Distinctively, Evercyte has a readily available array of human cells from different organs and tissues, including skin fibroblasts, lung fibroblasts, umbilical vein endothelial cells, podocytes, microvascular endothelial cells, keratinocytes, kidney epithelial cells, mesenchymal stem cells, etc., that enable rapid specific screening of a wide range of different compounds.
Accumulation of senescent cells in vivo
Senescent cells are damaged cells that are not performing their ‘normal’ activities, commonly called ‘zombie cells’ that accumulate in tissues and interfere with normal cellular functioning. These cells are associated with several diseases and seem to contribute to different pathologies. Removing senescent cells is of extreme importance to improve prognosis and is one of the current challenges in the life sciences.
Recent studies have also shown that senescence plays a role in tumor biology in both positive and negative ways. It appears that induction of senescence during premalignancy or as an early response to chemotherapy might stall tumor progression through its tumor suppressive mechanism. However, if senescent cells are not appropriately cleared by the immune system and persist in these settings after the chemotherapy treatment, they can promote further tumor growth and relapse. Therefore, the idea of first inducing senescence by chemotherapeutics, followed by clearance of such senescent cells, the ‘1-2-punch strategy’, has also provided promising results in pre-clinical cancer models.
Induction of senescence in tumor cells
Evercyte offers several options for induction of senescence in human cells in vitro: one is in vitro propagation until cells enter replicative senescence after a defined number of population doublings (growth until replicative senescence).
Another option is to treat normal human cells with the chemotherapy drug doxorubicin following established protocols to raise stress-induced premature senescence (SIPS) levels.
SIPS cells as well as replicative senescent cells can be used to test customer derived compounds for a potential senolytic / senomorphic activity in multi-well plate format using different read-outs for measuring the activity of the compounds on the cells.
Establishment of in vitro bioassays to test 1-2 punch strategy
Besides testing cellular viability and characterization of the cellular morphology, expression of SA-ß-galactosidase, marker gene transcription (p16, p21, etc.), analysis of cell cycle progression / BrdU incorporation, or analysis of senescence-associated secretory phenotype (expression or secretion of MCP1, Il6, IL8and of miRNAs´) can be used to get insights into the biological activity of the testing compounds on senescent cells.
Evercyte also offers services to establish assay-ready tumor cell lines upon customer request for testing the potency of drugs to induce senescence in tumor cells. Arising senescent cells are subsequently killed off by senolytic drugs following the 1-2 punch strategy.
Senolytic testing service benefits
Customer derived samples are handled by experienced cell biologists with more than 25 years’ experience with normal/telomerized cells, tumor cells, senescence, and characterization of senescent phenotype, cell viability and cell death mechanisms.
The Evercyte senolytic and senomorphic testing service offers a range of tangible benefits including:
- Enables direct senolytic comparison of different drugs
- Ready availability of all techniques, cells and reagents required for rapid senolytic characterization of any chosen drug
- Excellent data quality assured
- Fast process using pre-established techniques, with all assays performed promptly upon request.
Click on Evercyte senolytic/senomorphic drug testing services for further information.
Click on Evercyte assay-ready cell establishment for further information.
Click on Evercyte drug screening services for further information.
Click on The efficacy of chemotherapy is limited by intratumoural senescent cells that persist through the upregulation of PD-L2 for background on relationship between chemotherapies and senolytics.
Click on Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic for related research study.