Mesenchymal Stromal Cells: a New Tool Against Graft-versus-host Disease?

Overview

Journal Biol Blood Marrow Transplant

Date 2011 Oct 4

PMID 21963621

Citations 48

Authors

Frederic Baron

Rainer Storb

Affiliations

Soon will be listed here.

Abstract

Mesenchymal stromal cells (MSCs) represent a heterogeneous subset of multipotent cells that can be isolated from several tissues including bone marrow and fat. MSCs exhibit immunomodulatory and anti-inflammatory properties that prompted their clinical use as prevention and/or treatment for severe graft-versus-host disease (GVHD). Although a number of phase I-II studies have suggested that MSC infusion was safe and might be effective for preventing or treating acute GVHD, definitive proof of their efficacy remains lacking thus far. Multicenter randomized studies are ongoing to more precisely assess the impact of MSC infusion on GVHD prevention/treatment, whereas further research is performed in vitro and in animal models with the aims of determining the best way to expand MSCs ex vivo as well as the most efficient dose and schedule of MSCs administration. After introducing GVHD, MSC biology, and results of MSC infusion in animal models of allogeneic hematopoietic cell transplantation, this article reviews the results of the first clinical trials investigating the use of MSC infusion as prevention or treatment of GVHD.

Citing Articles

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References

Flowers M, Leisenring W, Beach K, Riddell S, Radich J, Higano C . Granulocyte colony-stimulating factor given to donors before apheresis does not prevent aplasia in patients treated with donor leukocyte infusion for recurrent chronic myeloid leukemia after bone marrow transplantation. Biol Blood Marrow Transplant. 2000; 6(3A):321-6. DOI: 10.1016/s1083-8791(00)70057-7. View

Kolb H, Schmid C, Barrett A, Schendel D . Graft-versus-leukemia reactions in allogeneic chimeras. Blood. 2003; 103(3):767-76. DOI: 10.1182/blood-2003-02-0342. View

Spaeth E, Klopp A, Dembinski J, Andreeff M, Marini F . Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther. 2008; 15(10):730-8. DOI: 10.1038/gt.2008.39. View

Simmons P, Przepiorka D, Thomas E, Torok-Storb B . Host origin of marrow stromal cells following allogeneic bone marrow transplantation. Nature. 1987; 328(6129):429-32. DOI: 10.1038/328429a0. View

Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E . IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol. 2008; 38(6):1745-55. PMC: 3021120. DOI: 10.1002/eji.200738129. View

FRIEDENSTEIN A, PETRAKOVA K, Kurolesova A, Frolova G . Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 1968; 6(2):230-47. View

Wolff D, Gerbitz A, Ayuk F, Kiani A, Hildebrandt G, Vogelsang G . Consensus conference on clinical practice in chronic graft-versus-host disease (GVHD): first-line and topical treatment of chronic GVHD. Biol Blood Marrow Transplant. 2010; 16(12):1611-28. DOI: 10.1016/j.bbmt.2010.06.015. View

Spaggiari G, Abdelrazik H, Becchetti F, Moretta L . MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2. Blood. 2009; 113(26):6576-83. DOI: 10.1182/blood-2009-02-203943. View

Allison M . Genzyme backs Osiris, despite Prochymal flop. Nat Biotechnol. 2009; 27(11):966-7. DOI: 10.1038/nbt1109-966. View

10.

Mougiakakos D, Jitschin R, Johansson C, Okita R, Kiessling R, Le Blanc K . The impact of inflammatory licensing on heme oxygenase-1-mediated induction of regulatory T cells by human mesenchymal stem cells. Blood. 2011; 117(18):4826-35. DOI: 10.1182/blood-2010-12-324038. View

11.

Wynn R, Hart C, Corradi-Perini C, ONeill L, Evans C, Wraith J . A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood. 2004; 104(9):2643-5. DOI: 10.1182/blood-2004-02-0526. View

12.

Awaya N, Rupert K, Bryant E, Torok-Storb B . Failure of adult marrow-derived stem cells to generate marrow stroma after successful hematopoietic stem cell transplantation. Exp Hematol. 2002; 30(8):937-42. DOI: 10.1016/s0301-472x(02)00821-4. View

13.

Paczesny S, Levine J, Braun T, Ferrara J . Plasma biomarkers in graft-versus-host disease: a new era?. Biol Blood Marrow Transplant. 2009; 15(1 Suppl):33-8. PMC: 2644447. DOI: 10.1016/j.bbmt.2008.10.027. View

14.

Goldman J, Gale R, Horowitz M, BIGGS J, Champlin R, Gluckman E . Bone marrow transplantation for chronic myelogenous leukemia in chronic phase. Increased risk for relapse associated with T-cell depletion. Ann Intern Med. 1988; 108(6):806-14. DOI: 10.7326/0003-4819-108-6-806. View

15.

Randolph S, Gooley T, Warren E, Appelbaum F, Riddell S . Female donors contribute to a selective graft-versus-leukemia effect in male recipients of HLA-matched, related hematopoietic stem cell transplants. Blood. 2003; 103(1):347-52. DOI: 10.1182/blood-2003-07-2603. View

16.

Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, CIVIDALLI G . Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998; 91(3):756-63. View

17.

Baron F, Sandmaier B, Zellmer E, Sorror M, Storer B, Storb R . Failure of donor lymphocyte infusion to prevent graft rejection in dogs given DLA-identical marrow after 1 Gy of total body irradiation. Biol Blood Marrow Transplant. 2006; 12(8):813-7. DOI: 10.1016/j.bbmt.2006.05.001. View

18.

Mouiseddine M, Francois S, Semont A, Sache A, Allenet B, Mathieu N . Human mesenchymal stem cells home specifically to radiation-injured tissues in a non-obese diabetes/severe combined immunodeficiency mouse model. Br J Radiol. 2007; 80 Spec No 1:S49-55. DOI: 10.1259/bjr/25927054. View

19.

. Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol. 2005; 23(22):5074-87. PMC: 1475795. DOI: 10.1200/JCO.2005.09.020. View

20.

Lee W, Suzuki Y, Graves S, Iwata M, Venkataraman G, Mielcarek M . Canine bone marrow-derived mesenchymal stromal cells suppress alloreactive lymphocyte proliferation in vitro but fail to enhance engraftment in canine bone marrow transplantation. Biol Blood Marrow Transplant. 2010; 17(4):465-75. PMC: 3233364. DOI: 10.1016/j.bbmt.2010.04.016. View