Adipose tissue contains adult mesenchymal stem cells that may modulate the metabolism when applied to other tissues. Stromal vascular fraction (SVF) can be isolated from adipose tissue mechanically and/or enzymatically. SVF was recently used to decrease the pain and improve the function of knee osteoarthritis (OA) patients. Primary and/or secondary OA causes inflammation and degeneration in joints, and regenerative approaches that may modify the natural course of the disease are limited. SVF may modulate inflammation and initiate regeneration in joint tissues by initiating a paracrine effect. Chemokines released from SVF may slow down degeneration and stimulate regeneration in joints. In this review, we overviewed articular joint cartilage structures and functions, OA, and macro-, micro-, and nano-fat isolation techniques. Mechanic and enzymatic SVF processing techniques were summarized. Clinical outcomes of adipose tissue derived tissue SVF (AD-tSVF) were evaluated. Medical devices that can mechanically isolate AD-tSVF were listed, and publications referring to such devices were summarized. Recent review manuscripts were also systematically evaluated and included. Transferring adipose tissues and cells has its roots in plastic, reconstructive, and aesthetic surgery. Micro- and nano-fat is also transferred to other organs and tissues to stimulate regeneration as it contains regenerative cells. Minimal manipulation of the adipose tissue is recently preferred to isolate the regenerative cells without disrupting them from their natural environment. The number of patients in the follow-up studies are recently increasing. The duration of follow up is also increasing with favorable outcomes from the short- to mid-term. There are however variations for mean age and the severity of knee OA patients between studies. Positive outcomes are related to the higher number of cells in the AD-tSVF. Repetition of injections and concomitant treatments such as combining the AD-tSVF with platelet rich plasma or hyaluronan are not solidified. Good results were obtained when combined with arthroscopic debridement and micro- or nano-fracture techniques for small-sized cartilage defects. The optimum pressure applied to the tissues and cells during filtration and purification of the AD-tSVF is not specified yet. Quantitative monitoring of articular joint cartilage regeneration by ultrasound, MR, and synovial fluid analysis as well as with second-look arthroscopy could improve our current knowledge on AD-tSVF treatment in knee OA. AD-tSVF isolation techniques and technologies have the potential to improve knee OA treatment. The duration of centrifugation, filtration, washing, and purification should however be standardized. Using gravity-only for isolation and filtration could be a reasonable approach to avoid possible complications of other methodologies.

/pdf/autologous-adipose-derived-tissue-stromal-vascular-fraction-2dkgdb6u.pdf

Autologous Adipose-Derived Tissue Stromal Vascular Fraction (AD-tSVF) for Knee Osteoarthritis

Knee osteoarthritis (OA) leads to significant pain and disability, prompting new cell-based injections to lessen the symptoms. Biological therapies such as autologous microfragmented adipose tissue (AMAT) and a stromal vascular fraction (SVF) are a common source for harvesting mesenchymal and progenitor cells. Platelet-rich plasma (PRP) is associated with cytokines and growth factors. Recent studies have reported good clinical outcomes with AMAT, SVF, and PRP in knee osteoarthritis treatment. However, the preparation, processing, and application technique are vital to achieving satisfactory results. Many studies have examined outcomes after AMAT, SVF, or PRP injection, with encouraging results. Still, there is a lack of studies describing a technique that combines both methods, the timing, and the amount of SVF or PRP injected. This technical note’s objective was to describe a standardized new technique composed of platelet and adipose stroma to treat knee osteoarthritis (OA) and the processing method.

