Myocardial infarctions and chronic ischemic heart disease both commonly and disproportionately affect elderly patients more than any other patient population. Despite available treatments, heart tissue is often permanently damaged as a result of cardiac injury. This review aims to summarize recent literature proposing the use of modified autologous adult stem cells to promote healing of post-infarct cardiac tissue. This novel cellular treatment involves isolation of adult stem cells from the patient, in vitro manipulation of these stem cells, and subsequent transplantation back into the patient’s own heart to accelerate healing. One of the hindrances affecting this process is that cardiac issues are increasingly common in elderly patients, and stem cells recovered from their tissues tend to be pre-senescent or already in senescence. As a result, harsh in vitro manipulations can cause the aged stem cells to undergo massive in vivo apoptosis after transplantation. The consensus in literature is that inhibition or reversal of senescence onset in adult stem cells would be of utmost benefit. In fact, it is believed that this strategy may lower stem cell mortality and coerce aged stem cells into adopting more resilient phenotypes similar to that of their younger counterparts. This review will discuss a selection of the most efficient and most-recent strategies used experimentally to enhance the effectiveness of current stem cell therapies for ischemic heart diseases.
Autologous human cardiac stem/progenitor cell (hCPC) therapy is a promising treatment that has come into use in recent years for patients with cardiomyopathy. Though innovative in theory, a major hindrance to the practical application of this treatment is that the hCPCs of elderly patients, who are most susceptible to myocardial disease, are senescent and prone to cell death. Rejuvenating hCPCs from elderly patients may help overcome this obstacle, and can be accomplished by reversing entry into the cellular stage of senescence. p16, a cyclin dependent kinase inhibitor, is an important player in the regulation of cell senescence. In this study, we investigated whether knockdown of p16 will rejuvenate aging hCPCs to a youthful phenotype. Our data indicated that upregulation of p16 is associated with hCPC senescence. Both cell proliferation and survival capacity were significantly increased in hCPCs infected with lentivirus expressing p16 shRNA when compared to control hCPCs. The knockdown of p16 also induced antioxidant properties as indicated by a 50% decrease in ROS generation at basal cell metabolism, and a 25% decrease in ROS generation after exposure to oxidative stress. Genes associated with cell senescence (p21), anti-apoptosis (BCL2 and MCL1), anti-oxidant (CYGB, PRDX1 and SRXN1), and NFκB signal pathway (p65, IKBKB, HMOX1, etc.), were significantly upregulated after the p16 knockdown. Knocking down the NFĸB-p65 expression also significantly diminished the cytoprotective effect caused by the p16 knockdown. Our results suggest that genetic knockdown of p16 may play a significant role in inducing antioxidant effects and extending lifespan of aging hCPCs. This genetic modification may enhance the effectiveness of autologous hCPC therapy for repair of infarcted myocardium.
Background The endoscopic endonasal approach (EEA) has become increasingly used for resection of skull base tumors in the sellar and suprasellar regions. A nasoseptal flap (NSF) is routinely used for anterior skull base reconstruction; however, there are numerous additional allografts and autografts being used in conjunction with the NSF. The role of perioperative cerebrospinal fluid (CSF) diversion is also unclear.
Objective This study was aimed to analyze success of high-flow CSF leak repair during EEA procedures without use of CSF diversion through lumbar drainage.
Methods A retrospective chart review of patients who had intraoperative high-flow CSF leak during EEA procedures at our institution between January 2013 and December 2017 was performed. CSF leaks were repaired with use of a fascia lata button graft and nasoseptal flap, without use of perioperative lumbar drains.
Results A total of 38 patients were identified (10 male, 28 female). Patient BMIs ranged from 19.7 to 49 kg/m2 (median = 31 kg/m2), with 18 patients meeting criteria for obesity (BMI > 30 kg/m2) and 12 patients overweight (25 kg/m2 < BMI < 29.9 kg/m2). There was no incidence of postoperative CSF leak.
Conclusion In our experience, the nasoseptal flap used in conjunction with the fascia lata button graft is a safe, effective and robust combination for cranial base reconstruction with high-flow intraoperative CSF leaks, without need for lumbar drains.
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