Cell Transplant. 2015 Jan 20. doi: 10.3727/096368915X686760. [Epub ahead of print]
Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis.
Michalek J1, Moster R, Lukac L, Proefrock K, Petrasovic M, Rybar J, Capkova M, Chaloupka A, Darinskas A, Michalek J Sr, Kristek J, Travnik J, Jabandziev P, Cibulka M, Holek M, Jurik M, Skopalik J, Kristkova Z,Dudasova Z.
11International Consortium for Cell Therapy and Immunotherapy, Brno, Czech Republic,.
Stromal vascular fraction (SVF), containing large amount of stem cells and other regenerative cells, can be easily obtained from loose connective tissue that is associated with adipose tissue. Here we evaluated safety and clinical efficacy of freshly isolated autologous SVF cells in a case control study in patients with grade 2-4 degenerative osteoarthritis (OA). A total of 1128 patients underwent standard liposuction under local anesthesia and SVF cells were isolated and prepared for application into 1-4 large joints. A total of 1856 joints, mainly knee and hip joints, were treated with a single dose of SVF cells. 1114 patients were followed for 12.1-54.3 months (median 17.2 months) for safety and efficacy. Modified KOOS/HOOS Clinical Score was used to evaluate clinical effect and was based on pain, non-steroid analgesic usage, limping, extent of joint movement, and stiffness evaluation before and at 3, 6, and 12 months after the treatment. No serious side effects, systemic infection or cancer was associated with SVF cell therapy. Most patients gradually improved 3-12 months after the treatment. At least 75% Score improvement was noticed in 63% of patients and at least 50% Score improvement was documented in 91% of patients 12 months after SVF cell therapy. Obesity and higher grade of OA were associated with slower healing. In conclusion, here we report a novel and promising treatment approach for patients with degenerative OA that is safe, cost-effective, and relying only on autologous cells.
Biores Open Access. 2016 Aug 1;5(1):192-200. doi: 10.1089/biores.2016.0024. eCollection 2016.
Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix.
1Stems Medical Clinic, Seoul, Republic of Korea.; TEDA-Puhua International Hospital, Tianjin, China.; Life Science Institute, Komplek Permata Senayan, Jalan Tentara Pelajar, Jakarta Selatan, Indonesia.
2Stems Medical Clinic, Seoul, Republic of Korea.; National Leading Research Laboratory, Department of Biological Sciences, Myongji University, Yongin, Republic of Korea.
3National Leading Research Laboratory, Department of Biological Sciences, Myongji University , Yongin, Republic of Korea.
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 physicaltherapy 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 tissue-derived stem cells; extracellular matrix; human cartilage regeneration; osteoarthritis
Clin Transl Med. 2016 Dec;5(1):27. doi: 10.1186/s40169-016-0112-7. Epub 2016 Aug 10.
Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis.
1Department of Orthopedics, Georgia Regents University, Augusta, GA, USA.
2Department of Pathology, Georgia Regents University, Augusta, GA, USA.
3Institute of Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, USA.
4Department of Cell Biology and Anatomy, Georgia Regents University, Augusta, GA, USA.
5Department of Orthopedics, Georgia Regents University, Augusta, GA, USA. firstname.lastname@example.org.
6Institute of Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, USA. email@example.com.
7Department of Orthopedics Surgery, Augusta University, Augusta, GA, 30904, USA.
Osteoarthritis (OA) is a chronic degenerative disease affecting articular cartilage in joints, and it is a leading cause of disability in the United States. Current pharmacological treatment strategies are ineffective to prevent the OA progression; however, cellular therapies have the potential to regenerate the lost cartilage, combat cartilage degeneration, provide pain relief, and improve patient mobility. One of the most promising sources of cellular regenerative medicine is from mesenchymal stem cells (MSCs). MSCs can be isolated from adipose tissue, bone marrow, synovial tissue, and other sources. The aim of this review is to compile recent advancement in cellular based therapy more specifically in relation to MSCs in the treatment of osteoarthritis.
ADSC; Cell therapy; Osteoarthritis; Stem cell
J Orthop Surg Res. 2016 Apr 12;11:42. doi: 10.1186/s13018-016-0378-x.
Stem cells in articular cartilage regeneration.
1II Orthopaedic and Traumatologic Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy.
2Nanobiotechnology Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136, Bologna, Italy. firstname.lastname@example.org.
3Nanobiotechnology Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136, Bologna, Italy.
