Trends Mol Med. Author manuscript; available in PMC 2010 June 8.
Published in final edited form as:
PMCID: PMC2881950
NIHMSID: NIHMS202644
Department of Medicine, Brigham and Womens Hospital, Harvard Medical School, Harvard Stem Cell Institute, Harvard-MIT Division of Health Sciences and Technology 65 Landsdowne Street, Cambridge, MA 02139, USA
Corresponding author: Karp, J.M. (Email: jkarp/at/rics.bwh.harvard.edu)
Mesenchymal stem cell (MSC) therapy is poised to establish a new clinical paradigm; however, recent trials have produced mixed results. Although MSC were originally considered to treat connective tissue defects, preclinical studies revealed potent immunomodulatory properties that prompted the use of MSC to treat numerous inflammatory conditions. Unfortunately, although clinical trials have met safety endpoints, efficacy has not been demonstrated. We believe the challenge to demonstrate efficacy can be attributed in part to an incomplete understanding of the fate of MSC following infusion. Here, we highlight the clinical status of MSC therapy and discuss the importance of cell-tracking techniques, which have advanced our understanding of the fate and function of systemically infused MSC and might improve clinical application.
Imagine a simple intravenous cell therapy that can restore function to damaged or diseased tissue, avoid host rejection and reduce inflammation throughout the body without the use of immunosuppressive drugs. Such a breakthrough would revolutionize medicine. Fortunately, pending regulatory approval, this approach might not be far off. Specifically, cell therapy utilizing adult mesenchymal stem cells (MSC, Box 1), multipotent cells with the capacity to promote angiogenesis, differentiate to produce multiple types of connective tissue and downregulate an inflammatory response, are the focus of a multitude of clinical studies currently underway. MSC are being explored to regenerate damaged tissue and treat inflammation, resulting from cardiovascular disease and myocardial infarction (MI), brain and spinal cord injury, stroke, diabetes, cartilage and bone injury, Crohns disease and graft versus host disease (GvHD) [1]. The problems, however, are that some recent late stage clinical trials have failed to meet primary endpoints, and the fate of MSC following systemic infusion as well as the mechanisms through which they impact host biology are largely unknown [2].
Although they have donned many names, i.e. mesenchymal stem cells, mesenchymal stromal cells, multipotent stromal cells, marrow stromal cells and colony-forming unit-fibroblastic, MSCs were originally described as adherent cells from bone marrow that form colonies [42]. Later these cells were found to have multilineage differentiation potential because they could form connective tissue cell types capable of producing bone, adipose and cartilage [43].The International Society for Cellular Therapy (ISCT) defines human MSCs as tissue- culture plastic adherent cells capable of osteogenesis, adipogenesis and chondrogenesis that are positive for CD73, CD90 and CD105 but negative for CD11b, CD14, CD34, CD45, CD79a and HLA-DR surface markers [44]. Despite these guidelines, characterizing and defining the MSC phenotype represents an ongoing challenge [2,45,46]. Bone marrow-derived MSCs are a heterogeneous population of cells and MSC characteristics such as surface marker expression, proliferation rate and differentiation potential are dependent on passage, cell density and the cell culture media [46]. The discovery of MSCs in fat and virtually all other mature tissues [47] has introduced additional nuances in that MSC properties seem to depend on the tissue from which they are isolated [46]. Although MSCs were initially considered for therapy based on their multilineage differentiation capacity, their ability to secrete cytokines and growth factors that are antiapoptotic, proangiogenic and have the potential to reduce scarring and inflammation have positioned MSCs for a broader spectrum of clinical applications [48]. In particular, the use of MSCs to downregulate inflammation offers significant therapeutic potential for treating inflammatory diseases. Specifically, MSCs possess the ability to reduce B-cell proliferation, monocyte maturation and secretion of interferon- and TNF- while promoting T-regulatory cell induction and secretion of IL-10 [39,40]. presents a summary of MSC traits and properties.
Reported MSC characteristics
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