Acute Genotoxic Stress-Induced Senescence in Human Mesenchymal Cells Drives a Unique Composition of Senescence Messaging Secretome (SMS)

نویسندگان

  • Meenakshi Gaur
  • Lu Wang
  • Alexandra Amaro-Ortiz
  • Marek Dobke
چکیده

MSC mediate numerous therapeutic effects by promoting repair directly via differentiation into critical cell types or indirectly through the secretion of a broad spectrum of soluble factors with diverse paracrine activities. However, recent discoveries indicate that MSC are sensitive to endogenous and exogenous stressors and many diseaserelated interventions can result in Therapy-Induced Senescence (TIS) in MSC. Here, we provide a detailed analysis of changes in secretory factors that occur under conditions of bleomycin treatment that triggers genotoxic stressinduced senescence of Human Adipose-Derived Stem Cells (hADSCs). The bleomycin treatment considerably alters the composition of hADSCs secretome. Our data reveal the novel unique composition of Senescence Messaging Secretome (SMS) of hADSCs and suggest that this SMS might critically influence genotoxic drug-based or MSC combinational therapies by imposing interference with tissue homeostasis, metabolism and regeneration in autocrine and paracrine fashion. SMS can compromise MSC-mediated immunological responses and their regenerative potential. Our findings underscore the importance of careful evaluation of stress-induced senescence of adult stem cells in regenerative and combination therapies. Acute Genotoxic Stress-Induced Senescence in Human Mesenchymal Cells Drives a Unique Composition of Senescence Messaging Secretome (SMS) Meenakshi Gaur1, Lu Wang2, Alexandra Amaro-Ortiz1, Marek Dobke3, I. King Jordan2,4 and Victoria V Lunyak1* 1Aelan Cell Technologies, San Francisco, CA 2School of Biology, Georgia Institute of Technology, Atlanta, GA 3Division of Plastic Surgery, University of California, San Diego, La Jolla, California 4PanAmerican Bioinformatics Institute, Cali, Valle del Cauca, Colombia *Corresponding author: Victor ia V Lunyak, Aelan Cel l Technologies, San Francisco, CA 94107, USA, Tel : +1(619) 306-1700; E-mai l : [email protected] Received July 20, 2017; Accepted August 14, 2017; Published August 20, 2017 Citation: Gaur M, Wang L, Amaro-Ortiz A, Dobke M, King Jordan I, et al. (2017) Acute Genotoxic Stress-Induced Senescence in Human Mesenchymal Cells Drives a Unique Composition of Senescence Messaging Secretome (SMS). J Stem Cell Res Ther 7: 396. doi: 10.4172/2157-7633.1000396 Copyright: © 2017 Gaur M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses

Senescent cells secrete senescence-associated secretory phenotype (SASP) proteins to carry out several functions, such as sensitizing surrounding cells to senesce; immunomodulation; impairing or fostering cancer growth; and promoting tissue development. Identifying secreted factors that achieve such tasks is a challenging issue since the profile of secreted proteins depends on genotoxic stress ...

متن کامل

Myeloma cells can corrupt senescent mesenchymal stromal cells and impair their anti-tumor activity

Senescent cells secrete several molecules that help to prevent the progression of cancer. However, cancer cells can also misuse these secreted elements to survive and grow. Since the molecular and functional bases of these different elements remain poorly understood, we analyzed the effect of senescent mesenchymal stromal cell (MSC) secretome on the biology of ARH-77 myeloma cells. In addition ...

متن کامل

Effects of alpha-mangostin on memory senescence induced by high glucose in human umbilical vein endothelial cells

Objective(s): Hyperglycemia induces cellular senescence in various body cells, such as vascular endothelial cells. Since the vessels are highly distributed in the body and nourish all tissues, vascular damages cause diabetes complications such as kidney failure and visual impairment. Alpha-mangostin is a xanthone found in mangosteen fruit with protective effects in met...

متن کامل

In Vitro Evaluation of Protective Effect of Rutin on Acrylamide-Induced Cellular Senescence in NIH3T3 Cells

Background: Aging is one of the important factors in the development of age-related diseases. Acrylamide can be produced during carbohydrate-rich foods prepared at high temperatures. Recently, studies showed that acrylamide can induce cellular senescence. On the other hand, Rutin as a natural flavonoid, has a potent antioxidant activity. Objective: This study aims to evaluate the ptotective ef...

متن کامل

The Lcn2-engineered HEK-293 cells show senescence under stressful condition

Objective(s): Lipocalin2 (Lcn2) gene is highly expressed in response to various types of cellular stresses. The precise role of Lcn2 has not been fully understood yet. However, it plays a key role in controlling vital cellular processes such as proliferation, apoptosis and metabolism. Recently it was shown that Lcn2 decreases senescence and increases proliferation of mesenchymal stem cells (MSC...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2017