Artículos de revistas
Hepatogenic and neurogenic differentiation of bone marrow mesenchymal stem cells from abattoir-derived bovine fetuses
Fecha
2014-07-10Registro en:
BMC Veterinary Research 2014, 10:154
1746-6148
DOI: 10.1186/1746-6148-10-154
Autor
Dueñas, Fernando
Becerra Ivanovic, Víctor Ignacio
Cortés Araya, Yennifer Alejandra
Vidal Vilches, Sonia
Sáenz Iturriaga, Leonardo Enrique
Palomino Mackenney, Jaime
Reyes Solovera, Mónica de los
Peralta Troncoso, Óscar
Institución
Resumen
Background: Mesenchymal stem cells (MSC) are multipotent progenitor cells characterized by their ability to both
self-renew and differentiate into tissues of mesodermal origin. The plasticity or transdifferentiation potential of
MSC is not limited to mesodermal derivatives, since under appropriate cell culture conditions and stimulation by
bioactive factors, MSC have also been differentiated into endodermal (hepatocytes) and neuroectodermal (neurons)
cells. The potential of MSC for hepatogenic and neurogenic differentiation has been well documented in different
animal models; however, few reports are currently available on large animal models. In the present study we sought to
characterize the hepatogenic and neurogenic differentiation and multipotent potential of bovine MSC (bMSC) isolated
from bone marrow (BM) of abattoir-derived fetuses.
Results: Plastic-adherent bMSC isolated from fetal BM maintained a fibroblast-like morphology under monolayer
culture conditions. Flow cytometric analysis demonstrated that bMSC populations were positive for MSC markers
CD29 and CD73 and pluripotency markers OCT4 and NANOG; whereas, were negative for hematopoietic markers CD34
and CD45. Levels of mRNA of hepatic genes α-fetoprotein (AFP), albumin (ALB), alpha1 antitrypsin (α1AT), connexin 32
(CNX32), tyrosine aminotransferase (TAT) and cytochrome P450 (CYP3A4) were up-regulated in bMSC during a 28-Day
period of hepatogenic differentiation. Functional analyses in differentiated bMSC cultures evidenced an increase (P < 0.05)
in albumin and urea production and glycogen storage. bMSC cultured under neurogenic conditions expressed NESTIN
and MAP2 proteins at 24 h of culture; whereas, at 144 h also expressed TRKA and PrPC. Levels of MAP2 and TRKA mRNA
were up-regulated at the end of the differentiation period. Conversely, bMSC expressed lower levels of NANOG mRNA
during both hepatogenic and neurogenic differentiation processes.
Conclusion: The expression patterns of linage-specific markers and the production of functional metabolites support the
potential for hepatogenic and neurogenic differentiation of bMSC isolated from BM of abattoir-derived fetuses.
The simplicity of isolation and the potential to differentiate into a wide variety of cell lineages lays the foundation for
bMSC as an interesting alternative for investigation in MSC biology and eventual applications for regenerative therapy in
veterinary medicine.