Mesenchymal stem cells (MSCs) have emerged as a promising option to treat articular defects and early osteoarthritis (OA) stages. However, both their potential and limitations for a clinical use remain controversial. Thus, the aim of this systematic review was to examine MSCs treatment strategies in clinical settings, in order to summarize the current evidence of their efficacy for the treatment of cartilage lesions and OA.Among the 60 selected studies, 7 were randomized, 13 comparative, 31 case series, and 9 case reports; 26 studies reported the results after injective administration, whereas 33 used surgical implantation. One study compared the two different modalities. With regard to the cell source, 20 studies concerned BMSCs, 17 ADSCs, 16 BMC, 5 PBSCs, 1 SDSCs, and 1 compared BMC versus PBSCs. Overall, despite the increasing literature on this topic, the evidence is still limited, in particular for high-level studies. On the other hand, the available studies allow to draw some indications. First, no major adverse events related to the treatment or to the cell harvest have been reported. Second, a clinical benefit of using MSCs therapies has been reported in most of the studies, regardless of cell source, indication, or administration method. This effectiveness has been reflected by clinical improvements and also positive MRI and macroscopic findings, whereas histologic features gave more controversial results among different studies. Third, young age, lower BMI, smaller lesion size for focal lesions, and earlier stages of OA joints have been shown to correlate with better outcomes, even though the available data strength does not allow to define clear cutoff values. Finally, definite trends can be observed with regard to the delivery method: currently cultured cells are mostly being administered by i.a. injection, while one-step surgical implantation is preferred for cell concentrates. In conclusion, while promising results have been shown, the potential of these treatments should be confirmed by reliable clinical data through double-blind, controlled, prospective and multicenter studies with longer follow-up, and specific studies should be designed to identify the best cell sources, manipulation, and delivery techniques, as well as pathology and disease phase indications.
Stem Cells. 2014 Apr 17. doi:10.1002/stem.1634
Intra-Articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritis of the Knee: A Proof-of-Concept Clinical Trial
Jo CH1, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, Kim JE, Shim H, Shin JS, Shin IS, Ra JC, Oh S, Yoon KS
1Department of Orthopedic Surgery, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea.
Mesenchymal stem cells (MSCs) are known to have a potential for articular cartilage regeneration. However, most studies focused on focal cartilage defect through surgical implantation. For the treatment of generalized cartilage loss in osteoarthritis, an alternative delivery strategy would be more appropriate. The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs (AD-MSCs) for knee osteoarthritis. We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee. The phase I study consists of three dose-escalation cohorts; the low-dose (1.0 × 10(7) cells), mid-dose (5.0 × 10(7)), and high-dose (1.0 × 10(8)) group with three patients each. The phase II included nine patients receiving the high-dose. The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) at 6 months. Secondary outcomes included clinical, radiological, arthroscopic, and histological evaluations. There was no treatment-related adverse event. The WOMAC score improved at 6 months after injection in the high-dose group. The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group. Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group. Histology demonstrated thick, hyaline-like cartilage regeneration. These results showed that intra-articular injection of 1.0 × 10(8) AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events, and reduced cartilage defects by regeneration of hyaline-like articular cartilage.
CellR4. 2016 Feb 05. 4 (1): e1768
Adipose-derived stromal vascular fraction (SVF) for the treatment of osteoarthritis of the knee, functional outcome and anatomic recovery of the cartilage: a case report
Correa D1, Gomez A2,3, Vargas C2,3, Turner E4, Carstens MH2,3,5.
1 Department of Orthopaedics (Division of Sports Medicine), and the Diabetes Research Institute & Cell Transplant Center, University of Miami, Miller School of Medicine, Miami, FL, USA
2 Division of Plastic Surgery, Hospital Metropolitano Vivian Pellas, Managua, Nicaragua
3 Professor of Surgery, Universidad Nacional Autónoma de Nicaragua, Leon, Nicaragua
4 Director of Bedside Ultrasound, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA
5 Clinical Associate Professor of Plastic Surgery, Saint Louis University, Saint Louis, MO, USA
Background: Osteoarthritis (OA) is a degenerative debilitating disease characterized by progressive erosion of the articular cartilage. Current treatment approaches are reduced to control the associated symptoms, leaving the degenerative changes to progress until a joint replacement becomes mandatory. Therefore, disease-modifying therapeutic alternatives are warranted to improve the patient’s quality of life as well as to ameliorate the high economic impact this disease pose on the healthcare system.
Objective: We present a case study of a 42-year-old male with stage 3-4 (clinical) and grade 3 and 4 (radiological) OA, to support the evidence of a positive effect of intra-articularly injected Mesenchymal Stem Cells (MSC)-containing adipose-derived stromal vascular fraction (SVF) on both clinical and articular cartilage structural outcomes.
Materials and Methods: To obtain the SVF, the patient underwent liposuction and the lipoaspirate was enzymatically processed. The resulting SVF was locally injected into the knee joint. Resultant symptomatology was assessed using the KOOS (Knee Osteoarthritis Objective Score) and the structural response was documented using ultrasonography, both evaluated at various time-points.
