The publication discussed below is a simplified/re-organized version of the original article.  This study is utilizing the Macquarie Stem Cells method of cell separation.
It has been published in the Journal Of Evidence Based Medicine & Healthcare.
Full article can reference can be found on the bottom of this page.

USE OF AUTOLOGOUS ADIPOSE TISSUE DERIVED STROMAL VASCULAR FRACTION IN TREATMENT OF KNEE OSTEOARTHRITIS AND CHONDRAL LESIONS

Vinay Tantuway1, S. A. Mustafa Johar2, Murtza Rassiwala3, Chhavi Jain (MPT)4, Neethu Shaji5, Farida Bandookwala6

Study Introduction

STATEMENT OF THE PROBLEM:
An experimental study to assess the effectiveness of autologous adipose tissue derived stromal vascular fraction in treatment of knee osteoarthritis and chondral lesions. To observe the Safety and Efficacy of Autologous Stromal Vascular Fraction on Pain and Inflammation associated with Osteoarthritis of the Knee Joint.

OBJECTIVES:

  1. To find out the safety & efficacy of the autologous adipose derived stromal vascular fraction in the treatment of osteoarthritis.
  2. To find out the role of autologous adipose derived stromal vascular fraction in the treatment of osteoarthritis.
  3. To evaluate the difference in KOOS score of patients before and after SVF treatment.
  4. To find out the correlation between BMI of the patient and post-operative KOOS score.

OPERATIONAL DEFINITIONS: SVF:
Stromal vascular fraction derived from autologous adipose tissue extracted from mini-liposuction under tumescent anaesthesia. In the vast majority of scientific publications only the term adipose tissue is used, but the true source of SVF cells is not the adipose part but only the stromal (i.e. loose connective tissue) part of the fat obtained typically by liposuction.

SVF contains a large cellular mix inclusive of;

  • pericytes
  • adipocytes
  • fibroblasts
  • endothelial cells
  • vascular progenitorts
  • supra adventicial cells
  • mesencymal stem cells
  • haematopoietic stem cells
  • endothelial progenitor cells
  • haematopoietic progenitors

DEFINITION OF KOOS Score:
(Knee Injury & Osteoarthitis Outcome score) scoring system was used to assess the outcome. The KOOS is a knee-specific instrument, developed to assess the patients’ opinion about their knee and associated problems. The KOOS evaluates both short-term and long-term consequences of knee injury. It holds 42 items in 5 separately scored subscales; Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Rec- reation (Sport/Rec), and knee-related Quality of Life (QOL).(21)

The Demographic & Selection for Treatment

INTRODUCTION TO THE PATIENT DEMOGRAPHIC
We have given SVF injection to 31 patients from May 2015 to July 2015, in 62 joints. Most of the patients were in age group 41-60 yrs. i.e. 19 out of 31 (Range 26yrs to 78 yrs.). As per sex distribution there was 23 female and 8 male in study. We studied 19 patients 38 joints were injected with SVF with minimal follow-up of 6wks in detail and we are able to demonstrate safety with no serious side effects reported in 6 week of follow-up and clinical improvement in a vast majority of patients. Some patient’s experienced local pain and swelling at the injection site, but those symptoms were lasting shortly and were well controlled with common analgesics.

BMI ranges from 21.5 to 37 in 19 patients. 5 patients (26.3 %) had associated cardiovascular disease, 1 patient (5.3%) had migraine and one patient (5.3%) had undergone unicompartment knee arthroplasty but majority 12 patients (63.2%) patients had no associated disease. One Patient had grade II, 12 patients had grade III & 6 patients had grade IV osteoarthritis (as per Kellgren-Lawrence classification).

MATERIAL & METHODS: A prospective experimental research design is adopted in this study 31 patients were included in the study that had osteoarthritis. All the patients underwent SVF therapy. Out of which 19 patients were followed for their improvement in KOOS scores after 1, 4 and 6 weeks of surgery. Some patients suffered OA in joints other than the knees, the KOOS questionnaire is designed to follow up only the knee joints therefore this is a contributing factor to the loss of follow up. Further study will be done with more number of patients with longer follow-up.

