Journal Article

The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy

Krasnodembskaya, Anna, Hawthorne, Ian J., Isaza-Correa, Johana M., Mahon, Bernard P., Weiss, Daniel J., English, Karen

2019

Overview

Rapid progress is occurring in understanding the mechanisms underlying mesenchymal stromal cell (MSC)-based cell therapies (MSCT). However, the results of clinical trials, while demonstrating safety, have been varied in regard to efficacy. Recent data from different groups have shown profound and significant influences of the host inflammatory environment on MSCs delivered systemically or through organ-specific routes, for example intratracheal, with subsequent actions on potential MSC efficacies. Intriguingly in some models, it appears that dead or dying cells or subcellular particles derived from them, may contribute to therapeutic efficacy, at least in some circumstances. Thus, the broad cellular changes that accompany MSC death, autophagy, pre-apoptotic function, or indeed the host response to these processes may be essential to therapeutic efficacy. In this review, we summarize the existing literature concerning the necrobiology of MSCs and the available evidence that MSCs undergo autophagy, apoptosis, transfer mitochondria, or release subcellular particles with effector function in pathologic or inflammatory environments. Advances in understanding the role of immune effector cells in cell therapy, especially macrophages, suggest that the reprogramming of immunity associated with MSCT has a weighty influence on therapeutic efficacy. If correct, these data suggest novel approaches to enhancing the beneficial actions of MSCs that will vary with the inflammatory nature of different disease targets and may influence the choice between autologous or allogeneic or even xenogeneic cells as therapeutics.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Animals / Apoptosis / Asthma / Autophagy / Biological Transport / Bone marrow / Cell Communication - immunology / Cell death / Cell therapy / Cell- and Tissue-Based Therapy - adverse effects / Cell- and Tissue-Based Therapy - methods / Clinical trials / Effector cells / extracellular vesicles / Extracellular Vesicles - metabolism / Humans / Immunology / Inflammation / Injuries / Lung diseases / Macrophages / Macrophages - immunology / Macrophages - metabolism / Mesenchymal Stem Cell Transplantation - adverse effects / Mesenchymal Stem Cell Transplantation - methods / Mesenchymal stem cells / Mesenchymal Stem Cells - metabolism / mesenchymal stromal cell / mitochondria / Mitochondria - metabolism / Sepsis / Stromal cells / Trachea / Treatment Outcome