|
|
Blood, 15 December 2005, Vol. 106, No. 13, pp. 4057-4065.
Prepublished online as a Blood First Edition Paper on August 23, 2005; DOI 10.1182/blood-2005-03-1004.
 Previous Article | Table of Contents | Next Article 
GENE THERAPY
Allogeneic marrow stromal cells are immune rejected by MHC class I– and class II–mismatched recipient mice
Nicoletta Eliopoulos,
John Stagg,
Laurence Lejeune,
Sandra Pommey, and
Jacques Galipeau
From the Lady Davis Institute for Medical Research, McGill University, Montreal, QC; and the Division of Hematology/Oncology, Jewish General Hospital, McGill University, Montreal, QC.
It has been suggested that marrow stromal cells (MSCs) may be immunoprivileged and can engraft in allogeneic recipients with intact immune systems. We determined if the implantation of murine MSCs engineered to release erythropoietin (Epo) would be feasible in major histocompatibility complex (MHC)-mismatched allogeneic mice without immunosuppression, and we monitored hematocrit (Hct) as a reporter of MSC graft survival. MSCs from C57Bl/6 mice were engineered to release murine Epo (Epo+ MSCs) and implanted subcutaneously in either syngeneic C57Bl/6 mice or MHC-mismatched Balb/c mice. In syngeneic recipients, the Hct rapidly rose from baseline level and remained higher than .88 (88%) for more than 200 days. However, in MHC-mismatched recipient Balb/c mice, the Hct rose transiently and rapidly declined to baseline values. Repeat implantations in these same mice were associated with an acquired refractoriness in the Hct response consistent with alloimmunization to donor Epo+ MSCs. Allogeneic MSC implants had an increased proportion of host-derived lymphoid CD8+, natural killer T (NKT), and NK infiltrating cells compared with syngeneic controls, and splenocytes isolated from Balb/c mice that had received implants also displayed a significant interferon-gamma (IFN ) response to C57Bl/6 MSCs in vitro. These results strongly suggest that MSCs are not intrinsically immunoprivileged and cannot serve as a "universal donor" in immunocompetent MHC-mismatched recipients.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. Romieu-Mourez, M. Francois, M.-N. Boivin, M. Bouchentouf, D. E. Spaner, and J. Galipeau
Cytokine Modulation of TLR Expression and Activation in Mesenchymal Stromal Cells Leads to a Proinflammatory Phenotype
J. Immunol.,
June 15, 2009;
182(12):
7963 - 7973.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Rafei, P. M. Campeau, A. Aguilar-Mahecha, M. Buchanan, P. Williams, E. Birman, S. Yuan, Y. K. Young, M.-N. Boivin, K. Forner, et al.
Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Inhibiting CD4 Th17 T Cells in a CC Chemokine Ligand 2-Dependent Manner
J. Immunol.,
May 15, 2009;
182(10):
5994 - 6002.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Vela, G. V. Silva, J. A.R. Assad, A. L.S. Sousa, S. Coulter, M. R. Fernandes, E. C. Perin, J. T. Willerson, and L. M. Buja
Histopathological Study of Healing After Allogenic Mesenchymal Stem Cell Delivery in Myocardial Infarction in Dogs
J. Histochem. Cytochem.,
February 1, 2009;
57(2):
167 - 176.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Walker, S. K. Shah, M. T. Harting, and C. S. Cox Jr
Progenitor cell therapies for traumatic brain injury: barriers and opportunities in translation
Dis. Model. Mech.,
January 1, 2009;
2(1-2):
23 - 38.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Rafei, J. Hsieh, S. Fortier, M. Li, S. Yuan, E. Birman, K. Forner, M.-N. Boivin, K. Doody, M. Tremblay, et al.
