Mesenchymal Stem Cells: Time to Change the Name!

Mesenchymal stem cells (MSCs) were officially named more than 25 years ago to represent a class of cells from human and mammalian bone marrow and periosteum that could be isolated and expanded in culture while maintaining their in vitro capacity to be induced to form a variety of mesodermal phenotypes and tissues. The in vitro capacity to form bone, cartilage, fat, etc., became an assay for identifying this class of multipotent cells and around which several companies were formed in the 1990s to medically exploit the regenerative capabilities of MSCs. Today, there are hundreds of clinics and hundreds of clinical trials using human MSCs with very few, if any, focusing on the in vitro multipotential capacities of these cells. 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. Such a stem cell treatment will presumably cure the patient of their medically relevant difficulties ranging from osteoarthritic (bone‐on‐bone) knees to various neurological maladies including dementia. I now urge that we change the name of MSCs to Medicinal Signaling Cells to more accurately reflect the fact that these cells home in on sites of injury or disease and secrete bioactive factors that are immunomodulatory and trophic (regenerative) meaning that these cells make therapeutic drugs in situ that are medicinal. It is, indeed, the patient's own site‐specific and tissue‐specific resident stem cells that construct the new tissue as stimulated by the bioactive factors secreted by the exogenously supplied MSCs. Stem Cells Translational Medicine 2017;6:1445–1451

[1]  E. Masliah,et al.  Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo. , 2017, Cell stem cell.

[2]  M. Crisan,et al.  Pericytes, integral components of adult hematopoietic stem cell niches , 2017, Pharmacology & therapeutics.

[3]  J. Spinazzola,et al.  Exosomal Small Talk Carries Strong Messages from Muscle Stem Cells. , 2017, Cell stem cell.

[4]  T. Malta,et al.  The gene expression profile of non-cultured, highly purified human adipose tissue pericytes: Transcriptomic evidence that pericytes are stem cells in human adipose tissue. , 2016, Experimental Cell Research.

[5]  P. Knoepfler,et al.  Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry. , 2016, Cell stem cell.

[6]  W. Schiemann,et al.  Mesenchymal stem cells regulate melanoma cancer cells extravasation to bone and liver at their perivascular niche , 2016, International journal of cancer.

[7]  Z. Han,et al.  Proangiogenic Features of Mesenchymal Stem Cells and Their Therapeutic Applications , 2016, Stem cells international.

[8]  A. Caplan Adult Mesenchymal Stem Cells: When, Where, and How , 2015, Stem cells international.

[9]  T. Malta,et al.  Cultured Human Adipose Tissue Pericytes and Mesenchymal Stromal Cells Display a Very Similar Gene Expression Profile. , 2015, Stem cells and development.

[10]  J. Cuenca,et al.  Characterization of menstrual stem cells: angiogenic effect, migration and hematopoietic stem cell support in comparison with bone marrow mesenchymal stem cells , 2015, Stem Cell Research & Therapy.

[11]  D. Phinney,et al.  Mesenchymal stem cells as cellular vectors for pediatric neurological disorders , 2014, Brain Research.

[12]  F. Figueroa,et al.  The Promising Potential of Menstrual Stem Cells for Antenatal Diagnosis and Cell Therapy , 2014, Front. Immunol..

[13]  I. Herman,et al.  Pericyte-endothelial crosstalk: implications and opportunities for advanced cellular therapies. , 2014, Translational research : the journal of laboratory and clinical medicine.

[14]  A. Caplan,et al.  Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine , 2013, Experimental & Molecular Medicine.

[15]  A. Bergman,et al.  Arteriolar niches maintain haematopoietic stem cell quiescence , 2013, Nature.

[16]  D. Mougiakakos,et al.  Multipotent mesenchymal stromal cells and the innate immune system , 2012, Nature Reviews Immunology.

[17]  N. S. Asli,et al.  Adult cardiac-resident MSC-like stem cells with a proepicardial origin. , 2011, Cell stem cell.

[18]  V. Bautch,et al.  Stem cells and the vasculature , 2011, Nature Medicine.

[19]  Arnold I Caplan,et al.  The MSC: an injury drugstore. , 2011, Cell stem cell.

[20]  B. Cooper The Origins of Bone Marrow as the Seedbed of Our Blood: From Antiquity to the Time of Osler , 2011, Proceedings.

[21]  Jerome Ritz,et al.  The elusive nature and function of mesenchymal stem cells , 2011, Nature Reviews Molecular Cell Biology.

[22]  M. Matthay,et al.  Antibacterial Effect of Human Mesenchymal Stem Cells Is Mediated in Part from Secretion of the Antimicrobial Peptide LL‐37 , 2010, Stem cells.

[23]  Geert Carmeliet,et al.  Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. , 2010, Developmental cell.

[24]  F. Guilak,et al.  Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix. , 2010, Tissue engineering. Part A.

[25]  D. Covas,et al.  Mechanisms involved in the therapeutic properties of mesenchymal stem cells. , 2009, Cytokine & growth factor reviews.

[26]  V. Murugan Embryonic Stem Cell Research: A Decade of Debate from Bush to Obama , 2009, The Yale journal of biology and medicine.

[27]  B. Russell,et al.  Stem Cell Therapy for Cardiac Repair , 2009, The Journal of cardiovascular nursing.

[28]  J. García-Verdugo,et al.  A specialized vascular niche for adult neural stem cells. , 2008, Cell stem cell.

[29]  S. Badylak,et al.  A perivascular origin for mesenchymal stem cells in multiple human organs. , 2008, Cell stem cell.

[30]  Arnold I Caplan,et al.  All MSCs are pericytes? , 2008, Cell stem cell.

[31]  A. Caplan,et al.  Mesenchymal stem cells as trophic mediators , 2006, Journal of cellular biochemistry.

[32]  P. Oettgen,et al.  Is stem cell therapy ready for patients? Stem Cell Therapy for Cardiac Repair. Ready for the Next Step . , 2006, Circulation.

[33]  J. Huard,et al.  Long-term self-renewal of postnatal muscle-derived stem cells. , 2005, Molecular biology of the cell.

[34]  A. Caplan,et al.  Advances in mesenchymal stem cell biology , 2004 .

[35]  G. Vogel,et al.  Renovating the Heart , 2004, Science.

[36]  A. Lindahl,et al.  Phenotypic Plasticity of Human Articular Chondrocytes , 2003, The Journal of bone and joint surgery. American volume.

[37]  G. Sukhikh,et al.  Mesenchymal Stem Cells , 2002, Bulletin of Experimental Biology and Medicine.

[38]  A. Caplan,et al.  The STRO-1+ Marrow Cell Population Is Multipotential , 2001, Cells Tissues Organs.

[39]  P. Hernigou Autologous bone marrow grafting of avascular osteonecrosis before collapse , 2001, Arthritis Research.

[40]  P. Bianco,et al.  Marrow stromal stem cells. , 2000, The Journal of clinical investigation.

[41]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[42]  V. Goldberg,et al.  The Chondrogenic Potential of Human Bone-Marrow-Derived Mesenchymal Progenitor Cells* , 1998, The Journal of bone and joint surgery. American volume.

[43]  A. Reddi,et al.  Role of morphogenetic proteins in skeletal tissue engineering and regeneration , 1998, Nature Biotechnology.

[44]  M. Grompe,et al.  Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes. , 1997, The American journal of pathology.

[45]  Scott P. Bruder,et al.  Human and animal mesenchymal progenitor cells from bone marrow: Identification of serum for optimal selection and proliferation , 1996, In Vitro Cellular & Developmental Biology - Animal.

[46]  A. Reddi Bone and cartilage differentiation. , 1994, Current opinion in genetics & development.

[47]  A I Caplan,et al.  The mesengenic process. , 1994, Clinics in plastic surgery.

[48]  D. Connolly Kids' concept of cigarette code. , 1991, Journal of the American Medical Association (JAMA).

[49]  J F Connolly,et al.  Autologous marrow injection as a substitute for operative grafting of tibial nonunions. , 1991, Clinical orthopaedics and related research.

[50]  A. Caplan Cartilage begets bone versus endochondral myelopoiesis. , 1990, Clinical orthopaedics and related research.

[51]  V. Rosen,et al.  Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[52]  V. Goldberg,et al.  In vivo osteochondrogenic potential of cultured cells derived from the periosteum. , 1990, Clinical orthopaedics and related research.

[53]  A. Caplan Stem cell delivery vehicle. , 1990, Biomaterials.

[54]  J. Connolly,et al.  Development of an osteogenic bone-marrow preparation. , 1989, The Journal of bone and joint surgery. American volume.

[55]  V. Rosen,et al.  Novel regulators of bone formation: molecular clones and activities. , 1988, Science.

[56]  A. Caplan Bone development and repair , 1987, BioEssays : news and reviews in molecular, cellular and developmental biology.

[57]  R. Reiter,et al.  Environmental regulation of type X collagen production by cultures of limb mesenchyme, mesectoderm, and sternal chondrocytes. , 1986, Developmental biology.

[58]  A. Caplan,et al.  The in vitro chondrogenic response of limb-bud mesenchyme to a water-soluble fraction prepared from demineralized bone matrix. , 1985, Differentiation; research in biological diversity.

[59]  T. Schmid,et al.  Immunohistochemical localization of short chain cartilage collagen (type X) in avian tissues , 1985, The Journal of cell biology.

[60]  A. Caplan,et al.  A fraction from extracts of demineralized adult bone stimulates the conversion of mesenchymal cells into chondrocytes. , 1984, Developmental biology.

[61]  A. Caplan,et al.  The development of embryonic bone and cartilage in tissue culture. , 1983, Clinical orthopaedics and related research.

[62]  A. Caplan,et al.  Isolation and preliminary characterization of proteoglycans synthesized by skeletal muscle. , 1982, The Journal of biological chemistry.

[63]  A. Caplan,et al.  Characterization of a bone-specific alkaline phosphatase in chick limb mesenchymal cell cultures. , 1981, Developmental biology.

[64]  A. Caplan,et al.  First bone formation in the developing chick limb. , 1981, Developmental biology.

[65]  M. Urist,et al.  Solubilized and insolubilized bone morphogenetic protein. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[66]  M. Kay,et al.  Lexemic change and semantic shift in disease names , 1979, Culture, medicine and psychiatry.

[67]  V. Hascall,et al.  Biosynthesis of proteoglycans by chick limb bud chondrocytes. , 1978, The Journal of biological chemistry.

[68]  A. Caplan,et al.  The possible differentiation of osteogenic elements in vitro from chick limb mesodermal cells. I. Morphological evidence. , 1976, Developmental biology.

[69]  T. Oegema,et al.  Isolation and characterization of proteoglycans from chick limb bud chondrocytes grown in vitro. , 1976, The Journal of biological chemistry.

[70]  A. Caplan,et al.  Interrelationship between poly (ADP-Rib) synthesis, intracellular NAD levels, and muscle or cartilage differentiation from mesodermal cells of embryonic chick limb. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[71]  A. Caplan,et al.  Nicotinamide adenine dinucleotide levels in cells of developing chick limbs: possible control of muscle and cartilage development. , 1974, Developmental biology.

[72]  A. Caplan,et al.  Control of chondrogenic expression in mesodermal cells of embryonic chick limb. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[73]  A. Caplan,et al.  The control of muscle and cartilage development in the chick limb: the role of differential vascularization. , 1973, Journal of embryology and experimental morphology.

[74]  A. Reddi,et al.  Biochemical sequences in the transformation of normal fibroblasts in adolescent rats. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[75]  M. Urist,et al.  Inductive substrates for bone formation. , 1968, Clinical orthopaedics and related research.

[76]  N. Kaplan,et al.  3-Acetylpyridine: Effects in vitro Related to Teratogenic Activity in Chicken Embryos , 1968, Science.

[77]  A. Friedenstein,et al.  Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. , 1968, Transplantation.

[78]  M. Urist,et al.  Bone: Formation by Autoinduction , 1965, Science.

[79]  H. B. Fell The histogenesis of cartilage and bone in the long bones of the embryonic fowl , 1925 .

[80]  A. Caplan,et al.  Serial transplantation and long-term engraftment of intra-arterially delivered clonally derived mesenchymal stem cells to injured bone marrow. , 2014, Molecular Therapy.

[81]  F. Marini,et al.  Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. , 2005, Cytotherapy.

[82]  A I Caplan,et al.  Characterization of cells with osteogenic potential from human marrow. , 1992, Bone.

[83]  A. Caplan Cell delivery and tissue regeneration , 1990 .

[84]  R. Shprintzen,et al.  What's in a name? , 1990, The Cleft palate journal.

[85]  A. Friedenstein,et al.  Stromal stem cells: marrow-derived osteogenic precursors. , 1988, Ciba Foundation symposium.

[86]  A. Caplan,et al.  Proteoglycans produced by skeletal muscle in vitro and in vivo. , 1982, Progress in clinical and biological research.

[87]  N. Kulagina,et al.  Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. , 1974, Experimental hematology.