Low back pain (LBP) can significantly reduce the quality of life of patients, and has a considerable economic and social impact worldwide. It is commonly associated with disc degeneration, even though many people with degenerate discs are asymptomatic. Degenerate disc disease (DDD), is thus a common term for intervertebral disc (IVD) degeneration associated with LBP. Degeneration is thought to lead to LBP because of nerve ingrowth into the degenerate disc, inflammation, or because degradation of extracellular matrix (ECM) alters spinal biomechanics inappropriately. Thus, while the objectives of some interventions for LBP are to control pain intensity, other interventions aim to deal with the consequences of disc degeneration through stabilizing the disc surgically, by inserting artificial discs or by repairing the disc biologically and preventing progressive IVD degeneration. Despite tremendous research efforts, treatment of LBP through the use of regenerative interventions aiming to repair the IVD is still controversial. The use of mesenchymal stem cells for IVD regeneration in a patient‐based case will be discussed by an ensemble of clinicians and researchers.
Blood supply is a critical issue in most tissue engineering approaches for large defect healing. As vessel ingrowth from surrounding tissues is proven to be insufficient, current strategies are focusing on the neo-vascularisation process. In the present study, we developed an in vitro pre-vascularised construct using 3D polyurethane (PU) scaffolds, based on the association of human Endothelial Progenitor Cells (EPC, CD34+ and CD133+) with human Mesenchymal Stem Cells (MSC). We showed the formation of luminal tubular structures in the co-seeded scaffolds as early as day 7 in culture. These tubular structures were proven positive for endothelial markers von Willebrand Factor and PECAM-1. Of special significance in our constructs is the presence of CD146-positive cells, as a part of the neovasculature scaffolding. These cells, coming from the mesenchymal stem cells population (MSC or EPC-depleted MSC), also expressed other markers of pericyte cells (NG2 and αSMA) that are known to play a pivotal function in the stabilisation of newly formed pre-vascular networks. In parallel, in co-cultures, osteogenic differentiation of MSCs occurred earlier when compared to MSCs monocultures, suggesting the close cooperation between the two cell populations. The presence of angiogenic factors (from autologous platelet lysates) in association with osteogenic factors seems to be crucial for both cell populations' cooperation. These results are promising for future clinical applications, as all components (cells, growth factors) can be prepared in an autologous way.
18 September 2008 in The American Journal of Sports Medicine
Background: There is a lack of detailed information about habitual physical activity levels and the sports participation of patients after total ankle arthroplasty. Hypothesis: The proportion of sports active patients increases after total ankle arthroplasty, and the majority of patients will meet current recommendations for health-enhancing physical activity. Study Design: Case series; Level of evidence, 4. Methods: The authors assessed the pre- and postoperative participation in sports and recreational activities of 101 patients at a mean of 3.7 years after total ankle arthroplasty. Activity levels were determined with use of the University of California at Los Angeles (UCLA) activity scale. The International Physical Activity Questionnaire (IPAQ) was used to quantify habitual physical activity levels and to calculate the proportion of patients meeting current guidelines for health-enhancing physical activity. The American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score was used as the clinical outcome measure. Radiographs were studied for tibial and talar radiolucencies, and any association between radiolucencies, activity levels, and sports participation was determined. Results: Preoperatively, 62.4% of the patients were active in sports; 66.3% were active after surgery (P = .56). The patients were active in 3.0 ± 1.8 different sports and recreational activities preoperatively and in 3.0 ± 1.6 activities after surgery (P = 1.0). The sports frequency remained unchanged, with 2.0 ± 1.6 sessions per week before total ankle arthroplasty and 2.3 ± 1.7 sessions per week postoperatively (P = .19). Overall, the patients were active in sports and recreation for 3.9 ± 3.8 hours per week preoperatively, and for 4.7 ± 3.9 hours per week after surgery (P = .14). The most common disciplines after total ankle arthroplasty were swimming, cycling, and fitness/weight training. Sixty-five percent of the patients stated that surgery had improved their sports ability. The UCLA activity levels increased significantly from 4.3 ± 2.2 to 6.2 ± 1.6 (P < .001); AOFAS scores also improved significantly from 45.5 ± 16.6 to 84.3 ± 13.3 (P < .001). Patients suffering from posttraumatic ankle osteoarthritis were less satisfied with surgery than those with primary or inflammatory ankle osteoarthritis. Seventy-nine percent of the patients met the current guidelines for health-enhancing physical activity according to the IPAQ. Neither sports participation nor activity levels were associated with the presence of periprosthetic radiolucencies. Conclusion: Two-thirds of the patients were active in sports after total ankle arthroplasty, and the majority of the patients met current health-enhancing physical activity recommendations. The clinical outcome as determined by AOFAS scores and the patient satisfaction were favorable. The present study found no association between sports participation, increased physical activity levels, and the appearance of periprosthetic radiolucencies 3.7 years after total ankle arthroplasty. However, these results have to be confirmed after longer follow-up, in particular of those patients regularly participating in sports with higher impact.
Tissue engineering techniques for the regeneration of large bone defects require sufficient vascularisation of the applied constructs to ensure a sufficient supply of oxygen and nutrients. In our previous work, prevascularised 3D scaffolds have been successfully established by coculture of bone marrow derived stem cells (MSCs) and endothelial progenitor cells (EPCs). We identified stabilising pericytes (PCs) as part of newly formed capillary-like structures. In the present study, we report preliminary data on the interactions between MSCs and EPCs, leading to the differentiation of pericyte-like cells. MSCs and EPCs were seeded in transwell cultures, direct cocultures, and single cultures. Cells were cultured for 10 days in IMDM 10% FCS or IMDM 5% FCS 5% platelet lysate medium. Gene expression of PC markers, CD146, NG2,αSMA, and PDGFR-β, was analysed using RT-PCR at days 0, 3, 7, and 10. The upregulation of CD146, NG2, andαSMA in MSCs in direct coculture with EPCs advocates the MSCs’ differentiation towards a pericyte-like phenotype in vitro. These results suggest that pericyte-like cells derive from MSCs and that cell-cell contact with EPCs is an important factor for this differentiation process. These findings emphasise the concept of coculture strategies to promote angiogenesis for cell-based tissue engineered bone grafts.