existing treatments for OA (such as nonsteroidal anti-inflammatory drugs, cyclo-oxygenase-2 inhibitors, and total joint replacement) are causing adverse events compared with conservative interventions such as exercise, weight loss, braces, and orthotics [15]. To date, there is no cure from OA, and current therapeutic strategies are primarily aimed at reducing pain and improving joint function. Cell-based therapy is a new investigational approach that holds promise to enhance recovery from OA [16]. SVF cell therapy for OA is a rapid, effective, and safe method that significantly improves the quality of life in patients with OA [17]. The cell types found in the SVF include preadipocytes, fibroblasts, adult mesenchymal stem cells, monocytes, macrophages, lymphocytes, as well as pericytes related to angiogenesis [18]. Mesenchymal stem cells can migrate to sites of injury, inhibit pro-inflammatory pathways, and promote tissue repair through the release of anabolic cytokines and direct differentiation into an array of specialized connective tissue cells [19]. Autologous blood products such as platelet-rich plasma act as an adjuvant of surgical treatment and its intra-articular delivery showed beneficial effects for OA treatment [20]. In our study, to maximize the therapeutic effect, SVF cells were combined with platelet-rich plasma and administered via intraarticular injection.

Published clinical studies have mostly analyzed the efficacy of SVF cell therapy on a small number of patients. Also, these studies do not describe the correlation of improved symptoms with the arthritis stage. In the current retrospective chart review study, we analyzed the effect of SVF cell therapy on the improvement of pain levels and mobility in 350 subjects with OA. The results of the study are concordant with several previous clinical studies [20–22]. Furthermore, for the first time, the results of the current study indicate that autologous SVF cell therapy is more effective in subjects with arthritis stage III. The limitations of this study are retrospective nature and the lack of a placebo group. The efficacy of SVF cell therapy for OA needs to be confirmed by further controlled long-termed studies.

In conclusion, our study of 350 subjects with hip and knee OA demonstrated a significant improvement in pain levels and mobility 3, 6, and 12 months compared to 7 days after autologous SVF cell therapy. Cell therapy demonstrated a strong safety profile with no severe adverse events or complications reported. Subjects with arthritis stage III showed better outcomes after SVF cell therapy, compared to arthritis stages I, II, and IV. Autologous SVF therapy is a rapid, effective, and safe method that significantly improves the quality of life in patients with OA.

Acknowledgments

References