Senescence in adipose-derived stem cells and its implications in nerve regeneration

Adult mesenchymal stem cells, specifically adipose-derived stem cells have self-renewal and multiple differentiation potentials and have shown to be the ideal candidate for therapeutic applications in regenerative medicine, particularly in peripheral nerve regeneration. Adipose-de- rived stem cells are easily harvested, although they may show the effects of aging, hence their potential in nerve repair may be limited by cellular senescence or donor age. Cellular senescence is a complex process whereby stem cells grow old as consequence of intrinsic events （e.g., DNA damage） or environmental cues （e.g., stressful stimuli or diseases）, which determine a permanent growth arrest. Several mechanisms are implicated in stem cell senescence, although no one is exclusive of the others. In this review we report some of the most important factors modulating the senescence process, which can influence adipose-derived stem cell morphology and function, and compromise their clinical application for peripheral nerve regenerative cell therapy.

免疫疗法联合立体定向放疗治疗非小细胞肺癌脑转移:一项AIRO多中心回顾性研究

背景与目的 通过意大利放射治疗和临床肿瘤学学会(Italian Association of Radiotherapy and Clinical Oncology, AIRO)的一项多中心回顾性研究,明确免疫疗法(immunotherapy, IT)和立体定向放疗(stereotactic radiotherapy,SRT)包括放射外科治疗(radiosurgery, RS)或大分割立体定向放疗(hypofractionated stereotactic radiotherapy, HFSRT)治疗非小细胞肺癌(non-small cell lung cancer, NSCLC)脑转移的疗效和毒性。方法 对来自19个意大利中心接受SRT+IT的NSCLC伴脑转移患者进行分析,并与单独接受SRT的对照组患者进行比较。结果 共纳入SRT+IT组100例和单独SRT组50例。接受SRT+IT的患者有更长的颅内局部无进展生存期(intracranial local progression-free survival, i LPFS)(经倾向性评分调整后,P=0.007)。在诊断为脑转移时接受IT合并有颅外进展的患者中(n=24),接受SRT后再进行IT与较好的总生存期(overall survival, OS)相关(P=0.037)。多因素分析显示组织学类型为非腺癌、卡氏体能状态(Karnofsky performance status,KPS)评分=70分以及接受HFSRT与显著减少的生存期相关(P值分别为0.019、0.017和0.007)。与SRT和IT治疗间隔>7天(n=10)相比,治疗间隔≤7天(n=90)与更长的OS相关(经倾向性评分调整后,P=0.008)。联合治疗耐受性良好。在放射性坏死方面,接受SRT+IT的患者与单独SRT的患者无显著差异。SRT和IT的治疗间隔对毒性发生率无影响。结论 SRT+IT是一种安全的联合治疗方法,与单独SRT相比,具有更长的i LPFS。