Reply.

Abstract

Firstly, thank you very much for the valuable suggestions on our article. Our reply is as follows. In our preliminary experiment, we divided patients into three groups, 10 patients in each group. Group A received standard medicine treatment (SMT) only. Group B was treated with allogeneic bone marrow‐derived mesenchymal stem cells (BM‐MSCs) every week for 4 weeks, at a dosage of 1 × 105/kg. For group C the dosage of BM‐MSCs was 10 × 106/kg. No significant difference was found in the levels of liver function and 24‐week survival rate between groups B and C (data not published). This may be related to the peripheral vein infusion. Therefore, in our formal study we did not conduct a subgroup analysis. In our study, we infused BM‐MSCs through the peripheral vein for the following reasons. (1) Systemic inflammatory reactions play a key role in the development of acute‐on‐chronic liver failure (ACLF).(1) BM‐MSCs regulate immunity through paracrine mechanisms.(2) (2) ACLF patients have coagulation disorders, and infusion of BM‐MSCs through the hepatic artery has a risk of hemorrhage. Therefore, we speculated that intravenous infusion might be a better delivery method for ACLF patients. Lastly, the best source of MSCs is unclear. Some studies have shown that bone marrow has better proliferative potential.(3) Recently, a pooled analysis showed that “bone marrow‐derived MSCs are optimal in terms of improving liver function.”(4) We considered that a large‐scale, randomized, controlled trial is still needed to compare the efficacy between BM‐MSCs and umbilical cord–derived MSCs for ACLF patients. A comprehensive assessment is needed to study the benefits of these two sources of MSCs for ACLF patients. Thanks again for your valuable suggestions. Potential conflict of interest Nothing to report.