These results suggest that the transplanted cells did not engraft in the liver and were eliminated from the rats.

Cord blood is an attractive cell source in regenerative medicine and represents an alternative to bone marrow. The aim of this study was to investigate whether human umbilical cord blood mononuclear (HUCBM) cells might be valuable in hepatic regenerative medicine. HUCBM cells differentiated in vitro into hepatocytes, as suggested by expression of albumin, cytokeratin-18, glutamine synthetase, α-fetoprotein, and cytochrome P450 3A4 at both mRNA and protein levels in a time-dependent fashion. In contrast, the hematopoietic phenotype was gradually lost, as demonstrated by disappearance of CD45 expression. The regenerative potential of HUCBM cells was tested by using a human-to-rat xenotransplant model in which HUCBM cells were intraportally injected into rats with D-galactosamine-induced hepatitis. Liver histology and biochemical markers of hepatic damage were determined. Presence of human cells was detected in blood and liver of both control and D-galactosamine-treated animals. Cell transplantation produced an improvement in both the histological damage and liver function, as demonstrated by plasma values of alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, and total and direct bilirubins. Results obtained suggest that HUCBM cells are capable of hepatic engraftment in this human-to-rat xenotransplant model and that transplantation of HUCBM cells may be a suitable therapy for liver disease.

Our research group investigates whether human mononuclear cells isolated from umbilical cord blood (HUCBM cells) might be valuable in hepatic regenerative medicine. We recently demonstrated that HUCBM cell transplantation improves histological alterations and function of the liver in rats with acute liver damage induced by D-galactosamine. In the present study, HUCBM cells were transplanted into rats with thioacetamide (TAA)-induced liver cirrhosis, an experimental model that generates an intense fibrosis and mimics the histological and biochemical alterations found in the human disease. HUCBM transplantation had no effect on hepatic histology of cirrhotic animals. In contrast, analysis of plasma albumin and total bilirubin, liver damage markers, revealed a harmful effect of HUCBM cell transplantation in our experimental model of liver cirrhosis. Significantly higher plasma urea concentrations, marker of renal function, were observed in the cirrhotic and control rats intraportally injected with HUCBM cells than in those not receiving this therapy. Histological study revealed tubular and glomerular lesions in kidneys of cirrhotic animals transplanted with HUCBM cells. The glomeruli appeared ischemic, and the tubules showed a severe involvement that included peripheral asymmetric vacuolization and disappearance of the tubular lumen. Taken together, the histological and biochemical data suggest that the cirrhotic rats subjected to HUCBM cell therapy developed a hepatorenal syndrome.Key words: Cell transplantation; Fibrosis; Human mononuclear cells; Liver cirrhosis; Thioacetamide; Umbilical cord blood INTRODUCTIONcurrently being investigated in regenerative medicine of the liver, and numerous groups have studied the transplantation of hepatocytes in experimental models of Liver diseases affect approximately 17% of the world population and entail high social costs (11). Whole liver liver disease (8,14). Similar experiments have been performed in humans in various countries, with encouragtransplantation, the current therapy for end-stage hepatic disease, is limited by the shortage of organ donors (20).ing results (3,5,19). Hematopoietic stem cells from bone marrow (BMSC) Furthermore, there is no specific treatment for the liver fibrosis that develops in chronic hepatic diseases, reor umbilical cord blood (UCBSC) are also being tested for this purpose. BMSC gave rise to functional hepatogardless of their etiology (22). Accordingly, novel therapies are required to alleviate the suffering of many pacytes in the liver of mice with tyrosinemia (9), and UCBSC produced similar results in mice with liver damage due tients.Cell transplantation represents one new therapeutic to overexpression of Fas ligand (13 (17,18), and were found to improve human liver funcwhereas the control group (n = 46) received water for the same time period (4,16). tion in noncontrolled and nonrandomized phase I clinical trials (6,21).Transplantation Experiments Our research group investigates whether human mononuclear cells isolated from umbilical c...

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Obesity has reached pandemia levels and is becoming a serious health problem in industrialized countries. Intestinal microbiota is considered a main factor of body weight and fat mass, which points toward a critical role in the development of obesity and its complications. The effects of Lactobacillus (L.) paracasei CNCM I-4034 feeding on the immune system and glucidic metabolism in a genetic model of obesity were investigated. Obese and lean Zucker rats were used. Animals received orally either 10 10 CFU of L. paracasei CNCM I-4034 or a placebo for 1 month. After the intervention period samples of serum, intestinal mucosa and feces were taken. Parameters related with glycidic metabolism and inflammation markers were measured in the serum. A differential gene expression (DNA array) study and a histological evaluation were carried out in the intestinal samples. Total IgA content was quantified in the faeces. No alteration compared with regular intestinal histology was observed in the mucosa or any other layer of the ileum or colon in any of the experimental groups, which suggests that the probiotic did not alter the morphology of this organ. Nor did serum glucose, insulin, leptin and adiponectin concentrations change. Expression of 45 intestinal genes was affected by feeding with the probiotic strain. Serum concentrations of CCL2, MIP-1a, IL-2 and IL-18 increased in obese rats fed L. paracasei CNCM I-4034. In contrast, IL-6 concentration decreased. A greater content of total IgA was found in the feces of the rats that received the probiotic strain. Our results suggest that L. paracasei CNCM I-4034 stimulated the immune response in the intestine of obese rats, which could be beneficial to defeat infections.