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Mesenchymale Stammzellen

Von der Biologie zum klinischen Einsatz

Mesenchymal stem cells

From biology to clinical application

  • Leitthema
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Monatsschrift Kinderheilkunde Aims and scope Submit manuscript

Zusammenfassung

Bindegewebsstammzellen oder mesenchymale Stammzellen besitzen ein breites Differenzierungspotenzial, unterstützen die Blutbildung und die körpereigene Geweberegeneration und supprimieren zahlreiche Komponenten des Immunsystems. Basierend auf diesen Eigenschaften werden sie derzeit in verschiedenen klinischen Einsatzfeldern auf ihre Wirksamkeit und Sicherheit hin untersucht. Im Bereich der pädiatrischen Hämatoonkologie wurden erste, viel versprechende klinische Daten beim Einsatz zur Behandlung der steroidrefraktären Spender-Gegen-Empfänger-Erkrankung nach allogener Stammzelltransplantation und zur Behandlung von Osteonekrosen nach antineoplastischer Therapie berichtet. Sofern sich mesenchymale Stammzellen in prospektiven klinischen Studien als wirksam bezüglich der Immunmodulation und der Unterstützung der endogenen Geweberegeneration zeigen, stehen diesem neuen Zelltherapeutikum vielfältige klinische Anwendungsbereiche z. B. bei Autoimmunerkrankungen in der Pädiatrie offen, die weit über die genannten hämatologisch-onkologischen Applikationen hinausreichen.

Abstract

Mesenchymal stem cells exhibit multilineage differentiation potential and support endogenous tissue repair and haematopoiesis. In addition, they have been shown to inhibit proliferation and effector functions of various immune cells. Based on these properties, mesenchymal stem cells are currently under intensive preclinical and clinical investigation in different therapeutic applications. First promising data in children have been reported from the use of mesenchymal stem cells in steroid-refractory acute graft-versus-host disease following allogeneic stem cell transplantation and in the treatment of avascular osteonecrosis after cancer chemotherapy. If mesenchymal stem cells prove to be clinically efficacious in prospective clinical trials with regard to immunosuppression and support of endogenous tissue repair, they will represent a promising novel treatment option for various fields of application, including (but not limited to) paediatric autoimmune diseases, thus reaching far beyond the reported clinical experience in haemato-oncology.

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Literatur

  1. Bartholomew A, Sturgeon C, Siatskas M et al (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30:42–48

    Article  PubMed  Google Scholar 

  2. Bonin M von, Stolzel F, Goedecke A et al (2009) Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant 43:245–251

    Article  CAS  Google Scholar 

  3. Burger B, Beier R, Zimmermann M et al (2005) Osteonecrosis: a treatment related toxicity in childhood acute lymphoblastic leukemia (ALL) – experiences from trial ALL-BFM 95. Pediatr Blood Cancer 44:220–225

    Article  PubMed  Google Scholar 

  4. Calvi LM, Adams GB, Weibrecht KW et al (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–846

    Article  PubMed  CAS  Google Scholar 

  5. Christopeit M, Schendel M, Foll J et al (2008) Marked improvement of severe progressive systemic sclerosis after transplantation of mesenchymal stem cells from an allogeneic haploidentical-related donor mediated by ligation of CD137L. Leukemia 22:1062–1064

    Article  PubMed  CAS  Google Scholar 

  6. Deng W, Han Q, Liao L et al (2005) Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice. DNA Cell Biol 24:458–463

    Article  PubMed  CAS  Google Scholar 

  7. Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317

    Article  PubMed  CAS  Google Scholar 

  8. Friedenstein AJ, Gorskaja JF, Kulagina NN (1976) Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 4:267–274

    PubMed  CAS  Google Scholar 

  9. Guillot PV, Abass O, Bassett JH et al (2008) Intrauterine transplantation of human fetal mesenchymal stem cells from first-trimester blood repairs bone and reduces fractures in osteogenesis imperfecta mice. Blood 111:1717–1725

