Treatment of Osteoarthritis With the Stromal Vascular Fraction of Abdominal Adipose Tissue - a Pilot Study
Condition: Osteoarthritis; Stem Cells
MeSH terms: Osteoarthritis
Study type: Interventional

Summary: 
      To investigate the feasibility and short term safety issues of treatment of knee
      osteoarthritis with intra-articular injection with the stromal vascular fraction of abdominal
      adipose tissue (SVF) harvested and prepared using the Lipogems System.

      Hereby we wish to pave the road for a high quality randomized controlled trial investigating
      effectiveness of treatment of knee osteoarthritis with SVF looking at patient reported
      outcome, function, homeostasis of the joint and cartilage regeneration.
    

Detailed description: 
      Background Osteoarthritis (OA) of the knee is a destructive joint disease, causing
      degeneration of cartilage, damage to the underlying bone and morphological changes to the
      joint1. It is a major public health concern due to the increased life expectancy of the
      ageing population2,3. No approved medical treatment that reverses the morphological changes
      currently exists. Conventional treatment includes physiotherapy, pain killers, braces and in
      end-stage OA surgical knee replacement4.

      Treatment of Osteoarthritis with Paqe 3 Version 2 the Stromal Vascular Fraction of Adipose
      tissue 02-11-2015 During the past decade researchers have started to explore the regenerative
      potential of mesenchymal stem cells (MSC) in OA5. MSCs are multipotent progenitor cells able
      to give rise to osteocytes, adipocytes, chondrocytes, myoblasts and tenocytes6. MSCs were
      first used to treat Chondral defects in 19987 and to treat OA in 20028. Since, a number of
      case reports and prospective series have been published showing significant short term and
      long term effect on pain and cartilage thickness5. Recently a prospective case-series of 1128
      patients involving 1856 joints were treated with the stromal vascular fraction of abdominal
      Adipose tissue (SVF) which is a rich source of mesenchymal stem cells. 86% of the treated
      patients showed an improvement of at least 50% in modified Knee/Hip Osteoarthritis Outcome
      Score (KOOS/HOOS) at 3 months and 129. Only 0.9% of patients were non-responders showing no
      improvement after treatment. No serious adverse effects like infection or tumor formation
      were observed9, which is in accordance with previous studies10. Non-manipulated or minimally
      manipulated cell therapies have been used within a wide range of medical conditions
      including: stroke, myocardial infarction, Crohn's disease, rheumatoid arthritis and breast
      augmentation. More than 17,000 scientific articles have been published reporting treatment of
      more than 320,000 patients11. No severe safety issues have been raised12.

      Mesenchymal stem cells can be derived from bone marrow or adipose tissue5. Most research has
      been performed on bone marrow-derived stem cells but the past years a series of studies have
      been published showing promising effect of Adipose-derived mesenchymal stem cells (AMSCs). By
      using AMSC a large amount of cells can be harvested from a small volume of tissue thereby
      avoiding the costly and time consuming process of expanding the cells in culture5,9.
      Abdominal adipose tissue has been shown to have a 1000 times higher concentration of AMSC
      than other investigated adipose tissue9. This opens for the possibility of a one-step
      procedure where cells are harvested and injected during one visit in the outpatient clinic.
      The optimal dose of AMSC is unknown but the effect seems to be dose-dependent with doses
      around 1.0 x 108 AMSCs per injection being desirable5,9. The stromal vascular fraction of
      abdominal Adipose tissue is a rich source of adipose derived mesenchymal stem cells.

      In 2014 the Lipogems system has been launched as a commercial of-the-shelf product:
      http://lipogems.eu/. The Lipogems system is an enzyme-free technology developed to process
      lipoaspirates in a closed system, resulting in a non-expanded adipose tissue product that
      contains SVF13. Before using this product in larger scale a controlled study of its
      feasibility and safety is needed.

      Study Objective To investigate the feasibility and short term safety issues of treatment of
      knee osteoarthritis with intra-articular injection with the stromal vascular fraction of
      abdominal adipose tissue (SVF) harvested and prepared using the Lipogems System.

      Hereby we wish to pave the road for a high quality randomized controlled trial investigating
      effectiveness of treatment of knee osteoarthritis with SVF looking at patient reported
      outcome, function, homeostasis of the joint and cartilage regeneration.

      6 Treatment Patients participating in the study are treated according to the Danish National
      Clinical Guidelines for people with osteoarthritis16. They receive three months of
      physiotherapy, are guided concerning the optimal pharmaceutical treatment with painkillers
      and people with BMI above 28 are offered a consultation with a dietitian.

      6.1 Description of the active treatment The active treatment is an intra-articular injection
      with the stromal vascular fraction (SVF) harvested from the patient's own abdominal
      subcutaneous fatty tissue. SVF is harvested using the Lipogems system.

      6.1.1 Harvest of SVF Harvest of SVF is done under sterile conditions in the outpatient
      clinic. The patient is positioned supine on an examination bench. The area from which the
      tissue will be harvested is marked on the skin with a surgical marker. The area is app. 8cm
      (cranio-caudal) x 20cm (lateral) and situated just below the umbilicus. Local anesthesia is
      applied to the whole area with a suspension of Carbocain 1%, 200ml isotonic saline,
      adrenaline and 10mmol Bicarbonate. Surgical cleaning is performed twice and a sterile draping
      is applied. Through a stab incision the harvesting needle is introduced to the subcutaneous
      fat and suction is applied. 20ml to 40ml of subcutaneous adipose tissue is harvested. At the
      end of the procedure the skin is closed with a plaster.

      6.1.2 Preparation of SVF for implantation The syringes with subcutaneous aspirate are
      prepared using the Lipogems system. The Lipogems system is an enzyme-free technology
      developed to process variable amounts of lipoaspirates in a closed system, resulting in a
      nonexpanded adipose tissue product that contains SVF. The technology works through a mild
      mechanical tissue cluster size reduction. Thereby avoiding the use of any enzyme and
      additional processing (i.e., centrifugation and subfractional harvesting).13 6.1.3
      Implantation of SVF Implantation of the SVF is done under sterile conditions in the
      outpatient clinic. The patient is positioned supine on an examination bench with the affected
      knee stretched. The superior pole of the patella is palpated and the femoral condyle is
      marked with a surgical marker. The suprapattelar recess is located by ultrasound, local
      anesthesia is applied to the injection site and surgical cleaning is performed twice.
      Injection of the SVF in to the suprapattelar recess is done using a 21 gauge syringe under
      direct visualization by ultrasound. At the end of the procedure the skin is closed with a
      plaster.

      6.1.4 Control of dose of injected SVF Control of the dose of AMSC in the injected SVF is
      performed after injection. As a consequence of the logistical favorable setup where harvest
      and implantation is performed in a one-step procedure it is not possible to count the AMSC
      before injection. Instead one mL of the solution is sent for cell count in the pathological
      department.
    

Intervention name(s): injection with the stromal vascular fraction (SVF) of adipose tissue
Intervention type(s): Biological
Intervention description(s): Description of the active treatment The active treatment is an intra-articular injection with the stromal vascular fraction (SVF) harvested from the patient's own abdominal subcutaneous fatty tissue. SVF is harvested using the Lipogems system.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment