However, the same studies indicate that this subset is limited to differentiation into skeletal cell types found at different developmental stages as well as at specific anatomical sites. PLoS One 6(5):e19808, Hall SR, Tsoyi K, Ith B, Padera RF Jr et al (2013) Mesenchymal stromal cells improve survival during sepsis in the absence of heme oxygenase-1: the importance of neutrophils.

Immunol Lett 89(2–3):267–270, Vogel W, Grunebach F, Messam CA et al (2003) Heterogeneity among human bone marrow-derived mesenchymal stem cells and neural progenitor cells. -Occurs when one cell divides to generate two identical stem cells.

The history of the biology of Mesenchymal Stem Cells (MSCs) owes it conception and birth to the earlier discovery of its more illustrious bone marrow (BM) resident sibling—the hematopoietic stem cell (HSC), whose existence was first proposed by Maximov in 1909. J Orthop Res 9(5):641–650, Zuk PA, Zhu M, Ashjian P et al (2002) Human adipose tissue is a source of multipotent stem cells. Stem Cells Transl Med 1(6):510–519, Bruder SP, Jaiswal N, Ricalton NS et al (1998) Mesenchymal stem cells in osteobiology and applied bone regeneration. Enter your email address below and we will send you your username, If the address matches an existing account you will receive an email with instructions to retrieve your username, Drug and Cell-Based Therapy Development, Manufacturing and Regulations, Tissue Engineering and Regenerative Medicine, I have read and accept the Wiley Online Library Terms and Conditions of Use, Characterization of cells with osteogenic potential from human marrow, Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement, Selling stem cells in the USA: Assessing the direct‐to‐consumer industry, Mechanisms involved in the therapeutic properties of mesenchymal stem cells, Mesenchymal stem cells as trophic mediators, Multipotent mesenchymal stromal cells and the innate immune system, Adult mesenchymal stem cells: When, where, and how, 3‐acetylpyridine: Effects in vitro related to teratogenic activity in chicken embryos, Interrelationship between poly (ADP‐Rib) synthesis, intracellular NAD levels, and muscle or cartilage differentiation from mesodermal cells of embryonic chick limb, The control of muscle and cartilage development in the chick limb: The role of differential vascularization, First bone formation in the developing chick limb, Characterization of a bone‐specific alkaline phosphatase in chick limb mesenchymal cell cultures, Control of chondrogenic expression in mesodermal cells of embryonic chick limb, Nicotinamide adenine dinucleotide levels in cells of developing chick limbs: Possible control of muscle and cartilage development, The development of embryonic bone and cartilage in tissue culture, The histogenesis of cartilage and bone in the long bones of the embryonic fowl, Immunohistochemical localization of short chain cartilage collagen (type X) in avian tissues, Environmental regulation of type X collagen production by cultures of limb mesenchyme, mesectoderm, and sternal chondrocytes, Isolation and characterization of proteoglycans from chick limb bud chondrocytes grown in vitro, Biosynthesis of proteoglycans by chick limb bud chondrocytes, Isolation and preliminary characterization of proteoglycans synthesized by skeletal muscle, Proteoglycans produced by skeletal muscle in vitro and in vivo, Solubilized and insolubilized bone morphogenetic protein, A fraction from extracts of demineralized adult bone stimulates the conversion of mesenchymal cells into chondrocytes, The in vitro chondrogenic response of limb‐bud mesenchyme to a water‐soluble fraction prepared from demineralized bone matrix, Novel regulators of bone formation: Molecular clones and activities, Identification of transforming growth factor beta family members present in bone‐inductive protein purified from bovine bone, Role of morphogenetic proteins in skeletal tissue engineering and regeneration, Biochemical sequences in the transformation of normal fibroblasts in adolescent rats, The origins of bone marrow as the seedbed of our blood: From antiquity to the time of Osler, Development of an osteogenic bone‐marrow preparation, Heterotopic of bone marrow.

