Bone marrow–derived mesenchymal stem cells (BMSCs) have been used for allogeneic application in tissue engineering but have certain drawbacks. Therefore, stem cells (SC)s derived from other adult tissue sources have been considered as an alternative. However, there is only limited knowledge on their immunomodulatory properties. The aim of our study was to compare the immunomodulatory potential of human amniotic mesenchymal and human amniotic epithelial cells with that of human adipose-derived SCs under identical experimental conditions. We have demonstrated a dose-dependent inhibition of peripheral blood mononuclear cell (PBMC) immune responses in mixed lymphocyte reactions (up to 66–93% inhibition) and phytohemagglutinin activation assays (up to 67–96% inhibition). The lowest SC-to-PBMC ratio able to inhibit PBMC proliferation significantly was 1:8. Subcultivation (passage 2–6) did not alter immunoinhibitory properties, whereas cryopreservation significantly reduced the immunomodulatory potential. Using transwell systems, we have demonstrated an inhibition mechanism that is dependent on cell contact. Additionally, in coculture with allogeneic PBMCs, SCs were well tolerated and at most provoked mild alloreactions in singular cases. This study demonstrates, for the first time, contact- and dose-dependent immunosuppression of mesenchymal and epithelial amniotic SC populations, as well as of adipose tissue–derived SCs. All three cell types may be considered as possible alternatives to BMSCs for allogeneic application in tissue engineering.

: Osteoporosis as a systemic skeletal disorder is characterized by increased bone fragility and the risk of fractures. According to the World Health Organization, osteoporosis is one of the 10 most common diseases and affects approximately 75 million people in Europe, the United States, and Japan. In this context, the identification of specific microRNA (miRNA) signatures is an important step for new diagnostic and therapeutic approaches. The focus of interest on miRNAs as biomarkers came with new publications identifying free circulating extracellular miRNAs associated with various types of cancer. This study aimed to identify specific miRNAs in patients with osteoporotic fractures compared with nonosteoporotic fractures. For the array analysis, miRNAs were isolated from the serum of 20 patients with hip fractures, transcribed, and the samples were pooled into 10 osteoporotic and 10 nonosteoporotic specimens. With each pool of samples, human serum and plasma miRNA PCR arrays were performed, which are able to identify 83 different miRNAs. Subsequently, a separate validation analysis of each miRNA found to be regulated in the array followed with miRNA samples isolated from the serum of 30 osteoporotic and 30 nonosteoporotic patients and miRNA samples isolated from the bone tissue of 20 osteoporotic and 20 nonosteoporotic patients. With the validation analysis of the regulated miRNAs, we identified 9 miRNAs, namely miR-21, miR-23a, miR-24, miR-93, miR-100, miR-122a, miR-124a, miR-125b, and miR-148a, that were significantly upregulated in the serum of patients with osteoporosis. In the bone tissue of osteoporotic patients, we identified that miR-21, miR-23a, miR-24, miR-25, miR-100, and miR-125b displayed a significantly higher expression. A total of 5 miRNAs display an upregulation both in serum and bone tissue. This study reveals an important role for several miRNAs in osteoporotic patients and suggested that they may be used as biomarkers for diagnostic purposes and may be a target for treating bone loss and optimizing fracture healing in osteoporotic patients. © 2014 American Society for Bone and Mineral Research.

