Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Patients with UDCA-Resistant Primary Biliary Cirrhosis

Abstract

The objective of this study was to evaluate the safety and efficacy of allogeneic bone marrow mesenchymal stromal/stem cell transplantation (BM-MSCT) for patients with ursodeoxycholic acid (UDCA)-resistant primary biliary cirrhosis (PBC). Ten patients were enrolled in this trial of BM-MSCT. All patients were permitted to concurrently continue their previous UDCA treatment. The efficacy of BM-MSCT in UDCA-resistant PBC was assessed at various time points throughout the 12-month follow up. No transplantation-related side effects were observed. The life quality of the patients was improved after BM-MSCT as demonstrated by responses to the PBC-40 questionnaire. Serum levels of ALT, AST, γ-GT, and IgM significantly decreased from baseline after BM-MSCT. In addition, the percentage of CD8+ T cells was reduced, while that of CD4+CD25+Foxp3+ T cells was increased in peripheral lymphocytic subsets. Serum levels of IL-10 were also elevated. Notably, the optimal therapeutic outcome was acquired in 3 to 6 months and could be maintained for 12 months after BM-MSCT. In conclusion, allogeneic BM-MSCT in UDCA-resistant PBC is safe and appears to be effective.

Status of and candidates for cell therapy in liver cirrhosis: overcoming the “point of no return” in advanced liver cirrhosis

“…MSCs can be obtained from not only bone marrow but also medical wastes such as adipose tissue [57,58], umbilical tissue [59][60][61][62], and dental pulp [63]. MSCs are positive for the common markers CD73, CD90, and CD105; however, they are negative for the endothelial marker CD31 and hematopoietic marker CD45 [56,64].…”

“…In the field of liver cirrhosis, as shown in Table 1, many autologous [70][71][72][73][74][75][76][77][78][79][80][81][82][83] and four allogeneic [59][60][61][62] MSC therapies involving a variety of tissue origins and administration routes have been reported. Although details regarding the mechanisms of therapeutic effects in humans remain unclear, most studies have reported favorable effects with improvement in MELD scores, Child-Pugh scores, and some serum markers such as albumin and bilirubin.…”

Recent advances in the diagnosis and treatment of primary biliary cholangitis

“…Mesenchymal stem cell (MSC) transplantation is considered to be safe, and has been diffusely tested in autoimmune hepatic disease clinical trials with encouraging results[186,187]. MSC transplantation could modulate the systemic immune response and promote recovery in hepatic inflammation of PBC[186,187].…”

Stem cell transplantation for the treatment of liver diseases: A systematic review and meta-analysis

“…Of these retrieved studies, 202 were excluded because of animal experiments, reviews, or insufficiently detailed data. Overall, we identified and included 17 publications involving 20 studies that met the inclusion criteria (11,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). There were five papers that involved two studies.…”