Abstract
Mesenchymal stem cells (MSCs) are somatic stem cells endowed with extraordinary regenerative and immunomodulatory properties that have been used in over 100 clinical trials worldwide to date. Their accessibility from autologous sources and safety when used in allogeneic transplantation make them ideal candidates from a wide variety of cell therapies. On the other hand, our limited understanding of their ontogeny, physiological role, and in vivo behavior currently limits the efficacy of MSC-based therapies. More specifically, MSC-like cells can be procured from many organs and tissues, but it is still unclear how these relate to the traditional marrow-derived MSCs in terms of developmental origin, behavior, and therapeutic efficacy. Furthermore, there is still some uncertainty about the mechanisms by which MSCs home to sites of injury and participate in tissue repair. This chapter will review our current understanding about these various issues, including the characterization and ontogeny of marrow-derived MSCs, alternative MSC sources, trafficking and homing of MSCs, and mechanisms of tissue repair.
Keywords
- Mesenchymal Stem Cell
- Human MSCs
- Bone Marrow MSCs
- Lateral Plate Mesoderm
- Total Peripheral Blood Mononuclear Cell
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Alm JJ, Koivu HM, Heino TJ, Hentunen TA, Laitinen S, Aro HT (2010) Circulating plastic adherent mesenchymal stem cells in aged hip fracture patients. J Orthop Res 28:1634–1642
Arai F, Ohneda O, Miyamoto T, Zhang XQ, Suda T (2002) Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation. J Exp Med 195:1549–1563
Barbash IM, Chouraqui P, Baron J et al (2003) Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 108:863–868
Becker AJ, McCulloch CA, Till JE (1963) Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:452–454
Bianco P, Robey PG, Saggio I, Riminucci M (2010) “Mesenchymal” stem cells in human bone marrow (skeletal stem cells): a critical discussion of their nature, identity, and significance in incurable skeletal disease. Hum Gene Ther 21:1057–1066
Bieback K, Kern S, Kluter H, Eichler H (2004) Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 22:625–634
Bonyadi M, Waldman SD, Liu D, Aubin JE, Grynpas MD, Stanford WL (2003) Mesenchymal progenitor self-renewal deficiency leads to age-dependent osteoporosis in Sca-1/Ly-6A null mice. Proc Natl Acad Sci USA 100:5840–5845
Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9:641–650
Carreras A, Almendros I, Acerbi I, Montserrat JM, Navajas D, Farré R (2009) Obstructive apneas induce early release of mesenchymal stem cells into circulating blood. Sleep 32:117–119
Chamberlain G, Wright K, Rot A, Ashton B, Middleton J (2008) Murine mesenchymal stem cells exhibit a restricted repertoire of functional chemokine receptors: comparison with human. PLoS One 3:e2934
Chen K, Wang D, Du WT et al (2010) Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism. Clin Immunol 135:448–458
Cohnheim J (1867) Ueber entzündung und eiterung. Path Anat Physiol Klin Med 40:1–79
Colnot C (2009) Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration. J Bone Miner Res 24:274–282
Colnot C, Lu C, Hu D, Helms JA (2004) Distinguishing the contributions of the perichondrium, cartilage, and vascular endothelium to skeletal development. Dev Biol 269:55–69
Colter DC, Sekiya I, Prockop DJ (2001) Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proc Natl Acad Sci USA 98:7841–7845
Coutu DL, Yousefi AM, Galipeau J (2009) Three-dimensional porous scaffolds at the crossroads of tissue engineering and cell-based gene therapy. J Cell Biochem 108:537–546
Crisan M, Yap S, Casteilla L et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–313
Cutler AJ, Limbani V, Girdlestone J, Navarrete CV (2010) Umbilical cord-derived mesenchymal stromal cells modulate monocyte function to suppress T cell proliferation. J Immunol 185:6617–6623
da Silva ML, Caplan AI, Nardi NB (2008) In search of the in vivo identity of mesenchymal stem cells. Stem Cells 26:2287–2299
Dalle CL, Valenti MT, Zanatta M, Donatelli L, Lo CV (2009) Circulating mesenchymal stem cells with abnormal osteogenic differentiation in patients with osteoporosis. Arthritis Rheum 60:3356–3365
De Becker A, Van Hummelen P, Bakkus M et al (2007) Migration of culture-expanded human mesenchymal stem cells through bone marrow endothelium is regulated by matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3. Haematologica 92:440–449
Deak E, Seifried E, Henschler R (2010) Homing pathways of mesenchymal stromal cells (MSCs) and their role in clinical applications. Int Rev Immunol 29:514–529
Devine SM, Cobbs C, Jennings M, Bartholomew A, Hoffman R (2003) Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood 101:2999–3001
Diaz-Flores,L., Gutierrez,R., Lopez-Alonso,A., Gonzalez R, Varela H. (1992). Pericytes as a supplementary source of osteoblasts in periosteal osteogenesis. Clin. Orthop. Relat Res. 280–286.