SAMPLE SELECTION CRITERIA:

Inclusion Criteria:

  • Patients with indication of Osteoarthritis, grade 2 or more (Kellgren-Lawrence) which can be caused due to general degeneration or chronic injury.
  • Patients range from 18-90 years of age.
  • Patients must be able to comply with treatment plan, laboratory tests and periodic interviews.
  • Patients with adequate renal function, Creatinine ≤ 1.5 mg/dl.
  • Patients with adequate cardiac and respiratory function.
  • Patients with adequate blood coagulation activity, PT(INR) < 1.5, APTT.
  • Patients must have adequate immune system function, with no known immunodeficiency disease.
  • Greater than 6 months knee pain on the index side (left or right knee).

Exclusion Criteria:

  • Neoplastic cancer within 5 years prior to screening, except for cutaneous basal cell or squamous cell cancer resolved by excision.
  • Presence of clinically significant acute or unstable cardiovascular and cerebrovascular (stroke).
  • Diagnosis of a transient ischemic attack in the 6 months prior to screening. Patients infected with hepatitis B, C or HIV. Patients with Body Mass Index (BMI) > 40kg/m2. Presence of active infection.
  • Pregnancy & lactation. Any other illness, psychiatric disorder, alcohol or chemical dependence that in the opinion of the investigator would render a patient unsuitable to participate in the study.
  • Conditions/therapies/factors which could confound or interfere with the evaluation of pain/mobility including, but not limited to: Knee instability, any varus/valgus deformity of more than 10º, a deformity requiring osteotomy or complex surgery.
  • Gout or pseudo gout.
  • Treatments with strong opioid drugs in the previous 4 weeks for other pain rather than knee osteoarthritis.
  • Corticosteroid injection at treatment site within 1 month.
  • Consistent use of NSAIDs within 48 hours of procedure.
  • Health condition (including known allergy to local anesthetic drug) that does not allow to perform liposuction in local anesthesia.

 

Reporting of Patient Demographic

age BMI grade tables

Procedure Walk Through

Patient Consent:

  • Discussion and signing of consent forms: Risks, benefits and alternatives of treatment are discussed. Patient understands that the proposed therapy is not intended to cure any disease. Patient understands that the intended therapy might have no utility at all and is willing to take the risks of no benefit whatsoever.
  • The patient understands that he/she is consenting to participate in a study and although agreeing to return to the clinic at designated intervals for follow-up visits, and to respond to the questionnaires, there is no obligation on their part to do so and participation is voluntary.

Lipo aspiration (Performed by surgeon on staff):

  • Patient prepped in a sterile manner.
  • Pre-procedural antibiotics, anxiolytic and/or opiate pain medication administration if necessary.
  • Stab incisions are made for cannula entry with #11 blade after local infiltration with 1% Lidocaine with epinephrine 1:100, 000.
  • Areas to be treated are then infiltrated with the tumescent anesthesia fluid with the following concentration of Lidocaine and epinephrine using the infiltration cannula. (40 ml of Lidocaine 2% without epinephrine plus 1 ml of epinephrine 1% are added to a 1000 ml bag of 0.9% Normal Saline.)
  • 300 – 450cc adipose tissue is aspirated into a sterile container containing sterile 0.9% Normal Saline and sodium bicarbonate.

Cell Seperation Prior to Injection

  • Take patients adipose (fat) that was harvested to lab area.
  • Prepare the Bio Hood Class II & take sample then divide into 50ml tubes.
  • The fat is processed in ACRU. Ultrasonic cavitation is used to separate fat and stromal vascular fraction.
  • Then 50ml tubes are centrifuged.
  • Separate & remove the pellet in the bottom of tube away with best of care not to disturb the pellet.
  • Filter the cellular mix.
  • Perform a cell count and viability test using the Muse cell flow cytometer.

Injection Method – Intra-Articular

  • If the patient has osteoarthritis in both knees then both knees will be injected, with the worst knee identified as the Index knee, which will be reported on.
  • Area is prepared for injection with Chlorhexidine.
  • Local anesthetic (Lidocaine 1%) given to skin and deep tissue as needed.
  • SVF are injected ultrasound guidance to improve the accuracy of the injection/treatment.

Patient Follow Up:

  • Patient is discharged when stable after observation and all post procedure instructions have been discussed.
  • Patient is asked to report any side effects such as fever, pain and others.
  • Patient is seen for follow up next day or within one week.
  • Patients are interviewed by phone, email, or in person and asked to complete the KOOS questionnaires prior to initial treatment, at 1 week, 1 month and at 6 weeks.