Results: We observed the largest clinical improvement (~130% in the KOOS score) in the first 6 weeks, stabilized at 24 weeks, and persisted at 20 month. Notable, ultrasonographic changes included progressive widening of joint spaces, elimination of effusions and thickening of articular cartilage that started as early as 6 weeks and persisted throughout the evaluation period.
Conclusions: Cell-based therapy for advanced knee OA using MSC-containing adipose-derived SVF was subjectively and objectively positive for the patient. The KOOS and ultrasonographic measurements were simple and aligned with the patient’s course response, providing additional evidence of a positive effect both clinically and structurally. In addition, the results here highlight the importance of consecutive measurements with an inexpensive approach to appreciate the biological process of such therapy for OA and to establish a response curve.
Biomedical research and therapy. 2014 Feb 07. doi: 10.7603/s40730-014-0002-9
Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study
Bui KHT1, Duong TD1, Nguyen NT1, Nguyen TD1, Le VT1, Mai VT1, Phan NLC2, Le DM2, Ngoc NK2, Pham PV2.
1University of Medical Center, Ho Chi Minh University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam
2Laboratory of Stem Cell Re-search and Application, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam
Osteoarthritis is one of the most common diseases, and it affects 12% of the population around the world. Although the disease is chronic, it significantly reduces the patient’s quality of life. At present, stem cell therapy is considered to be an efficient approach for treating this condition. Mesenchymal stem cells (MSCs) show the most potential for stem cell therapy of osteoarthritis. In fact, MSCs can differentiate into certain mesodermal tissues such as cartilage and bone. Therefore, in the present study, we applied adipose tissue-derived MSCs to osteoarthritis treatment. This study aimed to evaluate the clinical efficiency of autologous adipose tissue-derived MSC transplantation in patients with confirmed osteoarthritis at grade II and III. Adipose tissue was isolated from the belly, and used for extraction of the stromal vascular fraction (SVF). The SVF was mixed with activated platelet- rich plasma before injection. The clinical efficiencies were evaluated by the pain score (VAS), Lysholm score, and MRI findings. We performed the procedure in 21 cases from 2012 to 2013. All 21 patients showed improved joint function after 8.5 months. The pain score decreased from 7.6±0.5 before injection to 3.5±0.7 at 3 months and 1.5±0.5 at 6 months after injection. The Lysholm score increased from 61±11 before injection to 82±8.1 after injection. Significant improvements were noted in MRI findings, with increased thickness of the cartilage layer. Moreover, there were no side-effects or complications related to microorganism infection, graft rejection, or tumorigenesis. These results provide a new opportunity for osteoarthritis treatment. Level of evidence: IV.
Exp Ther Med. 2016 Oct 11. doi: 10.3892/etm.2016.3791
Efficacy of mesenchymal stem cells in treating patients with osteoarthritis of the knee: A meta-analysis
Cui GH1, Wang YY, Li CJ, Shi CH, Wang WS.
1Department of Orthopedics, Medical College of Shihezi University, Shihezi, Xinjiang 832008, P.R. China
To assess the clinical efficacy and safety of mesenchymal stem cell (MSC) treatment for osteoarthritis of the knee (KOA), a systematic electronic literature search was performed on PubMed, EMBASE and Web of Science. Studies published in English from the earliest record to December 2014 were searched using the following keywords: Cartilage defect, cartilage repair, osteoarthritis, KOA, stem cells, MSCs, bone marrow concentrate (BMC), adipose-derived mesenchymal stem cells, synovial-derived mesenchymal stem cells and peripheral blood-derived mesenchymal stem cells. The effect sizes of selected studies were determined by extracting pain scores from the visual analog scale and functional changes from International Knee Documentation Committee and Lysholm and Western Ontario and McMaster Universities Osteoarthritis Index before and after MSCs or reference treatments at 3, 6, 12, and 24 months. The factors were analyzed and the outcomes were modified after comparing the MSC group pooled values with the pretreatment baseline or between different treatment arms. A systematic search identified 18 clinical trials on this topic, including 10 single-arm prospective studies, four quasi-experimental studies and four randomized controlled trials that used BMCs to treat 565 patients with KOA in total. MSC treatment in patients with KOA showed continual efficacy for 24 months compared with their pretreatment condition. Effectiveness of MSCs was improved at 12 and 24 months post-treatment, compared with at 3 and 6 months. No dose-responsive association in the MSCs numbers was demonstrated. However, patients with arthroscopic debridement, activation agent or lower degrees of Kellgren-Lawrence grade achieved improved outcomes. MSC application ameliorated the overall outcomes of patients with KOA, including pain relief and functional improvement from basal evaluations, particularly at 12 and 24 months after follow-up.