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2015 | 62 | 3 | 329-337
Article title

Adult stem cells: hopes and hypes of regenerative medicine

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EN
Abstracts
EN
Stem cells are self-renewing cells that can differentiate into specialized cell type(s). Pluripotent stem cells, i.e. embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) differentiate into cells of all three embryonic lineages. Multipotent stem cells, like hematopoietic stem cells (HSC), can develop into multiple specialized cells in a specific tissue. Unipotent cells differentiate only into one cell type, like e.g. satellite cells of skeletal muscle. There are many examples of successful clinical applications of stem cells. Over million patients worldwide have benefited from bone marrow transplantations performed for treatment of leukemias, anemias or immunodeficiencies. Skin stem cells are used to heal severe burns, while limbal stem cells can regenerate the damaged cornea. Pluripotent stem cells, especially the patient-specific iPSC, have a tremendous therapeutic potential, but their clinical application will require overcoming numerous drawbacks. Therefore, the use of adult stem cells, which are multipotent or unipotent, can be at present a more achievable strategy. Noteworthy, some studies ascribed particular adult stem cells as pluripotent. However, despite efforts, the postulated pluripotency of such events like "spore-like cells", "very small embryonic-like stem cells" or "multipotent adult progenitor cells" have not been confirmed in stringent independent studies. Also plasticity of the bone marrow-derived cells which were suggested to differentiate e.g. into cardiomyocytes, has not been positively verified, and their therapeutic effect, if observed, results rather from the paracrine activity. Here we discuss the examples of recent studies on adult stem cells in the light of current understanding of stem cell biology.
Year
Volume
62
Issue
3
Pages
329-337
Physical description
Dates
published
2015
received
2015-04-07
revised
2015-04-26
accepted
2015-05-02
(unknown)
2015-07-22
References
  • Abbott A (2013) Doubt cast over tiny stem cells. Nature 499: 390-390.
  • Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer K, Lois C, Morrison SJ, Alvarez-Buylla A (2003) Fusion of bone-marrow-derived cells with Purkinje neurons cardiomyocytes and hepatocytes. Nature 425: 968-973.
  • Alvarez-Gonzalez C, Duggleby R, Vagaska B, Querol S, Gomez SG, Ferretti P, Madrigal A (2013) Cord blood Lin(-)CD45(-) embryonic-like stem cells are a heterogeneous population that lack self-renewal capacity. PloS One 8: e67968.
  • Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275: 964-967.
  • Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85: 221-228.
  • Assmus B, Schächinger V, Teupe C, Britten M, Lehmann R, Döbert N, Grünwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM (2002) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI) Circulation 106: 3009-3017.
  • Baker M (2007) Flawed data in multipotent cell study. Nat Rep Stem Cells
  • Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428: 668-673.
  • Bianco P (2014) 'Mesenchymal' stem cells. Annu Rev Cell Dev Biol 30: 677-704.
  • Bianco P, Barker R, Brüstle O, Cattaneo E, Clevers H, Daley GQ, De Luca M, Goldstein L, Lindvall O, Mummery C, Robey PG, Sattler de Sousa E Brito C, Smith A (2013) Regulation of stem cell therapies under attack in Europe: for whom the bell tolls. EMBO J 32: 1489-1495.
  • Bryder D, Rossi DJ, Weissman IL (2006) Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol 169: 338-346.
  • Bussolati B, Ahmed A, Pemberton H, Landis RC, Carlo FD, Haskard DO, Mason JC (2004) Bifunctional role for VEGF-induced heme oxygenase-1 in vivo: induction of angiogenesis and inhibition of leukocytic infiltration. Blood 103: 761-766.
  • Check E (2007) Stem cells: the hard copy. Nature 446: 485-486.
  • Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Chopp M (2001) Therapeutic Benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32: 1005-1011.
  • Choudry FA, Mathur A (2011) Stem cell therapy in cardiology. Regen Med 6: 17-23.
  • Couzin-Frankel J (2014) The elusive heart fix. Science 345: 252-257.
  • Cyranoski D (2014a) Stem-cell scientist found guilty of misconduct. Nature
  • Cyranoski D (2014b) Papers on 'stress-induced' stem cells are retracted. Nature
  • Cyranoski D (2014c) Stem-cell pioneer blamed media 'bashing' in suicide note. Nature
  • Cyranoski D (2014d) Still no stem cells via easy 'STAP' path. Nature
  • Dahl JA, Duggal S, Coulston N, Millar D, Melki J, Shahdadfar A, Brinchmann JE, Collas P (2008) Genetic and epigenetic instability of human bone marrow mesenchymal stem cells expanded in autologous serum or fetal bovine serum. Int J Dev Biol 52: 1033-1042.