Platelets and Adipose Stroma Combined for the Treatment of the Arthritic Knee

Enzymatically isolated stromal vascular fraction (SVF) has already shown to be effective as a treatment for osteoarthritis (OA). Yet, the use of enzymes for clinical purpose is highly regulated in many countries. Mechanical preparation of SVF results in a tissue-like SVF (tSVF) containing intact cell–cell connections including extracellular matrix (ECM) and is therefore less regulated. The purpose of this study was to investigate the immunomodulatory and pro-regenerative effect of tSVF on TNFα-stimulated chondrocytes in vitro. tSVF was mechanically derived using the Fractionation of Adipose Tissue (FAT) procedure. Characterization of tSVF was performed, e.g., cellular composition based on CD marker expression, colony forming unit and differentiation capacity after enzymatic dissociation (from heron referred to as tSVF-derived cells). Different co-cultures of tSVF-derived cells and TNFα-stimulated chondrocytes were analysed based on the production of sulphated glycosaminoglycans and the anti-inflammatory response of chondrocytes. Characterization of tSVF-derived cells mainly contained ASCs, endothelial cells, leukocytes and supra-adventitial cells. tSVF-derived cells were able to form colonies and differentiate into multiple cell lineages. Co-cultures with chondrocytes resulted in a shift of the ratio between tSVF cells: chondrocytes, in favor of chondrocytes alone (p < 0.05), and IL-1β and COX2 gene expression was upregulated in TNFα-treated chondrocytes. After treatment with (a conditioned medium of) tSVF-derived cells, IL-1β and COX2 gene expression was significantly reduced (p < 0.01). These results suggest mechanically derived tSVF stimulates chondrocyte proliferation while preserving the function of chondrocytes. Moreover, tSVF suppresses TNFα-stimulated chondrocyte inflammation in vitro. This pro-regenerative and anti-inflammatory effect shows the potential of tSVF as a treatment for osteoarthritis.

/pdf/mechanically-derived-tissue-stromal-vascular-fraction-acts-1bp4flo9.pdf

Mechanically Derived Tissue Stromal Vascular Fraction Acts Anti-inflammatory on TNF Alpha-Stimulated Chondrocytes In Vitro

. Authors' reply We thank Dr. Dart for supporting our research on the potential of autologous adipose- derived stromal vascular fraction (SVF) in combination with platelet- rich plasma (PRP) in the treatment of perianal Crohn's disease. 1 In our cohort study, we demonstrated the feasibil-ity and safety of SVF with PRP treatment as an add- on therapy to surgical procedures. 2 The rationale behind this therapy is based on the enhancement of local tissue regeneration. As Panes et al use ex vivo monoclonal expanded adipose- derived stromal cells (ADSCs), 3 it is proven that the regenerative properties are not unique to ADSCs, but are also found in the heterogeneous cell population of the lipoaspirate the ADSCs are derived from, such as SVF. 4 SVF with PRP offers the advantage of a direct, per- operative treatment mo-dality, without using any additives (mechanical fractionation instead of chemical or enzymatic fractionation). This makes it easy to use, has no challenging logistics and is cheap. 5 As like Alofisel, we demonstrated that repetitive use is possible and safe.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/apt.17415

Editorial: Heal thyself—Autologous therapy for perianal Crohn's disease. Authors' reply

(1) Background: osteoarthritis (OA) of the knee is a degenerative disease accompanied by pain, reduced mobility and subsequent decrease in quality of life. Many studies on OA of the knee have reported that using an intercellular acting-derivate like platelet-rich plasma (PRP) results in a limited effect or none at all. Authors hypothesized that adding tissue-Stromal Vascular Fraction (tSVF) to PRP (Platelet Rich Stroma (PRS)) would reduce pain and improve functionality in osteoarthritis of the knee. (2) Methods: a consecutive case series of fifteen patients (aged 43–75 years) suffering from OA of the knee (Kellgren–Lawrence stage two to three) were treated with a single injection of autologous PRS. tSVF was mechanically isolated by means of the fractionation of adipose tissue (FAT) procedure. Clinical evaluation was done using a visual analogue score (VAS) score, an adapted Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and Lysholm score at fixed time points: pre-injection as well as three, six and twelve months post injection. (3) Results: VAS and WOMAC scores improved significantly after twelve months (p 0.05) in comparison to pre-injection measurements. No complications were seen in any of the patients. One patient was excluded due to a total knee arthroplasty. (4) Conclusions: a single injection with PRS for OA of the knee seems to lead to an improvement of function and simultaneous reduction of pain and joint stiffness for a period of twelve months. Further controlled trials are required to determine the optimal treatment regimen and evaluate long-term results.

https://www.mdpi.com/2076-3417/10/14/4691/pdf

Robbert van Dijck

Papers

Platelet Rich STROMA, the Combination of PRP and tSVF and Its Potential Effect on Osteoarthritis of the Knee