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.

Mesenchymal stromal cells: properties and role in management of cutaneous diseases

“…Bone marrow has been the major source of MSCs for investigation and clinical use. Bone marrow stromal cells (BMSCs) are a heterogeneous cell population of multipotent skeletal stem cells, transit‐amplifying skeletal progenitors and bone marrow stromal fibroblasts . Their main functions are to provide nutrients and necessary growth factors to support the hematopoietic stem cells in the bone marrow, and differentiate into osteoblasts, chondroblasts, adipocytes and stromal fibroblasts .…”

“…Bone marrow stromal cells (BMSCs) are a heterogeneous cell population of multipotent skeletal stem cells, transit‐amplifying skeletal progenitors and bone marrow stromal fibroblasts . Their main functions are to provide nutrients and necessary growth factors to support the hematopoietic stem cells in the bone marrow, and differentiate into osteoblasts, chondroblasts, adipocytes and stromal fibroblasts . In the setting of the skin, particularly in wound healing, they are thought to be recruited to the area of inflammation to serve as transit‐amplifying progenitors, transdifferentiating into keratinocytes .…”

“…Furthermore, the lack of expression of co‐stimulatory molecules CD80, CD86 and CD40 make them tolerogenic with demonstrated T‐cell anergy to MSCs . They have also exhibited immune evasive measures to avoid natural killer (NK)‐induced lysis despite low expression of MHC class I molecules . However, up‐regulation of MHC class II expression in the presence of interferon (IFN)‐γ has been observed in vitro and development of BMSC‐specific memory T cells associated with rejection of an allogeneic stem cell graft has been reported in an in vivo murine model .…”

“…Mesenchymal stromal cells (MSCs) are non‐hematopoietic multipotent stromal cells that reside in and have been isolated from various sites of adult, perinatal and fetal tissues including the bone marrow, periosteum, adipose tissue, amniotic fluid, umbilical cord blood, umbilical cord Wharton's jelly, placenta and the skin; and based on the source of the cells, they have been given appropriate names (e.g. bone marrow stromal cells and adipose‐derived stromal cells).…”

“…bone marrow stromal cells and adipose‐derived stromal cells). However, due to their capability of differentiating into multiple mesenchymal lineage cells such as osteoblasts, chondrocytes, adipocytes, fibroblasts,and myoblasts, these stromal cells have also been more commonly called mesenchymal stromal cells . It is important to note that MSCs are a heterogeneous population of cells that have variable expression of markers depending on the tissue source and method of isolation, culture and cryopreservation; and in vitro expression of markers may not always reflect the expression patterns in vivo .…”