TAp63α Mediates Chemotherapeutic Agent-Induced Apoptosis in Human Bone Marrow Mesenchymal Stem Cells

Institute of Basic Medical Sciences and School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Stem cells and development (Impact Factor: 4.2). 12/2010; 20(8):1319-26. DOI: 10.1089/scd.2010.0329
Source: PubMed

ABSTRACT Human bone marrow-derived mesenchymal stem cells (MSCs) are currently widely used in cell therapy and tissue engineering. In vitro experiments have demonstrated that apoptosis of MSCs can be induced by hypoxia, serum deprivation, and chemotherapeutic agents, and the process is p53 independent. In this study, we investigated the role of p63 (a member of p53 family) in the regulation of apoptosis of MSCs. TAp63α, a subtype of p63, is highly similar to p53 and plays a crucial role in apoptosis. In vitro exposure of MSCs to either cisplatin or etoposide resulted in an increased TAp63α expression, which was time and dose dependent. Interference of TAp63α led to drug resistance and decreased apoptosis, accompanied by reduced expression of Bax, poly(ADP-ribose) polymerase, and caspase-3. However, downregulation of TAp63α did not influence the phenotype, proliferation capacity, and differentiation potential of MSCs. These results indicate that downregulation of TAp63α in MSCs is an attractive strategy to protect against apoptosis when MSCs are used to support hematopoiesis during bone marrow transplantation.

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    • "Chemotherapeutic agents induce TAp63 expression, which subsequently causes apoptosis by directly activating pro-apoptotic genes CD95, Bcl-2-family members such as bax and BCL2L11 as well as Apaf1 [55]. Consequently, inhibition of TAp63 function, which causes reduced apoptosis, leads to drug resistance in various cancers [55,58–60]. "
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