Beyond the horizon: the newly found sinner disturbing mesenchymal stromal niche.

Hematopoietic stem-cell transplantation (HSCT) is an important, potentially curative therapeutic option for hema-tological malignancies. However, poor and slow hematopoi- etic reconstitution remains a significant complication, which is correlated with abnormal hematopoietic stem-cell (HSC) func- tion. The maintenance and the preservation of HSC functional properties are supported by a highly specialized microenviron- ment within the bone marrow (BM), in which BM-derived mesenchymal stem cells (BMSCs) serve as the essential structural and functional basis for constituting the BM microenviron-ment. Damage, such as that due to chemotherapy, radiother- apy or inflammation, delays hematopoietic recovery or causes hematopoiesis dysfunction or failure, seriously affecting HSCT efficacy. 1 The key to remodeling and repairing the BM micro-environment lies in the repair of the niche structure by cellular therapies which include BMSCs. Research has increasingly confirmed that the most crucial functions of BMSCs are to main- tain the turnover of the BM stroma and skeletal tissues and to provide critical hematopoietic support. 2 However, the underly-ing mechanisms that regulate these different functions are not well known. In the recent BLOOD publication, the Dr. Zhao and Dr. Jiang group revealed that the retinoic acid-inducible gene I (RIG-I) plays a substantial role in regulating the stromal niche for hematopoietic reconstitution. 3 All-trans retinoic acid (ATRA) and inflammation stress upregulated RIG-I expres- sion, thus damaging the clonogenicity, the bone-forming ability of BMSCs and the supporting function in the stromal niche; mechanistically, this is achieved by suppressing the antioxidant impact of nuclear