Knee Problems
 

     Knee arthritis is a form of degenerative joint disease that affects millions of Americans. There are several alternatives to knee surgery such as injection of cartilage substitutes or steroids. Steroid injection is not favored as a viable long term treatment since the steroids actually damage local tissues over time. Certain types of knee problems including significant meniscal and ligamentous injuries may not be amenable to regenerative therapy. It is important to evaluate each individual case to assess likelihood of success with attempting regenerative therapy. CSN has developed a degenerative knee disease protocol that attempts to exploit the anti-inflammatory and healing effects of SVF (rich in mesenchymal stem cells and growth factors). The protocol uses PRP autologous platelet rich plasma to optimize the effects of the SVF. The deployment protocol performed under local anesthesia is all done as an outpatient at the time of SVF harvesting and procurement. The entire cellular surgical procedure takes approximately 3 hours.

     We care about our Knee patients at the Cell Surgical Network and take pride in the time that our dedicated physicians provide to our patients to deploy the best protocols to help our patients achieve their goals. By filling out Confidential Candidate Application, we will answer the questions and concerns you may have about Cell Surgical Network protocols for Knee problems.

 
CANDIDATE APPLICATION
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Cell Surgical Network Study for Stromal Vascular Fraction Registered by ClinicalTrials.gov

Rancho Mirage, CA (PRWEB) October 14, 2013

Clinicaltrials.gov, a service of the U.S. National Institutes of Health has registered on their public site an IRB approved safety study from the Cell Surgical Network, Inc.. This study is available for patients with various degenerative and inflammatory conditions to undergo Stromal Vascular Fraction deployment for the evaluation and for the advancement of future stem cell therapy procedures. Stromal Vascular Fraction is rich in autologous adipose derived stem cells and growth factors.

Stromal Vascular Fraction (SVF) is obtained by lipo-harvesting, procurement, and lipo-transfer as a same day operative procedure to provide therapy to patients with various degenerative and inflammatory diseases. Patients must be 16 years or older, male or female and have a degenerative disease or inflammatory disease that meets criteria for treatment under the IRB which includes: Arthritis, Auto-immune disease, COPD, Cardiomyopathy, Peyronies Disease, Interstitial Cystitis, Erectile Dysfunction, and Neurodegenerative disease such as Parkinson’s, ALS, Neuropathy. Patients must be healthy enough to tolerate a local anesthetic, must not have active cancer or infections.

Dr. Elliot Lander, and Dr. Mark Berman, founders of the Cell Surgical Network Inc. will conduct the study: “Ever since our inception, it’s been our goal to maintain transparency during our investigations. With a closed surgical procedure we can provide effective safety studies and evolve good empirical data that will allow us and others to ultimately refine our protocols,” says Dr. Berman.

The purpose of the safety study is to evaluate for any adverse effects that may be related to the administration and reception of autologous adipose derived stromal vascular fraction (SVF). Secondarily, the study monitors the results of subjective and objective findings as it applies to the non-blinded deployment of autologous SVF for various inflammatory and/or degenerative conditions including select orthopedic, neurologic, urologic and cardio-pulmonary conditions. SVF deployments include intra-venous, intra-articular, and soft tissue injections.

Outcome measures will include the number of participants with adverse events related to either SVF deployment or the lipo-harvesting procedure. Interested patients should contact the treatment center by phone: 800-231-0407 or via email: info(at)cellsurgicalnetwork(dot)com

About Cell Surgical Network:

The affiliates of the Cell Surgical Network (CSN) are devoted to advancing access and quality care in the area of adult stem cell regenerative medicine in order to help people suffering from a variety of inflammatory and degenerative conditions. The Cell Surgical Network was founded nearly two years after the formation of the California Stem Cell Treatment Center (founded in 2010). Affiliate members are generally made up of multi-state and international teams of multidisciplinary physicians in order to best assess and provide care for our patients. The Cell Surgical Network emphasizes quality and is highly committed to clinical research and the advancement of regenerative medicine.

 
Adipose derived mesenchymal stem cell therapy in the treatment of isolated knee chondral lesions: design of a randomised controlled pilot study comparing arthroscopic microfracture versus arthroscopic microfracture combined with postoperative mesenchymal stem cell injections.

BMJ Open. 2015 Dec 18;5(12):e009332. doi: 10.1136/bmjopen-2015-009332.

Authors: Freitag J, Ford J, Bates D, Boyd R, Hahne A, Wang Y, Cicuttini F, Huguenin L, Norsworthy C, Shah K.

