Mesenchymal stem cells (MSCs) are currently defined as multipotent stromal cells that undergo sustained in vitro growth and can give rise to cells of multiple mesenchymal lineages, such as adipocytes, chondrocytes, and osteoblasts. The regenerative and immunosuppressive properties of MSCs have led to numerous clinical trials exploring their utility for the treatment of a variety of diseases (e.g., acute graft-versus-host disease, Crohn’s disease, multiple sclerosis, osteoarthritis, and cardiovascular diseases including heart failure and myocardial infarction). On the other hand, conventionally cultured MSCs reflect heterogeneous populations that often contain contaminating cells due to the significant variability in isolation methods and the lack of specific MSC markers. This review article focuses on recent developments in the MSC research field, with a special emphasis on the identification of novel surface markers for the in vivo localization and prospective isolation of murine and human MSCs. Furthermore, we discuss the physiological importance of MSC subtypes in vivo with specific reference to data supporting their contribution to HSC niche homeostasis. The isolation of MSCs using selective markers (combination of PDGFRα and Sca-1) is crucial to address the many unanswered questions pertaining to these cells and has the potential to enhance their therapeutic potential enormously. 1. Introduction Bone marrow (BM) is comprised of hematopoietic stem cell (HSC) and nonHSC populations. Mesenchymal stem cells (MSCs) reside in the nonHSC fraction. HSCs form the cornerstone of therapy for many hematological diseases. MSCs, on the other hand, are nonhematopoietic cells initially identified in the BM [1–4] that can differentiate along various mesenchymal lineages to generate fat, bone, and cartilage. The hypothesized physiological function of MSCs is to support hematopoiesis and stromal tissue regeneration. Interestingly, these multipotent cells are found in a variety of fetal and adult tissues in addition to the BM, including umbilical cord blood [5, 6], dental pulp [7, 8], term placenta [9, 10], and adipose tissue [11, 12]. MSCs possess therapeutic potential for the repair and regeneration of damaged tissues of mesenchymal origin [13, 14]. Additionally, they have potent immunosuppressive properties and are currently utilized to treat a wide variety of autoimmune conditions [15–19]. Despite the large number of clinical studies now investigating the suitability of MSCs as therapeutic agents, conventional adherence to a plastic tissue culture substrate is
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