Apoptosis in stem cell therapy

Background: Multipotent mesenchymal stromal cells (MSCs) are fibroblastic precursor cells that have the stem cell-like ability to differentiate into a variety of cell types. MSCs isolated from the bone marrow are endowed with anti-inflammatory and tissue reparative properties, and are being investigated in clinical trials to treat various inflammatory conditions. It is generally thought that MSCs secrete soluble factors that dampen inflammation and repair damaged tissue. We recently challenged this dogma (Pang et al., 2021, Nature Communications). We found that MSCs infused into the blood undergo cell death and are rapidly engulfed by macrophages and cleared from the body. Our data indicate a pivotal role for macrophages in MSC therapy, but it remains unclear how macrophages are reprogrammed by MSCs to become anti-inflammatory. Project aim/s: This project aims to elucidate how the innate and adaptive immune responses to viable and dying MSCs impact therapeutic efficacy. The findings will have broad implications for the future development of MSC-based therapies. Techniques: This project will utilise techniques applicable to both immunology and stem cell research, including stem and immune cell isolation, tissue culture, flow cytometry, immunoassays, stem cell differentiation, fluorescence microscopy, in vivo disease models. Reference: Pang SHM, D’Rozario J, Mendonca S, Bhuvan T, Payne NL, Zheng D, Barugahare A, Powell D, Rautela J, Huntington N, Dewson G, Huang DCS, Gray DHD, Heng TSP (2021). Mesenchymal stromal cell apoptosis is required for their therapeutic function. Nature Communications 12, 6495. doi: 10.1038/s41467-021-26834-3.