Potential of mesenchymal stem cells as immune therapy in solid-organ transplantation (original) (raw)

2009, Transplant International

What is already known? Characteristics of MSCs Over the last decade, various medical disciplines have become increasingly interested in mesenchymal stem cells (MSCs), whose unique characteristics are potentially useful for clinical therapy. MSCs are present in most tissues, including bone marrow, adipose tissue, skin, placenta and heart [1-5], and can be isolated and expanded ex vivo. They are selected on the basis of their capacity to adhere to plastic, and are characterized by their fibroblast-like morphology in culture, immunophenotype and multilineage differentiation capacity [1,2]. As no specific marker for MSCs has been found yet, MSCs are identified by a panel of cell-surface markers, including CD29, CD44, CD73 (SH3/4), CD90 (Thy-1), CD105 (SH2), CD106 (VCAM-1), CD166 (ALCAM) and HLA class-I. MSCs do not express hematopoietic or endothelial lineage markers such as CD11b, CD14, CD31, CD34, or CD45 [1,6,7]. Also, unless they are stimulated with IFN-c, MSCs do not express the co-stimulatory molecules CD80 and CD86 or HLA class-II [8,9]. One of the main functional properties of MSCs is their capacity to differentiate into a variety of specialized cell types, such as osteoblasts, chondrocytes, adipocytes, myocytes (Fig. 1) or neuronal precursors cells [1,10,11]. This capacity makes them promising candidates for use in regenerative medicine. Human and animal studies have shown that MSCs have potential to repair bone [12,13], cartilage [14,15], skin [16,17], and neuronal tissue [18] and improve the function of cardiac muscle [19-21] and the kidney [22]. Recent clinical trials are investigating the use of MSCs in treating heart disease, liver cirrhosis and bone fractures. It is unclear whether MSCs contribute to tissue repair by differentiation into tissue-specific cell types, or whether they produce trophic factors at the site of injury, which either stimulate tissue-repair [23,24] or which conceivably reduce self-inflicting damage by the immune system. In addition to their capacity for multilineage