The Statistical Hypothesis for Final Data Analysis

Hypothesis 1(H1): There is a significant improvement on the pre and post op KOOS score in patients who underwent Autologous adipose derived stromal vascular fraction injection in the treatment of osteoarthritis.

Hypothesis 2 (H2): There is significant correlation between BMI of the patients and their post-operative KOOS score after Autologous adipose derived stromal vascular fraction injection in the treatment of osteoarthritis.

A significance value of P ≤0.05 is used throughout the study to confirm the hypothesis.

DATA ANALYSIS AND INTERPRETATION:
Parametric test is used to find the difference in KOOS scores of 19 patients for various subscale, prior to the surgery, one week after the surgery and 6 weeks after the surgery.

Paired t test was used to find out the difference in pre and post score of patients who underwent SVF therapy.
The intervals were;

  1. Before the treatment
  2. 1 week after the treatment and
  3. 6 weeks after the treatment

A statistical significance is assessed for difference in the scores were found between the scores of Pain, Symptoms, Activity of Living (AoL), Quality of Life (QoL), average score, before surgery and after one and 6 weeks of surgery. Karl Pearson correlation is used to test the correlation between BMI, grade of Osteoarthritis and different scores of patients after 6 weeks of surgery.

SPSS version 20 was used to do the statistical analysis of the study.

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The above table signifies that t test shows extremely significant improvement in KOOS score for Pain (t=-10.926), symptom (t=-5.418), AoL (t=-11.195), QoL (t=-6.633) and average (t=-11.323) when pre-operative & 1 week scores were compared at the level of p ≤ 0.05 (df=18). There is also extremely significant improvement in KOOS scores for Pain (t=-9.545), symptom (t=-4.313), AoL (t=-14.457), QoL (t=-6.274) and average (t=-11.799). When pre-operative & 6 week scores were compared at the level of p ≤ 0.05 (df=18). When scores of 1 week post-op are compared with 6 week post-op there was no significance difference was found in average KOOS, KOOS pain, KOOS symptom & KOOS QoL but there was significant improvement in KOOS AOL (t=), P <0.05.

comparison BMI

A positive correlation was found in BMI and average KOOS (r=0.411), KOOS Pain (r=0.492), KOOS symptom (r=0.133), KOOS AoL (r=0.319) and KOOS Qol (0.164) in patients who underwent SVF therapy. A negative correlation was seen between grade of OA and KOOS score improvement in patients who underwent SVF therapy.

FINAL CONCLUSIONS

A total of 31 patients were treated with a combining 61 joints inclusive of the knee and hip joints.

Several patients suffered comorbidities other than osteoarthritis such as cardiovascular disease, migraine and rheumatoid arthritis prior to having the treatment. These co-morbidities were not followed up to assess the response of the disease when the patient was injected with the SVF.

The minimum follow up period was 6 weeks.

All of the patients whom had been treated (100%) responded to the SVF and showed improvements.

The grades of arthritis which responded were between grades 2, 3 & 4. There were slower improvements noted in patients KOOS scores if the patient had a higher grade of arthritis such as grade 4. These patients still improved.

No serious side effects were noted from the treatment. There were also no systemic infections or reports of cancer upon any of the patient follow ups. This is also confirmed in the literature.

The hypothesis tests confirm 2 items as listed below.

  1. There is significant improvement in KOOS scores post treatment at the follow up intervals of 1 to 6 weeks.
    The average pre-operative KOOS score of patients were 37.5 and the post treatment KOOS score had increased to a 66.6. This has confirmed a large increase in the patients function and decrease in pain levels for their knee joints.
  2. The association of a patient with higher BMI does correlate with the patients KOOS score. Ie: the heavier a patient is it is likely they are going to have a lower KOOS score which indicates poor function and increased pain levels. They will also take longer to respond.

This studies result relied solely on the treatment of SVF and no other contributing factors such as analgesics, physical therapy or other medical inputs to aid in pain relief for the patients osteoarthritis.

 

REF: DOI: 10.18410/jebmh/2015/964 J of Evidence Based Med & Hlthcare, pISSN- 2349-2562, eISSN- 2349-2570/ Vol. 2/Issue 41/Oct. 12, 2015 Page 7088

Tags: Macquarie Stem Cells, Dr. Bright, Osteoarthritis Treatment, Dr. Ralph Bright, Stem Cell Therapy, Stem Cell Treatment, Stem Cells for Arthritis