## 1 Introduction  
Osteoarthritis (OA) of the knee is a chronic inflammatory disease that results in degeneration of cartilage in the joint, often accompanied by persistent pain, joint deformities and stiffness [1]. Combinations of these symptoms can lead to reduced mobility and a decreased quality of life [1, 2]. The lifetime risk to develop symptomatic knee OA is 45% at the age of 85 years and is expected to increase because of increased obesity and aging in the Western World population [3]. In 2011, OA was the second most expensive condition treated in American hospitals, accompanied by a total cost of almost $15 billion dollars per year [4]. In 50% of the cases, total knee arthroplasty was the reason for hospitalization [5]. The total cost related to the treatment OA is presumed to increase even more. This would be mostly due to the fact that the number of knee replacements is expected to increase by 673% in the USA by the year 2030 [6, 7]. To date, most available treatments to decrease symptoms and the progressive character of OA are pharmacological and surgical treatments, e.g., anti-inflammatory or analgesic medication and joint replacement [8; 9]. Ultimately, arthroplasty of the knee is the only available treatment resulting in a significantly improved mobility and reduction of pain, despite the risk for new postoperative sequelae (e.g., problems with kneeling, persistent pain and pain during walking) [10]. Arthplasties are expensive and are associated with a long recovery period. [PERSON] et al. found a return to work after total knee arthroplasty (TKA) of 12 weeks [11]. Multiple studies have been published focusing on new low-cost, regenerative and pain reducing therapies with a quick recovery time, e.g., autologous substrates, such as platelet rich plasma (PRP) or stromal vascular fraction (SVF) [8; 9; 12]. PRP can be easily obtained from whole centrifuged blood and is defined as a portion of plasma fraction of autologous blood that preferably has a 2 to 2.5 increase of platelet concentrations above baseline [9]. Platelets contain numerous different growth factors, e.g., insulin-like growth factor (IGF), transforming growth factor \(\beta\)1 (TGF-\(\beta\)1) and vascular endothelial growth factor (VEGF) [9]. These growth factors increase proliferation, migration, differentiation and angiogenesis of adipose derived mesenchymal or stromal cells (ASCs) [13; 14]. ASCs are multipotent stromal cells that reside in SVF of adipose tissue as precursor cells (supra-adventitial cells and pericytes) and possess regenerative capacities [15; 16]. SVF consists of many other non-adipocyte cell types as well e.g., fibroblasts, lymphocytes, periodontitis cells and endothelial cells [12]. SVF can be isolated enzymatically or non-enzymatically from adipose tissue [17]. Enzymatic isolation of SVF results in a single cell suspension without cell-to-cell nor cell-to-extracellular matrix-communications (ECM), the so-called cellular SVF (cSVF) [17; 18]. In contrast, non-enzymatic or mechanical isolation of SVF results in a tissue-like SVF (tSVF) mainly depleted of adipocytes, while other cell types as well as ECM remain mostly preserved [17; 18]. Administration of mechanically isolated tSVF is less time-consuming as well as less expensive than enzymatic isolated cSVF [17]. The combination of the multiple growth factors and cells in tSVF stimulate angiogenesis, promote proliferation of parenchymal cells, suppress apoptosis and modulate immune responses [17]. Furthermore, the extracellular matrix acts as a scaffold ensuring slow release of growth factors and probably increases cell survival [19]. Thus, tSVF is anticipated to regenerate damaged tissue and/or modulate inflammation. These two processes stand at the very base of OA. It was hypothesized that combining PRP and mechanically dissociated lipoaspartate tSVF (Platelet Rich Stroma (PRS)) would lead to a more effective treatment of OA of the knee.