ABSTRACT
BACKGROUND: Mesenchymal stromal cells (MSCs) are a promising candidate for treatment of inflammatory disorders, but their efficacy in human inflammatory bowel diseases (IBDs) has been inconsistent. Comparing the results from various pre-clinical and clinical IBD studies is also challenging due to a large variation in study designs. METHODS: In this comparative pre-clinical study, we compared two administration routes and investigated the safety and feasibility of both fresh and cryopreserved platelet-lysate-expanded human bone marrow-derived MSCs without additional licensing in a dextran sodium sulfate (DSS) colitis mouse model both in the acute and regenerative phases of colitis. Body weight, macroscopic score for inflammation and colonic interleukin (IL)-1ß and tumor necrosis factor (TNF)α concentrations were determined in both phases of colitis. Additionally, histopathology was assessed and Il-1ß and Agtr1a messenger RNA (mRNA) levels and angiotensin-converting enzyme (ACE) protein levels were measured in the colon in the regenerative phase of colitis. RESULTS: Intravenously administered MSCs exhibited modest anti-inflammatory capacity in the acute phase of colitis by reducing IL-1ß protein levels in the inflamed colon. There were no clear improvements in mice treated with fresh or cryopreserved unlicensed MSCs according to weight monitoring results, histopathology and macroscopic score results. Pro-inflammatory ACE protein expression and shedding were reduced by cryopreserved MSCs in the colon. CONCLUSIONS: In conclusion, we observed a good safety profile for bone marrow-derived platelet lysate-expanded MSCs in a mouse pre-clinical colitis model, but the therapeutic effect of MSCs prepared without additional licensing (i.e. such as MSCs are administered in graft-versus-host disease) was modest in the chosen in vivo model system and limited to biochemical improvements in cytokines without a clear benefit in histopathology or body weight development.
Subject(s)
Blood Platelets/metabolism , Colitis/therapy , Cryopreservation , Inflammatory Bowel Diseases/therapy , Mesenchymal Stem Cell Transplantation/adverse effects , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/metabolism , Animals , Cells, Cultured , Colitis/chemically induced , Dextran Sulfate/pharmacology , Disease Models, Animal , Feasibility Studies , Follow-Up Studies , Humans , Injections, Intraperitoneal/methods , Injections, Intravenous/methods , Interleukin-1beta/metabolism , Male , Mice , Mice, Inbred BALB C , Treatment Outcome , Tumor Necrosis Factor-alpha/metabolismABSTRACT
A prospective, randomized study comparing the compression hip screw with the Gamma nail in the treatment of 426 intertrochanteric fractures is reported. The median patient age was 80 years, and 71% were women The compression hip screw operation took less time except in Evans Type 5 fractures. Blood loss generally was less in the compression hip screw group except in patients with Type 5 fractures. The most frequent surgical problem for patients in the Gamma group was problems with distal locking. Cephalic position of the femoral head screw and cut-out were seen more often in the Gamma nail group. The Gamma nail more frequently preserved the fracture position obtained perioperatively. Whether there was distal locking of the Gamma nail in unstable fractures did not seem to affect the healing rate. Additional fissures or fractures in the proximal femur occurred during five Gamma nail operations and two compression hip screw operations. Postoperative walking ability did not differ between the groups. At 6 months 88% of the fractures were healed. In less comminuted fractures, the compression hip screw method is the preferred method of treatment whereas the Gamma nail is an alternative treatment for more comminuted Evans Type 5 fractures.