Eghbali-Fatourechi GZ, Lamsam J, Fraser D, Nagel D, Riggs BL, Khosla S (2005) Circulating osteoblast-lineage cells in humans. N Engl J Med 352:1959–1966
Fischer-Valuck BW, Barrilleaux BL, Phinney DG, Russell KC, Prockop DJ, O’Connor KC (2010) Migratory response of mesenchymal stem cells to macrophage migration inhibitory factor and its antagonist as a function of colony-forming efficiency. Biotechnol Lett 32:19–27
Flynn A, Barry F, O’Brien T (2007) UC blood-derived mesenchymal stromal cells: an overview. Cytotherapy 9:717–726
Fox JM, Chamberlain G, Ashton BA, Middleton J (2007) Recent advances into the understanding of mesenchymal stem cell trafficking. Br J Haematol 137:491–502
Francese R, Fiorina P (2010) Immunological and regenerative properties of cord blood stem cells. Clin Immunol 136:309–322
Francois S, Bensidhoum M, Mouiseddine M et al (2006) Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs: a study of their quantitative distribution after irradiation damage. Stem Cells 24:1020–1029
Friedenstein A (1989) Stromal-hematopoietic interrelationships: Maximov’s ideas and modern models. Haematol Blood Transfus 32:159–167
Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV (1974) Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 17:331–340
Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6:230–247
Gao J, Dennis JE, Muzic RF, Lundberg M, Caplan AI (2001) The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs 169:12–20
Gimble J, Guilak F (2003) Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy 5:362–369
Girdlestone J, Limbani VA, Cutler AJ, Navarrete CV (2009) Efficient expansion of mesenchymal stromal cells from umbilical cord under low serum conditions. Cytotherapy 11(6):738–748
Goujon E (1869) Recherches expérimentales sur les propriétés physiologiques de la moelle des os. Journal de l’anatomie et de la physiologie normales et pathologiques de l’homme et des animaux 6:399–412
Haeckel E (1868) Natürliche Schöpfungsgeschichte, G. Reimer, ed. Berlin
Hattori H, Sato M, Masuoka K et al (2004) Osteogenic potential of human adipose tissue-derived stromal cells as an alternative stem cell source. Cells Tissues Organs 178:2–12
Hayashi O, Katsube Y, Hirose M, Ohgushi H, Ito H (2008) Comparison of osteogenic ability of rat mesenchymal stem cells from bone marrow, periosteum, and adipose tissue. Calcif Tissue Int 82:238–247
He Q, Wan C, Li G (2007) Concise review: multipotent mesenchymal stromal cells in blood. Stem Cells 25:69–77
Honczarenko M, Le Y, Swierkowski M, Ghiran I, Glodek AM, Silberstein LE (2006) Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells 24:1030–1041
Horwitz EM, Le Blanc K, Dominici M et al (2005) Clarification of the nomenclature for MSC: the international society for cellular therapy position statement. Cytotherapy 7:393–395
Horwitz EM, Prockop DJ, Fitzpatrick LA et al (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5:309–313
Im GI, Shin YW, Lee KB (2005) Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthritis Cartilage 13:845–853
Izadpanah R, Trygg C, Patel B et al (2006) Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem 99:1285–1297
Karp JM, Leng Teo GS (2009) Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell 4:206–216
Karsenty G, Kronenberg HM, Settembre C (2009) Genetic control of bone formation. Annu Rev Cell Dev Biol 25:629–648
Kogler G, Sensken S, Airey JA et al (2004) A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 200:123–135
Kronenberg HM (2003) Developmental regulation of the growth plate. Nature 423:332–336
Kronenberg HM (2007) The role of the perichondrium in fetal bone development. Ann N Y Acad Sci 1116:59–64
Kuznetsov SA, Mankani MH, Gronthos S, Satomura K, Bianco P, Robey PG (2001) Circulating skeletal stem cells. J Cell Biol 153:1133–1140
Laflamme MA, Murry CE (2005) Regenerating the heart. Nat Biotechnol 23:845–856
Laitinen A, Laine J (2007) Isolation of mesenchymal stem cells from human cord blood. Curr Protoc Stem Cell Biol, Chapter 2, Unit
Lee RH, Seo MJ, Pulin AA, Gregory CA, Ylostalo J, Prockop DJ (2009) The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice. Blood 113:816–826
Liechty KW, MacKenzie TC, Shaaban AF et al (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6:1282–1286
Lu X, Alshemali S, de Wynter EA, Dickinson AM (2010) Mesenchymal stem cells from CD34(−) human umbilical cord blood. Transfus Med 20:178–184