Abstract
 
INTRODUCTION: The management of intra-articular chondral defects in the knee remains a challenge. Inadequate healing in areas of weight bearing leads to impairment in load transmission and these defects predispose to later development of osteoarthritis. Surgical management of full thickness chondral defects include arthroscopic microfracture and when appropriate autologous chondrocyte implantation. This latter method however is technically challenging, and may not offer significant improvement over microfracture. Preclinical and limited clinical trials have indicated the capacity of mesenchymal stem cells to influence chondral repair. The aim of this paper is to describe the methodology of a pilot randomised controlled trial comparing arthroscopic microfracture alone for isolated knee chondral defects versus arthroscopic microfracture combined with postoperative autologous adipose derived mesenchymal stem cell injections.

 

METHODS AND ANALYSIS: A pilot single-centre randomised controlled trial is proposed. 40 participants aged 18-50 years, with isolated femoral condyle chondral defects and awaiting planned arthroscopic microfracture will be randomly allocated to a control group (receiving no additional treatment) or treatment group (receiving postoperative adipose derived mesenchymal stem cell treatment). Primary outcome measures will include MRI assessment of cartilage volume and defects and the Knee Injury and Osteoarthritis Outcome Score. Secondary outcomes will include further MRI assessment of bone marrow lesions, bone area and T2 cartilage mapping, a 0-10 Numerical Pain Rating Scale, a Global Impression of Change score and a treatment satisfaction scale. Adverse events and cointerventions will be recorded. Initial outcome follow-up for publication of results will be at 12 months. Further annual follow-up to assess long-term differences between the two group will occur.

 

ETHICS AND DISSEMINATION: This trial has received prospective ethics approval through the Latrobe University Human Research Ethics Committee. Dissemination of outcome data is planned through both national and international conferences and formal publication in a peer-reviewed journal.
TRIAL REGISTRATION NUMBER: Australia and New Zealand Clinical Trials Register (ANZCTR Trial ID: ACTRN12614000812695).
 
Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial.

 Stem Cells Transl Med. 2016 Jul;5(7):847-56. doi: 10.5966/sctm.2015-0245. Epub 2016 May 23.
 

Authors: Pers YM, Rackwitz L, Ferreira R, Pullig O, Delfour C, Barry F, Sensebe L, Casteilla L, Fleury S, Bourin P, Noël D, Canovas F, Cyteval C, Lisignoli G, Schrauth J,Haddad D, Domergue S, Noeth U, Jorgensen C; ADIPOA Consortium.

Abstract
 

 Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 × 10(6) cells), medium dose (10 × 10(6)), and high dose (50 × 10(6)). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow-up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy.

 

SIGNIFICANCE: Although this phase I study included a limited number of patients without a placebo arm, it showed that local injection of autologous adipose-derived stem cells was safe and well tolerated in patients with knee osteoarthritis. This study also provides encouraging preliminary evidence of efficacy. Larger and controlled long-term studies are now mandatory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01585857.
 
 
Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix.

Biores Open Access. 2016 Aug 1;5(1):192-200. doi: 10.1089/biores.2016.0024. eCollection 2016.
 

Authors: Pak J, Lee JH, Park KS, Jeong BC, Lee SH.

Abstract
 
This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs) and homogenized extracellular matrix (ECM) in the form of adipose stromal vascular fraction (SVF), along with hyaluronic acid (HA) and platelet-rich plasma (PRP) activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA) patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI) data, functional rating index, range of motion (ROM), and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees.
 
 
Adipose-Derived Mesenchymal Stem Cells With Microfracture Versus Microfracture Alone: 2-Year Follow-up of a Prospective Randomized Trial.

 Arthroscopy. 2016 Jan;32(1):97-109. doi: 10.1016/j.arthro.2015.09.010. Epub 2015 Nov 14.

Authors: Koh YG, Kwon OR, Kim YS, Choi YJ, Tak DH.

Abstract
 
PURPOSE: To compare the clinical and radiologic efficacy of adipose-derived stem cells (ADSCs) with fibrin glue and microfracture (MFX) versus MFX alone in patients with symptomatic knee cartilage defects.

 

METHODS: Patients who were aged 18 to 50 years and had a single International Cartilage Repair Society grade III/IV symptomatic cartilage defect (≥3 cm(2)) on the femoral condyle were randomized to receive ADSCs with fibrin glue and MFX treatment (group 1, n = 40) or MFX treatment alone (group 2, n = 40). There was a lack of blinding for patients because of the additional intervention method (liposuction). The cartilage defect was diagnosed using preoperative magnetic resonance imaging (MRI), and quantitative and qualitative assessments of the repair tissue were carried out at 24 months by using the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system with follow-up MRI. Clinical results were evaluated using the Lysholm score, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and a 10-point visual analog scale for pain (0 points, no pain; 10 points, worst possible pain) preoperatively and postoperatively at 3 months, 12 months, and the last follow-up visit.

