Bone marrow stromal cells as immunomodulators. A primer for dermatologists

Abstract

Bone marrow stromal cells (BMSCs, also known as mesenchymal stem cells or MSCs) represent a unique cell population in the bone marrow with a long-known function to support hematopoiesis and replace skeletal tissues. The recent discovery that BMSCs also possess potent immunoregulatory features attracted a great deal of attention from stem cell biologists, immunologists and clinicians of different specialties worldwide. Initial clinical experience along with several animal models suggested that intravenously delivered BMSCs are able to regulate a wide variety of host immune cells and act in a way that is beneficial for the recipient in a variety of diseases. The role of the present review is to give a short introduction to the biology of BMSCs and to summarize our current understanding of how BMSCs modulate the immune system with special emphasis on available clinical data. Considering the audience of this journal we will also attempt to guide dermatologists in choosing the right skin conditions where BMSCs might be considered as a therapeutic alternative.

Keywords: Bone marrow stromal cells; Immunomodulation; Inflammatory; Mesenchymal stem cells; Skin conditions.

Fig 1

Stem cell populations of the bone marrow and the progenies of skeletal stem cells are shown along with a summary of the most important characteristics of BMSCs. (The chondorgenic differentiation picture is a gift of Dr. Matthew Phillips) During in vitro culturing the default cell type (labeled with pink background) is the skeletal fibroblast, which are the cells used in the clinical settings. Using specific media, the transit-amplifying progenitors can be differentiated towards osteogenic, adipogenic or chondrogenic lineage (blue background).

Fig 2

Immunoregulation by BMSCs. BMSCs secrete several soluble factors (PGE2, NO, IDO etc.) that together can trigger generation of regulatory T cells and anti-inflammatory M2 monocytes/macrophages. In concert with these cells BMSCs can suppress the differentiation of antigen presenting dendritic cells as well as the functions of helper T cells, B cells, NK cells, and mast cells. By secreting IL-6 BMSCs can also prevent apoptosis of neutrophil granulocytes thereby supporting their antibacterial functions.