Knee Surg Sports Traumatol Arthrosc. 2016 Jun;24(6):1826-35. doi: 10.1007/s00167-016-4125-y. Epub 2016 Apr 27.
Regenerative approaches for the treatment of early OA.
1Orthopaedic Biotechnology Laboratory, Galeazzi Orthopaedic Institute, Milan, Italy. email@example.com.
2II Orthopedic Division and NanoBiotechnology Lab, Rizzoli Orthopedic Institute, Bologna, Italy.
3Department of Orthopaedics and Traumatology, University of Torino, Turin, Italy.
4Molecular Biotechnology Center, University of Torino, Turin, Italy.
5ITRT Centro Médico Teknon, Barcelona, Spain.
6Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
7Galeazzi Orthopaedic Institute, Milan, Italy.
8I Clinic of Orthopaedics and Traumatology, Rizzoli Orthopaedic Institute, Bologna, Italy.
9Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany.
10Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg/Saar, Germany.
11Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA.
The diagnosis and the prompt treatment of early osteoarthritis (OA) represent vital steps for delaying the onset and progression of fully blown OA, which is the most common form of arthritis, involving more than 10 % of the world’s population older than 60 years of age. Nonsurgical treatments such as physiotherapy, anti-inflammatory medications, and other disease-modifying drugs all have modest and short-lasting effect. In this context, the biological approaches have recently gained more and more attention. Growth factors, blood derivatives, such as platelet concentrates, and mesenchymal adult stem cells, either expanded or freshly isolated, are advocated amongst the most promising tool for the treatment of OA, especially in the early phases. Primarily targeted towards focal cartilage defects, these biological agents have indeed recently showed promising results to relieve pain and reduce inflammation in patients with more advanced OA as well, with the final aim to halt the progression of the disease and the need for joint replacement. However, despite of a number of satisfactory in vitro and pre-clinical studies, the evidences are still limited to support their clinical efficacy in OA setting.
Cartilage; Growth factors; Mesenchymal stem cells; Molecular therapy; Osteoarthritis
J Pain Res. 2015 Nov 9;8:799-806. doi: 10.2147/JPR.S92090. eCollection 2015.
Management of knee osteoarthritis by combined stromal vascular fraction celltherapy, platelet-rich plasma, and musculoskeletal exercises: a case series.
1South Sydney Sports Medicine, Kensington, Australia.
2Diamond Health Care, Kensington, Australia.
3Endeavour College of Natural Health, Sydney, Australia.
4Cell-Innovations Pty Ltd, Liverpool, NSW, Australia.
Knee osteoarthritis is associated with persistent joint pain, stiffness, joint deformities, ligament damage, and surrounding muscle atrophy. The complexity of the disease makes treatment difficult. There are no therapeutic drugs available to halt the disease progression, leaving patients dependent on painmedication, anti-inflammatory drugs, or invasive joint replacement surgery.
Four patients with a history of unresolved symptomatic knee osteoarthritis were investigated for the therapeutic outcome of combining an exercise rehabilitation program with intra-articular injections of autologous StroMed (ie, stromal vascular fraction cells concentrated by ultrasonic cavitation from lipoaspirate) and platelet-rich plasma (PRP). The Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) was administered along with physical function tests over a 12-month period. The first patient achieved a maximum therapeutic outcome of 100 in all five KOOS subscales (left knee), and 100 for four subscales (right knee). The second patient scored 100 in all five KOOS subscales (left knee), and greater than 84 in all subscales (right knee). Treatment of the third patient resulted in improved outcomes in both knees of >93 for four KOOS subscales, and 60 for the Function in Sport and Recreation subscale. The fourth patient improved to 100 in all five KOOS subscales. In all patients, the physical function “Get-up and Go” test and “Stair Climbing Test” returned to normal (a value of zero).
This case series indicates that improved outcomes may be obtained when autologous stromal vascular fraction (StroMed) cell therapy is combined with traditional exercise practices and PRP for osteoarthritis. Of the seven joints treated: all patients’ scores of pain improved to >96; and quality of life scores to >93. Functional performance measures of mobility returned to normal. This simple treatment appears to be extremely effective for osteoarthritis disorders that have no drug treatment to halt disease progression.
SVF; StroMed; autologous stromal cell concentrate; joint; mesenchymal stem cells; pain
Methods. 2016 Apr 15;99:69-80. doi: 10.1016/j.ymeth.2015.09.015. Epub 2015 Sep 15.
Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration.
1Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom. Electronic address: firstname.lastname@example.org.
2Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), Faculty of Applied Medical Sciences, King AbdulAziz University, Jeddah 21589, Saudi Arabia. Electronic address: email@example.com.
3Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), Faculty of Applied Medical Sciences, King AbdulAziz University, Jeddah 21589, Saudi Arabia. Electronic address: firstname.lastname@example.org.
4Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom. Electronic address: email@example.com.
5Center for Nanotechnology and Department of Physics, King AbdulAziz University, Jeddah 21589, Saudi Arabia. Electronic address: firstname.lastname@example.org.
6Biomaterials Innovation Research Centre and Division of Biomedical Engineering, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea. Electronic address: email@example.com.
7Imperial Healthcare NHS Trust, Department of Orthopaedics, Salton House, St. Mary’s Hospital, London W2 1NY, United Kingdom. Electronic address: firstname.lastname@example.org.
8Imperial Healthcare NHS Trust, Department of Orthopaedics, Salton House, St. Mary’s Hospital, London W2 1NY, United Kingdom. Electronic address: Fabian.email@example.com.
9Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom; NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academic Health Science Centre, Manchester M13 9WL, United Kingdom. Electronic address: firstname.lastname@example.org.
10Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom; Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Arthritis Research UK Pain Centre, Medical Research Council and Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, United Kingdom; Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), Faculty of Applied Medical Sciences, King AbdulAziz University, Jeddah 21589, Saudi Arabia.
Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that can effectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs) show considerable promise for use in cartilage and intervertebral disc (IVD) repair. This review article focuses on stem cell-based therapeutics for cartilage and IVD repair in the context of the rising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitor cells and specifically focus on umbilical cord/Wharton’s jelly derived MSCs and examine their potential for regenerative applications. We also summarize key components of the molecular machinery and signaling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and biomaterials for articular cartilage and IVD regeneration. This review explores the exciting opportunities afforded by MSCs and discusses the challenges associated with cartilage and IVD repair and regeneration. There are still many technical challenges associated with isolating, expanding, differentiating, and pre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, the prospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondroprogenitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significant breakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.
Adipose-derived stem cell (AD-MSC); Articular cartilage; Biological therapy; Cellular therapy; IVD degeneration; Intervertebral disc (IVD); Low back pain (LBP); Mesenchymal stem cell (MSC); Osteoarthritis (OA); Regenerative medicine; Tissue engineering; Umbilical cord; Wharton’s Jelly stem cell (WJSC)
Aesthet Surg J. 2015 Aug 03. doi: https://doi.org/10.1093/asj/sjv135
Adipose Derived Stromal Cell (ADSC) Injections for Pain Management of Osteoarthritis in the Human Knee Joint
Fodor PB1, Paulseth SG2
1UCLA Medical Center, Los Angeles, USA
2Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, USA
This safety and feasibility study used autologous adipose-derived stromal vascular cells (the stromal vascular fraction [SVF] of adipose tissue), to treat 8 osteoarthritic knees in 6 patients of grade I to III (K-L scale) with initial pain of 4 or greater on a 10-point Visual Analog Scale (VAS).
The primary objective of the study was evaluation of the safety of intra-articular injection of SVF. The secondary objective was to assess initial feasibility for reduction of pain in osteoarthritic knees.
Adipose-derived SVF cells were obtained through enzymatic disaggregation of lipoaspirate, resuspension in 3 mL of Lactated Ringer’s Solution, and injection directly into the intra-articular space of the knee, with a mean of 14.1 million viable, nucleated SVF cells per knee. Metrics included monitoring of adverse events and preoperative to postoperative changes in the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the VAS pain scale, range of motion (ROM), timed up-and-go (TUG), and MRI.
No infections, acute pain flares, or other adverse events were reported. At 3-months postoperative, there was a statistically significant improvement in WOMAC and VAS scores ( P < .02 and P < .001, respectively), which was maintained at 1 year. Physical therapy measurements for ROM and TUG both improved from preoperative to 3-months postoperative. Standard MRI assessment from preoperative to 3-months postoperative showed no detectable structural differences. All patients attained full activity with decreased knee pain.
Autologous SVF was shown to be safe and to present a new potential therapy for reduction of pain for osteoarthritis of the knee.