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.
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.
Knee Surg Sports Traumatol Arthrosc. 2013 Aug;21(8):1717-29. doi: 10.1007/s00167-012-2329-3. Epub 2013 Jan 11.
Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics.
1Biomechanics Laboratory, III Clinic, Rizzoli Orthopaedic Institute, Via Di Barbiano, 1/10, 40136, Bologna, Italy.
The aim of this systematic review is to examine the available clinical evidence in the literature to support mesenchymal stem cell (MSC) treatment strategies in orthopaedics for cartilage defect regeneration.
The research was performed on the PubMed database considering the English literature from 2002 and using the following key words: cartilage, cartilage repair, mesenchymal stem cells, MSCs, bone marrow concentrate (BMC), bone marrow-derived mesenchymal stem cells, bone marrow stromal cells, adipose-derived mesenchymal stem cells, and synovial-derived mesenchymal stem cells.
The systematic research showed an increasing number of published studies on this topic over time and identified 72 preclinical papers and 18 clinical trials. Among the 18 clinical trials identified focusing oncartilage regeneration, none were randomized, five were comparative, six were case series, and seven were case reports; two concerned the use of adipose-derived MSCs, five the use of BMC, and 11 the use of bone marrow-derived MSCs, with preliminary interesting findings ranging from focal chondral defects to articular osteoarthritis degeneration.
Despite the growing interest in this biological approach for cartilage regeneration, knowledge on this topic is still preliminary, as shown by the prevalence of preclinical studies and the presence of low-quality clinical studies. Many aspects have to be optimized, and randomized controlled trials are needed to support the potential of this biological treatment for cartilage repair and to evaluate advantages and disadvantages with respect to the available treatments.