RESUMO
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential stromal cells which are regarded as the most feasible stem cell group in cell therapy. The maintenance of cell survival without differentiation is important in cell transplantation and stem cell therapy. However, negative factors exist in cell transplantation. Lysophosphatidic acid (LPA) is a non-antigenic small molecule phospholipid which induced several fundamental cellular responses, such as cell proliferation, apoptosis and migration. In this study we aimed to explore the effects of LPA on the survival and differentiation of MSCs and its availability in cell therapy. We found that LPA stimulated hUC-MSC proliferation and protected hUC-MSCs from lipopolysaccharide (LPS) induced apoptosis. We also observed that CD29, CD44, CD73, CD90 and CD105 were expressed, whereas CD34 and CD45 were not expressed in hUC-MSCs, and these makers have no change in LPA containing medium, which indicated that LPA accelerated the survival of hUC-MSCs in an undifferentiating status. We also demonstrated that higher expressed LPAR1 involved in LPA stimulated cell survival action. LPA stimulated cell proliferation was associated with LPAR1 mediated Gi/o-proteins/ERK1/2 pathway. On the other hand, LPA protected hUC-MSCs from LPS-induced apoptosis through suppressing caspase-3 activation by LPAR1 coupled with a G protein, but not Gi/o or Gq/11 in hUC-MSC. Collectively, this study demonstrated that LPA increased the proliferation and survival of hUC-MSCs without differentiation through LPAR1 mediated manner. Our findings provide that LPA as a anti-apoptotic agent having potential application prospect in cell transplantation and stem cell therapy.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Lisofosfolipídeos/fisiologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Receptores de Ácidos Lisofosfatídicos/metabolismo , Cordão Umbilical/citologia , Antígenos de Diferenciação/genética , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Subunidades alfa de Proteínas de Ligação ao GTP/antagonistas & inibidores , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Lisofosfolipídeos/farmacologia , Sistema de Sinalização das MAP Quinases/fisiologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Receptores de Ácidos Lisofosfatídicos/antagonistas & inibidores , Receptores de Ácidos Lisofosfatídicos/genéticaRESUMO
Abstract: In this paper, Mitomycin C (MMC) was added to different kinds of medium to study the effects of different cultural conditions on the Erwinia herbicola 10025A. For the first time it was confirmed that the expressed activity of the ice-nuclei active protein was different from its transportable manner from the ice nucleation active bacteria (Erwinia herbicola 10025A). The findings indicated that MMC could stimulate the SOS response,and induce the synthesis of some enzymes and proteins, which take part in repairing the damaged DNA. The effects of the MMC on the E. herbicola under different media were different. It could increase the ice nucleation activity of the E. herbicola, forming new small vesicles, which are secreted to the outside of membrane. The importance of this research for study the living mechanism of cells ander poor condition was discussed.