  • Danova-Alt R, Heider A, Egger D, Cross M, Alt R (2012) Very small embryonic-like stem cells purified from umbilical cord blood lack stem cell characteristics. PloS One 7: e34899.
  • Dawn B, Tiwari S, Kucia MJ, Zuba-Surma EK, Guo Y, Sanganalmath SK, Abdel-Latif A, Hunt G, Vincent RJ, Taher H, Reed NJ, Ratajczak MZ, Bolli R (2008) Transplantation of bone marrow-derived very small embryonic-like stem cells attenuates left ventricular dysfunction and remodeling after myocardial infarction. Stem Cells Dayt Ohio 26: 1646-1655.
  • Deramaudt BM, Braunstein S, Remy P, Abraham NG (1998) Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis J Cell Biochem 68: 121-127.
  • Dulak J, Józkowicz A, Foresti R, Kasza A, Frick M, Huk I, Green CJ, Pachinger O, Weidinger F, Motterlini R (2002) Heme oxygenase activity modulates vascular endothelial growth factor synthesis in vascular smooth muscle cells. Antioxid Redox Signal 4: 229-240.
  • Dulak J, Deshane J, Jozkowicz A, Agarwal A (2008) Heme oxygenase-1 and carbon monoxide in vascular pathobiology focus on angiogenesis. Circulation 117: 231-241.
  • Ferrari G, Cusella G, Angelis D, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, Mavilio F (1998) Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279: 1528-1530.
  • Grens K (2015) Hearts on trial. The Scientist 29: 47-52.
  • Grochot-Przeczek A, Kotlinowski J, Kozakowska M, Starowicz K, Jagodzinska J, Stachurska A, Volger OL, Bukowska-Strakova K, Florczyk U, Tertil M, Jazwa A, Szade K, Stepniewski J, Loboda A, Horrevoets AJ, Dulak J, Jozkowicz A (2014) Heme oxygenase-1 is required for angiogenic function of bone marrow-derived progenitor cells: role in therapeutic revascularization. Antioxid Redox Signal 20: 1677-1692.
  • Hess D, Li L, Martin M, Sakano S, Hill D, Strutt B, Thyssen S, Gray DA, Bhatia M (2003) Bone marrow-derived stem cells initiate pancreatic regeneration. Nat Biotechnol 21: 763-770.
  • Huang Y, Kucia M, Hussain LR, Wen Y, Xu H, Yan J, Ratajczak MZ, Ildstad ST (2010) Bone marrow transplantation temporarily improves pancreatic function in streptozotocin-induced diabetes: potential involvement of very small embryonic-like cells. Transplantation 89: 677-685.
  • Jaenisch R, Young R (2008) Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132: 567-582.
  • Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418: 41-49.
  • de Jong R, Houtgraaf JH, Samiei S, Boersma E, Duckers HJ (2014) Intracoronary stem cell infusion after acute myocardial infarction a meta-analysis and update on clinical trials. Circ Cardiovasc Interv 7: 156-167.
  • Józkowicz A, Huk I, Nigisch A, Weigel G, Dietrich W, Motterlini R, Dulak J (2003) Heme oxygenase and angiogenic activity of endothelial cells: stimulation by carbon monoxide and inhibition by tin protoporphyrin-IX. Antioxid Redox Signal 5: 155-162.
  • Kale S, Karihaloo A, Clark PR, Kashgarian M, Krause DS, Cantley LG (2003) Bone marrow stem cells contribute to repair of the ischemically injured renal tubule. J Clin Invest 112: 42-49.
  • Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M, Li T, Isner JM, Asahara T (2000) Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A 97: 3422-3427.
  • Kaltz N, Funari A, Hippauf S, Delorme B, Noël D, Riminucci M, Jacobs VR, Häupl T, Jorgensen C, Charbord P, Peschel C, Bianco P, Oostendorp RA (2008) In vivo osteoprogenitor potency of human stromal cells from different tissues does not correlate with expression of POU5F1 or its pseudogenes. Stem Cells Dayt Ohio 26: 2419-2424.
