The use of mesenchymal stromal cells (MSCs) in regenerative medicine and tissue engineering is well established, given their properties of self-renewal and differentiation. However, several studies have shown that these properties diminish with age, and understanding the pathways involved are important to provide regenerative therapies in an ageing population. In this PRISMA systematic review, we investigated the effects of chronological donor ageing on the senescence of MSCs. We identified 3023 studies after searching four databases including PubMed, Web of Science, Cochrane, and Medline. Nine studies met the inclusion and exclusion criteria and were included in the final analyses. These studies showed an increase in the expression of p21, p53, p16, ROS, and NF- B with chronological age. This implies an activated DNA damage response (DDR), as well as increased levels of stress and inflammation in the MSCs of older donors. Additionally, highlighting the effects of an activated DDR in cells from older donors, a decrease in the expression of proliferative markers including Ki67, MAPK pathway elements, and Wnt/ -catenin pathway elements was observed. Furthermore, we found an increase in the levels of SA- -galactosidase, a specific marker of cellular senescence. Together, these findings support an association between chronological age and MSC senescence. The precise threshold for chronological age where the reported changes become significant is yet to be defined and should form the basis for further scientific investigations. The outcomes of this review should direct further investigations into reversing the biological effects of chronological age on the MSC senescence phenotype.
The procedure was always performed with the patient in lateral position through a lateral transgluteal approach. We did not perform osteotomies of the greater trochanter or femur shortening osteotomies and the cup was placed where there was sufficient bone stock. The major determining factor in cup stability was the presence of sufficient anterior and posterior column. We also tried to insert the cup as medial as possible although in about half the group (25 out of 48), cup placement was superior and lateral. The limb length discrepancy was corrected by varying the neck length of the implant. A special stem was used in 5 cases. The mean intraoperative time was 65 mins with minimal soft tissue disruption as compared with the classic methods. The patients were mobilized postoperatively in a couple of days.
The purpose of this study is to present the clinical and radiological evaluation of 632 resurfacing total knee arthroplasties of Foundation-Solution type, performed in 550 patients (437 women and 113 men), from 1994 to 2003. In the majority of cases (569 knees) the operation was performed because of degenerative osteoarthritis. Cement-free implantation was performed in 209, cemented in 117 and hybrid implantation in 306 procedures. We were able to retrospectively review 442 (80.4%) of the patients (498 knees), for a follow-up time of 6 months to 10 years. The Knee Insall Rating Scale was improved from 60 points (34–70) preoperatively, to 92 points (74–100) postoperatively. The range of flexion at the latest follow-up was between 75 to 130 degrees (mean 98 degrees). Extension lag more than 10 degrees was found in 3 patients (0.68%). The radiological evaluation was performed according to Knee Society Röentgenographic Evaluation and Scoring System. Partial periprothetic radiolucent lines (<
1mm) were observed in 35 knees (7%), with no statistical significant difference between the three groups and no progression during the follow-up. No further clinical and radiological evidence of mechanical failure and no significant loss of the mechanical axis were noticed. There was a case of fatal pulmonary embolism, and a case of peroneal nerve palsy that fully recovered. Three knees were revised as a result of septic loosening.