The timing of definitive fixation for major fractures in patients with multiple injuries is controversial. To address this gap, we randomized patients with blunt multiple injuries to either initial definitive stabilization of the femur shaft with an intramedullary nail or an external fixateur with later conversion to an intermedullary nail and documented the postoperative clinical condition. Multiply injured patients with femoral shaft fractures were randomized to either initial (16 points, or 3 fractures and Abbreviated Injury Scale score ≥2 points and another injury (Abbreviated Injury Scale score ≥2 points), and age 18 to 65 years. Exclusion: patients in unstable or critical condition. Patients were graded as stable or borderline (increased risk of systemic complications). Incidence of acute lung injuries. Ten European Centers, 165 patients, mean age 32.7 ± 11.7 years. Group intramedullary nailing, n = 94; group external fixation, n = 71. Preoperatively, 121 patients were stable and 44 patients were in borderline condition. After adjusting for differences in initial injury severity between the 2 treatment groups, the odds of developing acute lung injury were 6.69 times greater in borderline patients who underwent intramedullary nailing in comparison with those who underwent external fixation, P < 0.05. Intramedullary stabilization of the femur fracture can affect the outcome in patients with multiple injuries. In stable patients, primary femoral nailing is associated with shorter ventilation time. In borderline patients, it is associated with a higher incidence of lung dysfunctions when compared with those who underwent external fixation and later conversion to intermedullary nail. Therefore, the preoperative condition should be when deciding on the type of initial fixation to perform in patients with multiple blunt injuries.

Damage control orthopedic surgery has recently been advocated for the management of femoral shaft fractures in severely injured patients because surgical procedures were found to represent a second-hit phenomenon regarding the operative burden. It has been attempted to determine the operative burden by means of proinflammatory cytokines. In this study in clinically stable patients with multiple injuries, the effects induced by different types of primary fracture stabilization on the systemic release of proinflammatory cytokines were evaluated. This was a prospective, randomized, multicenter intervention study. Inclusion criteria were long bone shaft fracture of the lower extremity; age 18 to 65 years; Injury Severity Score > 16 or more than three extremity injuries (Abbreviated Injury Scale [AIS] score of 2 or more) in association with another injury (AIS score of 2 or more); and thoracic AIS score < 4. After informed consent, randomization for the treatment of the femoral shaft fracture was performed at admission. Groups were as follows: group I°FN (primary, < 24 hours) intramedullary nailing, and group DCO (DCO, I°ex.fix.) damage control orthopedic surgery and external fixation. In DCO patients, measurements were also performed at the time of conversion to the intramedullary procedure (DCO II°FN). Parameters included clinical parameters and complications (acute respiratory distress syndrome, multiple organ failure, sepsis). From serially sampled central venous blood, the perioperative concentrations of interleukin IL-1, IL-6, and IL-8 were determined. Thirty-five patients were included (I°FN, n = 17; DCO, n = 18). In I°FN-patients, a perioperative increase of IL-6 levels was measured (preoperatively, 55 ± 33 pg/dL; 24 hours postoperatively, + 254 ± 55 pg/dL;p= 0.03), which was not found in subgroup DCO I°Ex.fix.: preoperatively, 71 ± 42 pg/dL; 24 hours postoperatively, 68 ± 34 pg/dL; not significant [NS] or in group DCO II°FN: preoperatively, 36 ± 21 pg/dL; 24 hours postoperatively, + 39 ± 25 pg/dL; NS. Likewise, in I°FN patients, a perioperative increase of IL-8 levels was measured only at the 7-hour time point (preoperatively, 35 ± 29 pg/dL; 7 hours postoperatively, 95 ± 23 pg/dL;p< 0.05), which was not found in group DCO I°Ex.fix.: preoperatively, 43 ± 38 pg/dL; 24 hours postoperatively, 69 ± 39 pg/dL; NS or in group DCO II°FN: preoperatively, 25 ± 20 pg/dL; 24 hours postoperatively, 36 ± 29 pg/dL; NS. There were no differences in the complication rate in terms of acute respiratory distress syndrome, sepsis, or multiple organ failure. In this prospective, randomized, multicenter study, a sustained inflammatory response was measured after primary (<24 hours) intramedullary femoral instrumentation, but not after initial external fixation or after secondary conversion to an intramedullary implant. These findings may become clinically relevant in patients at high risk of developing complications. It confirms previous studies in that damage control orthopedic surgery appears to minimize the additional surgical impact induced by acute stabilization of the femur.