    Article  PubMed  CAS  Google Scholar 

  10. Guo J, Lin GS, Bao CY et al (2007) Anti-inflammation role for mesenchymal stem cells transplantation in myocardial infarction. Inflammation 30:97–104

    Article  PubMed  CAS  Google Scholar 

  11. Hare JM, Traverse JH, Henry TD et al (2009) A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol 54:2277–2286

    Article  PubMed  CAS  Google Scholar 

  12. 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

    Article  PubMed  CAS  Google Scholar 

  13. Hofstetter CP, Schwarz EJ, Hess D et al (2002) Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci USA 99:2199–2204

    Article  PubMed  CAS  Google Scholar 

  14. 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

    Article  PubMed  CAS  Google Scholar 

  15. Kuci S, Kuci Z, Kreyenberg H (2010) CD271 antigen defines a subset of multipotent stromal cells with immunosuppressive and lymphohematopoietic engraftment-promoting properties. Haematologica in press

  16. Kunter U, Rong S, Djuric Z et al (2006) Transplanted mesenchymal stem cells accelerate glomerular healing in experimental glomerulonephritis. J Am Soc Nephrol 17:2202–2212

    Article  PubMed  CAS  Google Scholar 

  17. Le Blanc K, Frassoni F, Ball L et al (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371:1579–1586

    Article  CAS  Google Scholar 

  18. Lee RH, Seo MJ, Reger RL et al (2006) Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice. Proc Natl Acad Sci USA 103:17438–17443

    Article  PubMed  CAS  Google Scholar 

  19. Meisel R, Zibert A, Laryea M et al (2004) Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 103:4619–4621

    Article  PubMed  CAS  Google Scholar 

  20. Müller I, Kustermann-Kuhn B, Holzwarth C et al (2006) In vitro analysis of multipotent mesenchymal stromal cells as potential cellular therapeutics in neurometabolic diseases in pediatric patients. Exp Hematol 34:1413–1419

    Article  PubMed  CAS  Google Scholar 

  21. Müller I, Kordowich S, Holzwarth C et al (2008) Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation. Blood Cells Mol Dis 40:25–32

    Article  PubMed  Google Scholar 

  22. Müller I, Vaegler M, Holzwarth C et al (2008) Secretion of angiogenic proteins by human multipotent mesenchymal stromal cells and their clinical potential in the treatment of avascular osteonecrosis. Leukemia 22:2054–2061

    Article  PubMed  CAS  Google Scholar 

  23. Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110:3499–3506

    Article  PubMed  CAS  Google Scholar 

  24. 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

    Article  PubMed  Google Scholar 

  25. Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

  26. Tisato V, Naresh K, Girdlestone J et al (2007) Mesenchymal stem cells of cord blood origin are effective at preventing but not treating graft-versus-host disease. Leukemia 21:1992–1999

    Article  PubMed  CAS  Google Scholar 

  27. Zappia E, Casazza S, Pedemonte E et al (2005) Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood 106:1755–1761

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Klinik für Kinder-Onkologie, -Hämatologie und Klinische Immunologie, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Deutschland

    R. Meisel

  2. Klinik III: Hämatologie, Onkologie und Hämostaseologie, Zentrum für Kinder- und Jugendmedizin, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt am Main, Deutschland

    S. Kuci

  3. Abteilung für Allgemeine Pädiatrie, Hämatologie/Onkologie, Universitätsklinik für Kinder- und Jugendmedizin Tübingen, Tübingen, Deutschland

    I. Müller

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  3. I. Müller
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Correspondence to R. Meisel.

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Meisel, R., Kuci, S. & Müller, I. Mesenchymale Stammzellen. Monatsschr Kinderheilkd 158, 240–245 (2010). https://doi.org/10.1007/s00112-009-2141-4

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