Maes C, Kobayashi T, Kronenberg HM (2007) A novel transgenic mouse model to study the osteoblast lineage in vivo. Ann N Y Acad Sci 1116:149–164
Maes C, Kobayashi T, Selig MK et al (2010) Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell 19:329–344
Mansilla E, Marin GH, Drago H et al (2006) Bloodstream cells phenotypically identical to human mesenchymal bone marrow stem cells circulate in large amounts under the influence of acute large skin damage: new evidence for their use in regenerative medicine. Transplant Proc 38:967–969
Mariani FV, Martin GR (2003) Deciphering skeletal patterning: clues from the limb. Nature 423:319–325
Maximov A (1909) Der Lymphozyt als gemeinsame Stammzelle der verschiedenen Blutelemente in der embryonalen Entwicklung und im postfetalen Leben der Säugetiere. Folia Haematol 8:125–134
Mendez-Ferrer S, Michurina TV, Ferraro F et al (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466:829–834
Montesinos JJ, Flores-Figueroa E, Castillo-Medina S et al (2009) Human mesenchymal stromal cells from adult and neonatal sources: comparative analysis of their morphology, immunophenotype, differentiation patterns and neural protein expression. Cytotherapy 11:163–176
Morikawa S, Mabuchi Y, Kubota Y et al (2009) Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med 206:2483–2496
Mouiseddine M, Francois S, Semont A et al (2007) Human mesenchymal stem cells home specifically to radiation-injured tissues in a non-obese diabetes/severe combined immunodeficiency mouse model. Br J Radiol 80(Spec. No. 1):S49–S55
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. Eur Cell Mater 19:127–135
Nagasawa T (2006) Microenvironmental niches in the bone marrow required for B-cell development. Nat Rev Immunol 6:107–116
Nagaya N, Fujii T, Iwase T et al (2004) Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol 287:H2670–H2676
Ohgushi H, Caplan AI (1999) Stem cell technology and bioceramics: from cell to gene engineering. J Biomed Mater Res 48:913–927
Ortiz LA, DuTreil M, Fattman C et al (2007) Interleukin 1 receptor antagonist mediates the anti-inflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci USA 104:11002–11007
Ortiz LA, Gambelli F, McBride C et al (2003) Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci USA 100:8407–8411
Otsuru S, Tamai K, Yamazaki T, Yoshikawa H, Kaneda Y (2008) Circulating bone marrow-derived osteoblast progenitor cells are recruited to the bone-forming site by the CXCR4/stromal cell-derived factor-1 pathway. Stem Cells 26:223–234
Pappa KI, Anagnou NP (2009) Novel sources of fetal stem cells: where do they fit on the developmental continuum? Regen Med 4:423–433
Pappenheim A (1896) Ueber Entwickelung und Ausbildung der Erythroblasten. Virchows Arch 145:586–643
Phinney DG, Prockop DJ (2007) Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair–current views. Stem Cells 25:2896–2902
Pitchford SC, Furze RC, Jones CP, Wengner AM, Rankin SM (2009) Differential mobilization of subsets of progenitor cells from the bone marrow. Cell Stem Cell 4:62–72
Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147
Pittenger MF, Martin BJ (2004) Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 95:9–20
Ponte AL, Marais E, Gallay N et al (2007) The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells 25:1737–1745
Price MJ, Chou CC, Frantzen M et al (2006) Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. Int J Cardiol 111:231–239
Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74
Prockop DJ (2007) “Stemness” does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs). Clin Pharmacol Ther 82:241–243
Prockop DJ (2009) Repair of tissues by adult stem/progenitor cells (MSCs): controversies, myths, and changing paradigms. Mol Ther 17:939–946
Prockop DJ, Gregory CA, Spees JL (2003) One strategy for cell and gene therapy: harnessing the power of adult stem cells to repair tissues. Proc Natl Acad Sci USA 100(Suppl 1):11917–11923
Prockop DJ, Kota DJ, Bazhanov N, Reger RL (2010) Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs). J. Cell Mol, Med
Prockop DJ, Olson SD (2007) Clinical trials with adult stem/progenitor cells for tissue repair: let’s not overlook some essential precautions. Blood 109:3147–3151
Psaltis PJ, Zannettino AC, Worthley SG, Gronthos S (2008) Concise review: mesenchymal stromal cells: potential for cardiovascular repair. Stem Cells 26:2201–2210
Ramalho-Santos M, Willenbring H (2007) On the origin of the term “stem cell”. Cell Stem Cell 1:35–38