 

RESULTS: The 2 groups had similar baseline patient characteristics. Follow-up MRI was performed at 24 months (mean, 24.3 months; range, 24.0 to 25.1 months) after the operation. Group 1 included 26 patients (65%) who had complete cartilage coverage of the lesion at follow-up compared with 18 patients (45%) in group 2. Significantly better signal intensity was observed for the repair tissue in group 1, with 32 patients (80%) having normal or nearly normal signal intensity (i.e., complete cartilage coverage of the lesion) compared with 28 patients (72.5%) in group 2. The mean clinical follow-up period was 27.4 months (range, 26 to 30 months). The improvements in the mean KOOS pain and symptom subscores were significantly greater at follow-up in group 1 than in group 2 (pain, 36.6 ± 11.9 in group 1 and 30.1 ± 14.7 in group 2 [P = .034]; symptoms, 32.3 ± 7.2 in group 1 and 27.8 ± 6.8 in group 2 [P = .005]). However, the improvements in the other subscores were not significantly different between group 1 and group 2 (activities of daily living, 38.5 ± 12.8 and 37.6 ± 12.9, respectively [P = .767]; sports and recreation, 33.9 ± 10.3 and 31.6 ± 11.0, respectively [P = .338]; quality of life, 38.4 ± 13.1 and 37.8 ± 12.0, respectively [P = .650]). Among the 80 patients, second-look arthroscopies were performed in 57 knees (30 in group 1 and 27 in group 2), and biopsy procedures were performed during these arthroscopies for 18 patients in group 1 and 16 patients in group 2. The second-look arthroscopies showed good repair tissue quality, although no significant intergroup difference was observed. The mean total histologic score was 1,054 for group 1 compared with 967 for group 2 (P = .036). Age, lesion size, duration of symptoms before surgery, mechanism of injury, and combined procedures were not correlated with clinical results, Magnetic Resonance Observation of Cartilage Repair Tissue scores, and histologic outcomes at short-term follow-up.
CONCLUSIONS: Compared with MFX alone, MFX and ADSCs with fibrin glue provided radiologic and KOOS pain and symptom subscore improvements, with no differences in activity, sports, or quality-of-life subscores, in symptomatic single cartilage defects of the knee that were 3 cm(2) or larger, with similar structural repair tissue.
 
 
Intra-articular injection in the knee of adipose derived stromal cells (stromal vascular fraction) and platelet rich plasma for osteoarthritis.

J Transl Med. 2017 Jun 19;15(1):141. doi: 10.1186/s12967-017-1242-4.

Authors:Bansal H, Comella K, Leon J, Verma P, Agrawal D, Koka P6, Ichim T7.

 

Abstract

 

BACKGROUND:  Stromal vascular fraction (SVF) can easily be obtained from a mini-lipoaspirate procedure of fat tissue and platelet rich plasma (PRP) can be obtained from peripheral blood. We evaluated the safety and preliminary efficacy of administering SVF and PRP intra-articularly into patients with osteoarthritis grade 1 and 2.

 

METHODS: A total of ten patients underwent a local tumescent liposuction procedure to remove approximately 100 ml of fat tissue from the abdomen. SVF was isolated using an enzyme digestion and resuspended in PRP for intra-articular injection in the knee. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and six-minute walk distance (6MWD) were used to evaluate clinical effects and included measure of patient's subjective assessment of pain, joint mobility, and physical disability. WOMAC score, 6MWD and laboratory tests were repeated at 3 and 6 months and 1, 1.5 and 2 years. XRAY and MRI were completed at 1 year.

 

RESULTS: The average total WOMAC score was 64 at baseline and significantly reduced to 52 at 3 months, 46 at 6 months, 42 at 1 year, 38 at 1.5 years, and 41 at 2 years. Patients walked an average of 1310 feet at baseline and demonstrated a statistically significant improvement at 3 and 6 months and 1, 1.5, and 2 years post treatment. Cartilage thickness as determined by MRI improved by at least 0.2 mm in six patients, was unchanged in two patients and decreased by at least 0.2 mm in two patients.

 

CONCLUSIONS: Overall, all of the patients were pleased with the treatment results. They reported a reduction in pain levels, especially after 3 months. More importantly, the procedure demonstrated a strong safety profile with no severe adverse events or complications reported. Trial registration NCT03089762; Name of registry: http://www.clinicaltrials.gov.

 
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