Stem Cells Dev 17(5):929–940, Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, Krause U et al (2005) Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Nat Commun 2:499, Krautler NJ, Kana V, Kranich J et al (2012) Follicular dendritic cells emerge from ubiquitous perivascular precursors. Nat Biotechnol 25(12):1468–1475, Nagoshi N, Shibata S, Nakamura M et al (2009) Neural crest-derived stem cells display a wide variety of characteristics.

In human BM, MCAM marks adventitial reticular cells (, The assumed existence of a homogeneous stromal stem cell population present in multiple mesenchyme-derived tissues remains open to question. These observations further support the concept that all pMSCs have both MSC‐common and MSC‐unique chemical and functional features. Thus, the melanoma must pass through the endothelial cell layer, its basal lamina or basement membrane and past the dense covering of mural cells.

Dev Cell 20(6):815–826, Ceradini DJ, Kulkarni AR, Callaghan MJ et al (2004) Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. At such disease sites, the MSC rarely or never differentiate into the tissue at that site 13, 88, but they secrete bioactive factors (some of the names of these factors we know 94) and their therapeutic effects can be analyzed as site‐specific clinical outcome parameters. Proc Natl Acad Sci USA 97(25):13625–13630, Nakamura S et al (2009) Stem cell proliferation pathways comparison between human exfoliated deciduous teeth and dental pulp stem cells by gene expression profile from promising dental pulp.

J Vasc Res 36(1):2–27, Vrancken Peeters MP, Gittenberger-de Groot AC, Mentink MM, Poelmann RE (1999) Smooth muscle cells and fibroblasts of the coronary arteries derive from epithelial–mesenchymal transformation of the epicardium.

In fact, most aspects of the biology of perivascular MSCs are still obscure, from the emergence of these cells in the embryo to the molecular control of their activity in adult tissues.

Correspondence to Circulation 109(12):1543–1549, Gnecchi M, He H, Liang OD et al (2005) Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Restor Neurol Neurosci 30(1):55–68, Kuci S, Kuci Z, Kreyenberg H et al (2010) CD271 antigen defines a subset of multipotent stromal cells with immunosuppressive and lymphohematopoietic engraftment-promoting properties. Orthod Craniofac Res 8(3):191–199, Schuring AN et al (2011) Characterization of endometrial mesenchymal stem-like cells obtained by endometrial biopsy during routine diagnostics.

Non-invasive Reporter Gene Imaging of Cell Therapies, including T Cells and Stem Cells. is commonplace, this claim is not rooted in equally solid experimental evidence with heterotopic transplantation of the progeny of a single cell and thus remains controversial. Because the function of MSCs in vivo is secretory and primarily functional at sites of injury, disease, or inflammation, I now favor this terminology 12. J Orthop Res 28(12):1634–1642, Lazarus HM, Haynesworth SE, Gerson SL et al (1997) Human bone marrow-derived mesenchymal (stromal) progenitor cells (MPCs) cannot be recovered from peripheral blood progenitor cell collections. Unfortunately, the fact that MSCs are called “stem cells” is being used to infer that patients will receive direct medical benefit, because they imagine that these cells will differentiate into regenerating tissue‐producing cells. Several protocols were recently established to enable regeneration of large bone defects by using human MSCs (hMSCs) that have been expanded in culture. This new knowledge paved the way for the widespread adoption of BM transplantation in lymphoproliferative disease where aggressive antitumor ablation with irradiation and chemotherapy, followed by transplantation with healthy HSCs from tissue-compatible donors, could rescue the marrow [44]. Exp Cell Res 317(20):2950–2957, Torsvik A, Rosland GV, Svendsen A et al (2010) Spontaneous malignant transformation of human mesenchymal stem cells reflects cross-contamination: putting the research field on track—letter. Tissue Cell 18(2):153–174, Diaz-Flores L, Martin Herrera AI, Garcia Montelongo R et al (1990) Role of pericytes and endothelial cells in tissue repair and related pathological processes. Ultimately, it would be desirable that the function, the assay, and the phenotype all be traced back to an anatomically recognizable cell type in situ. Stem Cells 25(1):220–227, Daquinag AC, Zhang Y, Amaya-Manzanares F et al (2011) An isoform of decorin is a resistin receptor on the surface of adipose progenitor cells. Although the hypothesis was firmly established, and the supporting experimental evidence was published and widely reproduced, the concept of a nonhematopoietic stem cell in BM did not resonate worldwide until additional similar work was published in 1999 (, Questions have been raised over the usage of the term “mesenchymal stem cells” (, Nonetheless, the term has gained such global usage that it would perhaps be futile to suggest replacing it with another that would better adhere to the known biology of the system.