Rebelatto CK, Aguiar AM, Moretao MP et al (2008) Dissimilar differentiation of mesenchymal stem cells from bone marrow, umbilical cord blood, and adipose tissue. Exp Biol Med (Maywood) 233:901–913
Ries C, Egea V, Karow M, Kolb H, Jochum M, Neth P (2007) MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood 109:4055–4063
Riordan NH, Ichim TE, Min WP et al (2009) Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis. J Transl Med 7:29
Rochefort GY, Delorme B, Lopez A et al (2006) Multipotential mesenchymal stem cells are mobilized into peripheral blood by hypoxia. Stem Cells 24:2202–2208
Ruster B, Gottig S, Ludwig RJ et al (2006) Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells. Blood 108:3938–3944
Sacchetti B, Funari A, Michienzi S et al (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324–336
Sackstein R, Merzaban JS, Cain DW et al (2008) Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nat Med 14:181–187
Sakaguchi Y, Sekiya I, Yagishita K, Muneta T (2005) Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum 52:2521–2529
Schaffler A, Buchler C (2007) Concise review: adipose tissue-derived stromal cells–basic and clinical implications for novel cell-based therapies. Stem Cells 25:818–827
Scherberich A, Galli R, Jaquiery C, Farhadi J, Martin I (2007) Three-dimensional perfusion culture of human adipose tissue-derived endothelial and osteoblastic progenitors generates osteogenic constructs with intrinsic vascularization capacity. Stem Cells 25:1823–1829
Schipani E, Kronenberg HM (2009) Adult mesenchymal stem cells. In StemBook. The Stem Cell Research Community, http://www.stembook.org/
Segers VF, Lee RT (2008) Stem-cell therapy for cardiac disease. Nature 451:937–942
Simmons PJ, Torok-Storb B (1991) Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood 78:55–62
Srouji S, Kizhner T, Livne E (2006) 3D scaffolds for bone marrow stem cell support in bone repair. Regen Med 1:519–528
Sun L, Wang D, Liang J et al (2010) Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum 62:2467–2475
Tang YL, Zhu W, Cheng M et al (2009) Hypoxic preconditioning enhances the benefit of cardiac progenitor cell therapy for treatment of myocardial infarction by inducing CXCR4 expression. Circ Res 104:1209–1216
Tavassoli M, Crosby WH (1968) Transplantation of marrow to extramedullary sites. Science 161:54–56
Tokoyoda K, Egawa T, Sugiyama T et al (2004) Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity 20:707–718
Tuli R, Tuli S, Nandi S et al (2003) Characterization of multipotential mesenchymal progenitor cells derived from human trabecular bone. Stem Cells 21:681–693
Wagner W, Wein F, Seckinger A et al (2005) Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 33:1402–1416
Wang M, Yang Y, Yang D et al (2009) The immunomodulatory activity of human umbilical cord blood-derived mesenchymal stem cells in vitro. Immunology 126:220–232
Wang Y, Johnsen HE, Mortensen S et al (2006) Changes in circulating mesenchymal stem cells, stem cell homing factor, and vascular growth factors in patients with acute ST elevation myocardial infarction treated with primary percutaneous coronary intervention. Heart 92:768–774
Weiss DJ, Kolls JK, Ortiz LA, Panoskaltsis-Mortari A, Prockop DJ (2008) Stem cells and cell therapies in lung biology and lung diseases. Proc Am Thorac Soc 5:637–667
Wexler SA, Donaldson C, Denning-Kendall P, Rice C, Bradley B, Hows JM (2003) Adult bone marrow is a rich source of human mesenchymal ‘stem’ cells but umbilical cord and mobilized adult blood are not. Br J Haematol 121:368–374
Yoshimura H, Muneta T, Nimura A, Yokoyama A, Koga H, Sekiya I (2007) Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res 327:449–462
Yu J, Li M, Qu Z et al (2010) SDF-1/CXCR4-mediated migration of transplanted bone marrow stromal cells toward areas of heart myocardial infarction through activation of PI3K/Akt. J Cardiovasc Pharmacol 55:496–505
Zabouo G, Imbert AM, Jacquemier J et al (2009) CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines. Breast Cancer Res 11:R1
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Coutu, D.L., François, M., Galipeau, J. (2012). Mesenchymal Stem Cells and Tissue Repair. In: Allan, D., Strunk, D. (eds) Regenerative Therapy Using Blood-Derived Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-61779-471-1_4
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