  • Kamihata H, Matsubara H, Nishiue T, Fujiyama S, Tsutsumi Y, Ozono R, Masaki H, Mori Y, Iba O, Tateishi E, Kosaki A, Shintani S, Murohara T, Imaizumi T, Iwasaka T (2001) Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts angiogenic ligands and cytokines. Circulation 104: 1046-1052.
  • Kataoka K, Medina RJ, Kageyama T, Miyazaki M, Yoshino T, Makino T, Huh N (2003) Participation of adult mouse bone marrow cells in reconstitution of skin. Am J Pathol 163: 1227-1231.
  • Knoepfler (2014) Interview with Charles Vacanti on STAP Cells: Link to Spore Stem Cells & More.
  • Kucia M, Reca R, Campbell FR, Zuba-Surma E, Majka M, Ratajczak J, Ratajczak MZ (2006) A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4+stem cells identified in adult bone marrow. Leukemia 20: 857-869.
  • Lakkisto P, Siren JM, Kytö V, Forsten H, Laine M, Pulkki K, Tikkanen I (2011) Heme oxygenase-1 induction protects the heart and modulates cellular and extracellular remodelling after myocardial infarction in rats. Exp Biol Med 236: 1437-1448.
  • Li H, Fan X, Kovi RC, Jo Y, Moquin B, Konz R, Stoicov C, Kurt-Jones E, Grossman SR, Lyle S, Rogers AB, Montrose M, Houghton J (2007) Spontaneous expression of embryonic factors and p53 point mutations in aged mesenchymal stem cells: a model of age-related tumorigenesis in mice. Cancer Res 67: 10889-10898.
  • Liedtke S, Enczmann J, Waclawczyk S, Wernet P, Kögler G (2007) Oct4 and its pseudogenes confuse stem cell research. Cell Stem Cell 1: 364-366.
  • Liedtke S, Stephan M, Kögler G (2008) Oct4 expression revisited: potential pitfalls for data misinterpretation in stem cell research. Biol Chem 389: 845-850.
  • Mezey É, Chandross KJ, Harta G, Maki RA, McKercher SR (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290: 1779-1782.
  • Miyanishi M, Mori Y, Seita J, Chen JY, Karten S, Chan CK, Nakauchi H, Weissman IL (2013) Do pluripotent stem cells exist in adult mice as very small embryonic stem cells? Stem Cell Reports 1: 198-208.
  • Müller FJ, Goldmann J, Löser P, Loring JF (2010) A call to standardize teratoma assays used to define human pluripotent cell lines. Cell Stem Cell 6: 412-414.
  • Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Pasumarthi KB, Virag JI, Bartelmez SH, Poppa V, Bradford G, Dowell JD, Williams DA, Field LJ (2004) Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428: 664-668.
  • Normile D, Vogel G (2014) Stem cells. Irreproducibility dogs new reprogramming method. Science 343: 1299-1300.
  • Nowbar AN, Mielewczik M, Karavassilis M, Dehbi HM, Shun-Shin MJ, Jones S, Howard JP, Cole GD, Francis DP (2014) Discrepancies in autologous bone marrow stem cell trials and enhancement of ejection fraction (DAMASCENE): weighted regression and meta-analysis. BMJ 348: g2688.
  • Nygren JM, Jovinge S, Breitbach M, Säwén P, Röll W, Hescheler J, Taneera J, Fleischmann BK, Jacobsen SE (2004) Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion but not transdifferentiation. Nat Med 10: 494-501.
  • Obokata H, Wakayama T, Sasai Y, Kojima K, Vacanti MP, Niwa H, Yamato M, Vacanti CA (2014a) Retraction: Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature 511: 112-112.
  • Obokata H, Sasai Y, Niwa H, Kadota M, Andrabi M, Takata N, Tokoro M, Terashita Y, Yonemura S, Vacanti CA, Wakayama T (2014b) Retraction: Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. Nature 511: 112-112.
  • Obokata H, Wakayama T, Sasai Y, Kojima K, Vacanti MP, Niwa H, Yamato M, Vacanti CA (2014c) Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature 505: 641-647.
  • Obokata H, Sasai Y, Niwa H, Kadota M, Andrabi M, Takata N, Tokoro M, Terashita Y, Yonemura S, Vacanti CA, Wakayama T (2014d) Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. Nature 505: 676-680.
  • Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410: 701-705.
  • Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Mesquita CT, Rossi MI, Carvalho AC, Dutra HS, Dohmann HJ, Silva GV, Belem L, Vivacqua R, Rangel FO, Esporcatte R, Geng YJ, Vaughn WK, Assad JA, Mesquita ET, Willerson JT (2003) Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 107: 2294-2302.
  • Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP (1999) Bone marrow as a potential source of hepatic oval cells. Science 284: 1168-1170.
  • 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.
  • Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G (2010) Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med 363: 147-155.
  • Ratajczak J, Zuba-Surma E, Paczkowska E, Kucia M, Nowacki P, Ratajczak MZ (2011a) Stem cells for neural regeneration - a potential application of very small embryonic-like stem cells. J Physiol Pharmacol 62: 3-12.
  • Ratajczak J, Wysoczynski M, Zuba-Surma E, Wan W, Kucia M, Yoder MC, Ratajczak MZ (2011b) Adult murine bone marrow-derived very small embryonic-like stem cells differentiate into the hematopoietic lineage after coculture over OP9 stromal cells. Exp Hematol 39: 225-237.
  • Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, Lanza R (2012) Embryonic stem cell trials for macular degeneration: a preliminary report. The Lancet 379: 713-720.
  • Spade PV Panaccio C (2011) William of Ockham. The Stanford Encyclopedia of Philosophy (Fall 2011 Edition) Zalta EN ed. Stanford Stanford University URL
  • Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, Schümichen C, Nienaber CA, Freund M, Steinhoff G (2003) Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361: 45-46.
  • Strauer BE, Brehm M, Zeus T, Köstering M, Hernandez A, Sorg RV, Kögler G, Wernet P (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106: 1913-1918.
  • Szade K, Zuba-Surma E, Rutkowsk AJ, Jozkowicz A, Dulak J (2011) CD45-CD14 +CD34 + murine bone marrow low-adherent mesenchymal primitive cells preserve multilineage differentiation potential in long-term in vitro culture. Mol Cells 31: 497-507.
  • Szade K, Bukowska-Strakova K, Nowak WN, Szade A, Kachamakova-Trojanowska N, Zukowska M, Jozkowicz A, Dulak J (2013) Murine bone marrow Lin-Sca-1+CD45- very small embryonic-like (VSEL) cells are heterogeneous population lacking Oct-4A expression. PloS One 8: e63329.
  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663-676.
  • Tang YL, Tang Y, Zhang YC, Qian K, Shen L, Phillips MI (2005) Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. J Am Coll Cardiol 46: 1339-1350.
  • Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, Meyer EM, Morel L, Petersen BE, Scott EW (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416: 542-545.
  • Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S, Xia L, Zhou N, Riddle M, Schroeder TM, Westendorf JJ, McIvor RS, Hogendoorn PC, Szuhai K, Oseth L, Hirsch B, Yant SR, Kay MA, Peister A, Prockop DJ, Fibbe WE, Blazar BR (2007) Sarcoma derived from cultured mesenchymal stem cells. Stem Cells Dayt Ohio 25: 371-379.
  • Vacanti MP, Roy A, Cortiella J, Bonassar L, Vacanti CA (2001) Identification and initial characterization of spore-like cells in adult mammals. J Cell Biochem 80: 455-460.
  • Wagers AJ, Weissman IL (2004) Plasticity of adult stem cells. Cell 116: 639-648.
  • Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M (2003) Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422: 897-901.
  • Weissman IL (2000) Stem cells: units of development units of regeneration and units in evolution. Cell 100: 157-168.
  • Wojakowski W, Tendera M, Cybulski W, Zuba-Surma EK, Szade K, Florczyk U, Kozakowska M, Szymula A, Krzych L, Paslawska U, Paslawski R, Milewski K, Buszman PP, Nabialek E, Kuczmik W, Janiszewski A, Dziegiel P, Buszman PE, Jozkowicz A, Dulak J (2012) Effects of intracoronary delivery of allogenic bone marrow-derived stem cells expressing heme oxygenase-1 on myocardial reperfusion injury. Thromb Haemost 108: 464-475.
  • Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, Fichtner S, Korte T, Hornig B, Messinger D, Arseniev L, Hertenstein B, Ganser A, Drexler H (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364: 141-148.
  • Zuba-Surma EK, Kucia M, Ratajczak J, Ratajczak MZ (2009) 'Small Stem Cells' in adult tissues: very small embryonic-like stem cells (VSELs) stand up! Cytometry A 75: 4-13.
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