Short and long term fate of human AMSC subcutaneously injected in mice

AIM:To study the ability of human adipose-derived mesenchymal stem cells(AMSCs)to survive over the short and long term,their biodistribution and their biosafety in vivo in tumor-prone environments.METHODS:We subcutaneously injected human AMSCs from different human donors into immunodeficient SCID mice over both short-(2 and 4 mo)and long-(17 mo)term in young,and aged tumor-prone mice.Presence of human cells was studied by immunohistochemistry and polymerase chain reaction analysis in all organs of injected mice.RESULTS:Subcutaneously injected AMSCs did not form teratomas at any time point.They did not migrate but remained at the site of injection regardless of animal age,and did not fuse with host cells in any organ examined.AMSCs survived in vivo for at least 17 mo after injection,and differentiated into fibroblasts of the subdermic connective tissue and into mature adipocytes of fat tissue,exclusively at the site of injection.CONCLUSION:Our results support the assertion that AMSC may be safe candidates for therapy when injected subcutaneously because of their long term inability to form teratomas.

Splanchnic-aortic inflammatory axis in experimental portal hypertension

Splanchnic and systemic low-grade inflammation has been proposed to be a consequence of long-term prehepatic portal hypertension.This experimental model causes minimal alternations in the liver,thus making a more selective study possible for the pathological changes characteristic of prehepatic portal hypertension.Low-grade splanchnic inflammation after longterm triple partial portal vein ligation could be associated with liver steatosis and portal hypertensive intestinal vasculopathy.In fact,we have previously shown that prehepatic portal hypertension in the rat induces liver steatosis and changes in lipid and carbohydrate metabolism similar to those produced in chronic inflammatory conditions described in metabolic syndrome in humans.Dysbiosis and bacterial translocation in this experimental model suggest the existence of a portal hypertensive intestinal microbiome implicated in both the splanchnic and systemic alterations related to prehepatic portal hypertension.Among the systemic impairments,aortopathy characterized by oxidative stress,increased levels of proinflammatory cytokines and profibrogenic mediators stand out.In this experimental model of long-term triple portal vein ligated-rats,the abdominal aortic proinflammatory response could be attributed to oxidative stress.Thus,the increased aortic reduced-nicotinamide-adenine dinucleotide phosphate[NAD(P)H]oxidase activity could be associated with reactive oxygen species production and promote aortic inflammation.Also,oxidative stress mediated by NAD(P)H oxidase has been associated with risk factors for inflammation and atherosclerosis.The splanchnic and systemic pathology that is produced in the long term after triple partial portal vein ligation in the rat reinforces the validity of this experimental model to study the chronic low-grade inflammatory response induced by prehepatic portal hypertension.