Mesenchymal stem cells (MSCs) protect tissues against cell death induced by ischemia/reperfusion insults. This therapeutic effect seems to be controlled by physiological cues released by the local microenvironment following injury. Recent lines of evidence indicate that MSC can communicate with their microenvironment through bidirectional exchanges of mitochondria. In particular, in vitro and in vivo studies report that MSCs rescue injured cells through delivery of their own mitochondria. However, the role of mitochondria conveyed from somatic cells to MSC remains unknown. By using a co-culture system consisting of MSC and distressed somatic cells such as cardiomyocytes or endothelial cells, we showed that mitochondria from suffering cells acted as danger-signaling organelles that triggered the anti-apoptotic function of MSC. We demonstrated that foreign somatic-derived mitochondria were engulfed and degraded by MSC, leading to induction of the cytoprotective enzyme heme oxygenase-1 (HO-1) and stimulation of mitochondrial biogenesis. As a result, the capacity of MSC to donate their mitochondria to injured cells to combat oxidative stress injury was enhanced. We found that similar mechanisms – activation of autophagy, HO-1 and mitochondrial biogenesis – occurred after exposure of MSC to exogenous mitochondria isolated from somatic cells, strengthening the idea that somatic mitochondria alert MSC of a danger situation and subsequently promote an adaptive reparative response. In addition, the cascade of events triggered by the transfer of somatic mitochondria into MSC was recapitulated in a model of myocardial infarction in vivo. Specifically, MSC engrafted into infarcted hearts of mice reduced damage, upregulated HO-1 and increased mitochondrial biogenesis, while inhibition of mitophagy or HO-1 failed to protect against cardiac apoptosis. In conclusion, our study reveals a new facet about the role of mitochondria released from dying cells as a key environmental cue that controls the cytoprotective function of MSC and opens novel avenues to improve the effectiveness of MSC-based therapies.
The aim of this study was to analyze the files of 695 consecutive patients operated on under general anesthesia for odontogenic cysts in an adult French teaching hospital for comparison with findings in world surveys. A retrospective survey of cysts of the jaws was undertaken at the Maxillofacial department, Pitié-Salpêtrière University Hospital, Paris, France. Data were retrieved from case notes, imaging, histopathology records and follow-up reports from January 1995 to January 2005. The mean age of patients was 41.8 +/- 15.8 years. There was an overall male to female ratio of 1.86:1. Mandible to maxilla ratio was 3:1. Regarding the mandible, the angle was involved in 36% of the cases, horizontal branch in 32%, parasymphysis in 18%, ramus in 11.6%, coronoid process in 1.5% and condyle in 0.9% (total = 100%). Regarding the maxilla, the canine to canine region was involved in 40% of the cases, premolar and molar region in 45%, and wisdom tooth region in 15% (total = 100%). The three most frequently diagnosed odontogenic cysts were radicular cysts (53.5%), dentigerous cysts (22.3%) and odontogenic keratocysts (19.1%). Together, these three entities represented 94.9% of all odontogenic cysts. The mean number of operation per patient was 1.16 (SD: 0.6, range: 1-10). The mean cumulated duration of hospitalization for one patient was 2.46 days (SD: 1.9, range: 1-28). The mean length of follow-up was 8.4 months (SD: 15.2, range: 0-120). Sixty five percent had a follow-up inferior to 6 months and 18% had no follow-up at all. The two most important findings of this case series are 1) the important number of radicular cysts that could be avoided because most of these cysts develop as a consequence of advanced carious lesions and 2) regarding other types of cysts, the dramatic rate of patients lost to follow-up.
Composite tissue allotransplantations can be indicated when autologous transfers fail to restore human appearance. We report the reproducibility, difficulties, serious adverse events and outcomes of our patients. Five patients were included in a registered clinical research protocol after thorough screenings assessed by an independent expert committee systematically discussing the alternative options. One patient suffered from plexiform neurofibromas, two from third degree burns and two from gunshot injuries.They were included on a national waiting list with a dedicated face procurement procedure. Transplants were harvested from heart beating brain-dead donors before other tissues and organs. Induction immunosuppressive therapy included antithymocyte globulins, steroids, mycophenolate mophetil and tacrolimus. Maintenance therapy included the last three ones associated with extracorporeal-photopheresis. Four patients were transplanted with 7-to 38-month followup. One could not due to multiple panel reactive antibodies after 18 months on waiting list. Acute cellular rejections were controlled by conventional treatment. Opportunistic infections affected all patients and lead one patient to die two month after the transplantation. Voluntary facial activity appeared from 3 to 5 month. Face transplantation has been reproducible under conventional immunosuppression. Major improvements in facial aesthetic and function allowed patients to recover social relations and improved their quality of life.
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