p38 Mitogen-activated protein kinase modulates exocrine secretion in rabbit lacrimal gland

Carlsson, Stina K.; Gierow, J. Peter

doi:10.2478/s11658-011-0031-y

Cited by 1 publication

(1 citation statement)

References 18 publications

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“…Thus, it might be worthwhile thinking whether a combination of hepatocytes and MSC might be the cell therapeutic of best choice. Indeed, there is evidence that the performance of hepatocytes is improved in co-culture with MSC (Ijima et al, 2008 ; Shi et al, 2009 ; Chen et al, 2012 ), and vice versa MSC differentiation into hepatocyte-like cells is promoted by inflammatory liver injury conditions (Dong et al, 2010 ; Li et al, 2010 ). Recent data even demonstrated that not MSC themselves but as yet unequivocally unidentified soluble factors secreted by MSC exert the beneficial effects on hepatocytes under ALF conditions in mice and rats (Parekkadan et al, 2007b ; van Poll et al, 2008 ; Zagoura et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Rodent Animal Models for Surrogate Analysis of Cell Therapy in Acute Liver Failure

Christ¹,

Brückner²

2012

Front. Physio.

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Without therapeutic intervention acute liver failure (ALF) is the consequence of a progredient destruction of the liver parenchyma due to metabolic exhaustion of the hepatocytes. Perivenous hepatocytes are responsible for the detoxification of noxious compounds via the cytochrome P450 enzyme system. Liver transplantation is the only remaining therapeutic option in the end-stage of the disease. Assuming that metabolic capacity could be provided by healthy hepatocytes and thus substitute for the genuine parenchymal cells hepatocyte transplantation since quite some time is considered to be an alternative to whole liver transplantation. While this hypothesis achieved proof-of-concept in animal trials clinical breakthrough is still awaiting success, the reasons of which are ongoing matter of debate. In recent times mesenchymal stem cells (MSC) came into focus as a transplantable cell source to treat ALF. Interestingly, as demonstrated in various rodent animal models their mode of action is rather based on trophic support of hepatocytes remaining in the damaged host parenchyma rather than substitution of tissue loss. Mechanistically, either direct or indirect paracrine effects from the transplanted cells acting pro-proliferative, anti-apoptotic, and anti-inflammatory seem to trigger the regenerative response of the residual healthy hepatocytes in the otherwise lethally injured liver parenchyma. Thus, allogeneic MSC may be the best choice for the treatment of ALF taking advantage of their short-term benefit to sustain the critical phase of the acute insult avoiding long-term immunosuppression.

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