Evaluation of Clinical Efficacy of Autologous Adipose Tissue Derived ADSCSs in Treatment of Osteoarthritis (OA)
Condition: Osteoarthritis, Knee
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Osteoarthritis (OA) is a degenerative disease of great morbidity in which therapies are
      typically palliative and only alleviate pain Mesenchymal stem cells ,adipose derived stromal
      cell are possible new chondroprotective regenerative treatment modalities.

      Clinical Effectiveness after administration of adipose derived stromal cells along with
      platelet rich plasma was investigated in 140 patients having moderate to severe knee (stage 3
      and 4)

      Patients were evaluated and followed up for 2 year by subjective WOMAC score,six minute
      walking distance ,need of rescue medication Radiographic and MRI evaluation of joint space
      and cartilage thickness respectively
    

Detailed description: 
      Osteoarthritis (OA) is a degenerative disease that affects the articular cartilage over time
      and is accompanied by alterations to the synovium, subchondral bone, ligaments, and menisci,
      as well as hypertrophy of the joint capsule.

      Therapies are typically palliative and only alleviate pain in a symptomatic way, failing to
      stop cartilage degeneration and the following breakdown of other joint structures Therefore,
      it is crucial for researchers to tackle the challenge of creating OA-modifying therapeutics.
      The potential of adult mesenchymal stem cells (MSCs) and adipose derived stromal cells
      fraction also known as stromal vascular fraction has recently being evaluated for
      chondroprotective efficacy in oa knees.

      The present study was taken to evaluate Clinical Effectiveness without any doubt after
      administration of Non enzymatically processed adipose derived stromal cells along with
      platelet rich plasma in large number (140 patients) having moderate to severe knee (stage 3
      and 4) with objective MRI assessment and 2 year follow up.

      Methods

      The selection criteria included patients 50 years of age or older with symptomatic primary
      osteoarthritis of the knee that was defined by daily pain for the previous three months,
      analgesic use at least once per week, less than 30 minutes of morning stiffness, and a WOMAC
      score of 75 in the target knee. Grades 3 and 4 kellergen Radiographic Grading Scale of
      Osteoarthritis were part of the radiographic qualifying requirements. The exclusion criteria
      included individuals with clinically significant systemic diseases and patients with evidence
      of secondary knee osteoarthritis or severe osteoarthritis (joint space width-JSW 2 mm).

      The WOMAC score, developed by Western Ontario and McMaster Universities, is a commonly used
      indicator of patients' subjective ratings of pain, joint mobility, and physical impairment.
      With 5, 2, and 17 questions, respectively, it assesses three dimensions: pain, stiffness, and
      physical function. A minimum score is 0, highest score is 96. The maximum score for each
      subscale is 20, 8, or 68, correspondingly .

      In order to measure the six-minute walking distance (6MWD), a 50 m distance was marked in an
      internal hallway, and participants were instructed to walk as far and as rapidly as they
      could during the course of six minutes. The whole distance was calculated and noted.

      Using previously described procedures, antero-posterior radiographs of the knee joints were
      taken with patients standing at a distance of 1 m from the X-Ray source, with the knee
      completely extended. The joint space width was measured at its narrowest point (minimal JSW).
      According to a prior publication this trend was indicated by a JSW loss of more than 0.50 mm
      over the trial.

      Antero-posterior radiographs of the knee joints were acquired using the previously described
      techniques while patients stood 1 m away from the X-Ray source with their knees fully
      extended. At the joint space's narrowest point, the breadth was measured (minimal JSW). This
      tendency was shown by a JSW loss of more than 0.50 mm during the study, in accordance with a
      previous publication.

      Patients were instructed to take etoricoxib at a dose of no more than 90 mg BD after meals if
      their discomfort was intolerable. They were instructed to take 30 mg of codeine as needed if
      the discomfort persisted and to report the next day. Aside from any symptoms or indications
      that the patient reported, laboratory-based hematological and biochemical tests were also
      performed as part of the tolerance and safety evaluations.

      A microscopic examination of the synovial fluid was performed at baseline and two years after
      the surgery to check for abnormal cell counts. According to the degree to which they
      interfered with the subject's everyday activities, adverse occurrences were classified as
      isolated, intermittent, or chronic. The possible causal association between the supplement
      and the outcome was categorized as Definite/Possible/Probable/Non-Assessable/None. The
      institutional committee for stem cell research and therapy gave its approval to the project.
      All of the patients provided written consent to participate in the trial after receiving
      enough information.

      SVF preparation :

      With the help of a 3 mm aspiration cannula and tumescent solution, about 100 ml of fat was
      collected from each patient's belly and put into sterile, disposable 250 ml conical
      centrifuge tubes. The adipose tissue underwent two PBS washes before being sonically
      cavitated by ultrasound at 10 mega hertz ,50 W for 30 minutes with 5-minute intervals of
      agitation. The SVF was then extracted as a pellet by dividing the suspension into four 50 ml
      centrifuge tubes and centrifuging them at 500 g for five minutes. To get rid of any remaining
      enzyme, the pellet was washed twice with regular saline before being resuspended in PBS. The
      SVF suspension was spun at 500 g for 5 min after being filtered using a 100 m cell strainer.
      The extra fluid was dumped. The pellet was put back together with regular saline and passed
      through a 40 m cell strainer. Samples were collected in order to count the number of cells,
      assess their vitality, and cultivate, and define the stem cells.

      PRP preparation: The same donor who provided the adipose tissue's peripheral blood also
      provided the platelet-rich plasma. ACD Solution A was added to BD yellow top vacuum tubes
      with 20 ml of peripheral blood, and the tubes were centrifuged at 800 g for 10 min. To obtain
      a platelet pellet, the plasma fraction was collected and centrifuged at 1000 g for 5 min.
      After that, just 3 ml of plasma remained, which was used to resuspend the platelets.
    

Intervention name(s): Autologous adipose tissue derived stromal cells
Intervention type(s): Biological
Intervention description(s): autologous adipose tissue derived stromal cells is recovered as pellet after non enzymatic processing with sonication using ultrasound . This isolation process yielded an abundant population of Adipose stromal cells(ASCs) which have multipotent differentiation potential. Immunophenotype is a CD14-, CD29+, CD31-, CD34low/+, CD45-, CD73+ and CD105+ , the SVF represents the 50-70% in volume of a lipoaspirate specimen. The SVF hosts a heterogeneous cell population (110x103 cells/ml on average) comprising mainly CD105+ mesenchymal stem cells (MSC,2-- 20%), plus a wide number of CD34+ hematopoietic cells (40%)
Intervention model: Single Group Assignment
Intervention model description: This is prospective, open label, single arm clinical study that will establish the safety and efficacy of adipose derived stromal cells in patients with osteoarthritis disease. Total 140 subjects were enrolled in the study. Each subject will receive intra-articular Autologous ADSC with PRP along with standard treatment for osteoarthritis disease.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: : stromal vascular fraction (SVF), adipose derived stromal cells, adipose tissue, connective tissue, osteoarthritis, therapy