J Tissue Eng Regen Med 5:589–599, Muller AM, Mehrkens A, Schafer DJ et al (2010) Towards an intraoperative engineering of osteogenic and vasculogenic grafts from the stromal vascular fraction of human adipose tissue.

Am J Sports Med 39(7):1401–1412, Khojasteh A, Behnia H, Dashti SG et al (2012) Current trends in mesenchymal stem cell application in bone augmentation: a review of the literature. Maria P. Alfaro, ... Pampee P. Young, in Vitamins & Hormones, 2011.

Sci Transl Med 4(141):141ra93, Marquass B, Schulz R, Hepp P et al (2011) Matrix-associated implantation of predifferentiated mesenchymal stem cells versus articular chondrocytes: in vivo results of cartilage repair after 1 year. One implication of this trait is that, although one can purchase commercial cultures of MSCs, they are more accurately described as cultures of BMSCs and may or may not include a proportion of multipotent and self-renewing cells. Since the implant was walled‐off, encysted by a layer of these mesenchymal cells comparable to the stack cell layer of the embryonic chick tibia, all blood vessels were excluded. Paulo Bianco and Pamela Robey [51] later proposed putative pericyte/reticular cell topography of MSCs in the BM.

Application of MSCs requires their isolation and directing the differentiation of these cells into the appropriate lineage. One is the classically recognized function of providing a supportive microenvironment for hematopoiesis. Biochem Biophys Res Commun 288(2):413–419, Kulterer B, Friedl G, Jandrositz A et al (2007) Gene expression profiling of human mesenchymal stem cells derived from bone marrow during expansion and osteoblast differentiation. Furthermore, whereas the original notion of MSCs specifically referred to cells in BM (bone marrow stromal cells, BMSCs), the current notion has been extended to include cells from additional sources (such as synovium, adipose tissue, dental pulp, etc.) Cell 129(7):1377–1388, LaBonne C, Bronner-Fraser M (1999) Molecular mechanisms of neural crest formation.

Stem Cells Dev. Fertil Steril 95(1):423–426, Spitzer TL et al (2012) Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype. Development 129(11):2773–2783, Mendes SC, Robin C, Dzierzak E (2005) Mesenchymal progenitor cells localize within hematopoietic sites throughout ontogeny.

J Cell Biochem 112(4):1206–1218, Avanzini MA, Bernardo ME, Cometa AM et al (2009) Generation of mesenchymal stromal cells in the presence of platelet lysate: a phenotypic and functional comparison of umbilical cord blood- and bone marrow-derived progenitors. Nanoengineering in Musculoskeletal Regeneration. Journal of ISAKOS: Joint Disorders & Orthopaedic Sports Medicine.

These invading vessels brought a fresh supply of mesenchymal progenitor cells, which then formed vascularized and marrowized bone. The best known source of MSCs in adult humans is the bone marrow (BM) compartment; this region contains several types of cells, including those of the hematopoietic lineage as well as endothelial cells (ECs) and MSCs that are part of the marrow stromal system (Pittenger et al., 1999). Again, for emphasis, these MSC‐effects are medicinal.

2008 Sep 11;3(3):301-13. doi: 10.1016/j.stem.2008.07.003. Frontiers in Cell and Developmental Biology. Thus, the infusion of hMSCs in an osteoarthritic knee is imagined to contribute directly into the regeneration of cartilage tissue by the infused MSCs forming functional chondrocytes that fabricate functional cartilage tissue.

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