Model of Liver Fibrosis Induction by Thioacetamide in Rats for Regenerative Therapy Studies.

Hepatic fibrosis is caused by chronic injury due to toxic, infectious, or metabolic causes, and it may progress to cirrhosis and hepatocellular carcinoma. There is currently no antifibrotic therapy authorized for human use; however, there are promising studies using cell therapies. There are also no animal models that exactly reproduce human liver fibrosis that can be used to better understand the mechanisms of its regression and identify new targets for treatment and therapeutic approaches. On the other hand, mesenchymal stem cells (MSC) have experimentally demonstrated fibrosis regression effects, but it is necessary to have an animal model of advanced liver fibrosis to evaluate the effect of these cells. The aim of this work was to establish a protocol for the induction of advanced liver fibrosis in rats using thioacetamide (TAA), which will allow us to perform trials using MSC as a possible therapy for fibrosis regression. For this purpose, we selected 24 female rats and grouped them into three experimental groups: the control group (G-I) without treatment and groups II (G-II) and III (G-III) that received TAA by intraperitoneal injection for 24 weeks. Then, 1 × 106/kg adipose mesenchymal stem cells (ASCs) were infused intravenously. Groups G-I and G-II were sacrificed 7 days after the last dose of ASC, and G-III was sacrificed 8 weeks after the last ASC infusion, all with xylazine/ketamine (40 mg/kg). The protocol used in this work established a model of advanced hepatic fibrosis as corroborated by METAVIR tests of the histological lesions; by the high levels of the markers α-SMA, CD68, and collagen type I; by functional alterations due to elevated markers of the hepatic lesions; and by alterations of the leukocytes, lymphocytes, and platelets. Finally, transplanted cells in the fibrous liver were detected. We conclude that TAA applied using the protocol introduced in this study induces a good model of advanced liver fibrosis in rats.

Multidose intramuscular allogeneic adipose stem cells decrease the severity of canine atopic dermatitis: A pilot study.

AIM: The aim of this pilot study was to evaluate the therapeutic and safety performance of an intramuscular treatment protocol of multidose of allogeneic adipose stem cells (ASCs) isolated, characterized, and expanded ex vivo from a healthy canine donor. MATERIALS AND METHODS: Twelve dogs diagnosed with canine atopic dermatitis (CAD) were intramuscularly treated with 0.5×106 of cryopreserved ASCs from a healthy immunized young canine Ehrlichia canis free donor weekly for 6 weeks. Treatment efficacy was evaluated by the pruritus index and the CAD Lesion Index (CADLI) test. Safety and adverse effects were determined by injection site reaction, weight, blood chemistry, liver function, and whole blood count. RESULTS: Canine ASCs obtained from a donor met the minimum qualities required for this type of cells and showed viability of 90% after thawing. The efficacy of the CADLI score and the pruritus index in 12 dogs with atopic dermatitis was statistically significant efficacy. No adverse reactions were observed at the intramuscular application site, or in relation to animal weight, blood cell populations, or liver and renal function. CONCLUSION: These results suggest that intramuscular administration of cryopreserved ASCs to dogs with atopic dermatitis is a promising cellular therapeutic product for the relief of the symptoms of this disease; however, the duration of the effects obtained with this dose and with other doses should be evaluated, as well as possible immune reactions. As far as we know, this is the first report of the use of multiple intramuscular doses cryopreserved ASCs to treat atopic dermatitis.