Mesenchymal stromal cell-derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction
Blood,
December 15, 2008;
112(13):
4991 - 4998.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Atoui, D. Shum-Tim, and R. C.J. Chiu
Myocardial Regenerative Therapy: Immunologic Basis for the Potential "Universal Donor Cells"
Ann. Thorac. Surg.,
July 1, 2008;
86(1):
327 - 334.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Coutu, J. H. Wu, A. Monette, G.-E. Rivard, M. D. Blostein, and J. Galipeau
Periostin, a Member of a Novel Family of Vitamin K-dependent Proteins, Is Expressed by Mesenchymal Stromal Cells
J. Biol. Chem.,
June 27, 2008;
283(26):
17991 - 18001.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Eliopoulos, M. Francois, M.-N. Boivin, D. Martineau, and J. Galipeau
Neo-Organoid of Marrow Mesenchymal Stromal Cells Secreting Interleukin-12 for Breast Cancer Therapy
Cancer Res.,
June 15, 2008;
68(12):
4810 - 4818.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Morandi, L. Raffaghello, G. Bianchi, F. Meloni, A. Salis, E. Millo, S. Ferrone, V. Barnaba, and V. Pistoia
Immunogenicity of Human Mesenchymal Stem Cells in HLA-Class I-Restricted T-Cell Responses Against Viral or Tumor-Associated Antigens
Stem Cells,
May 1, 2008;
26(5):
1275 - 1287.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. A. Sadek and D. J. Garry
Letter by Sadek and Garry Regarding Article, "Iron-Oxide Labeling and Outcome of Transplanted Mesenchymal Stem Cells in the Infarcted Myocardium"
Circulation,
April 8, 2008;
117(14):
e306 - e306.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Nauta and W. E. Fibbe
Immunomodulatory properties of mesenchymal stromal cells
Blood,
November 15, 2007;
110(10):
3499 - 3506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Rasmusson, M. Uhlin, K. Le Blanc, and V. Levitsky
Mesenchymal stem cells fail to trigger effector functions of cytotoxic T lymphocytes
J. Leukoc. Biol.,
October 1, 2007;
82(4):
887 - 893.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Gieseke, B. Schutt, S. Viebahn, E. Koscielniak, W. Friedrich, R. Handgretinger, and I. Muller
Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFN{gamma}R1 signaling and IDO expression
Blood,
September 15, 2007;
110(6):
2197 - 2200.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Sundin, O. Ringden, B. Sundberg, S. Nava, C. Gotherstrom, and K. Le Blanc
No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients
Haematologica,
September 1, 2007;
92(9):
1208 - 1215.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Batten, N. A Rosenthal, and M. H Yacoub
Immune response to stem cells and strategies to induce tolerance
Phil Trans R Soc B,
August 29, 2007;
362(1484):
1343 - 1356.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Cahill, D. Wenkert, S. A. Perlman, A. Steele, S. P. Coburn, W. H. McAlister, S. Mumm, and M. P. Whyte
Infantile Hypophosphatasia: Transplantation Therapy Trial Using Bone Fragments and Cultured Osteoblasts
J. Clin. Endocrinol. Metab.,
August 1, 2007;
92(8):
2923 - 2930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Romieu-Mourez, M. Francois, M.-N. Boivin, J. Stagg, and J. Galipeau
Regulation of MHC Class II Expression and Antigen Processing in Murine and Human Mesenchymal Stromal Cells by IFN-{gamma}, TGF-beta, and Cell Density
J. Immunol.,
August 1, 2007;
179(3):
1549 - 1558.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Locatelli, R. Maccario, and F. Frassoni
Mesenchymal stromal cells, from indifferent spectators to principal actors. Are we going to witness a revolution in the scenario of allograft and immune-mediated disorders?
Haematologica,
July 1, 2007;
92(7):
872 - 877.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Benvenuto, S. Ferrari, E. Gerdoni, F. Gualandi, F. Frassoni, V. Pistoia, G. Mancardi, and A. Uccelli
Human Mesenchymal Stem Cells Promote Survival of T Cells in a Quiescent State
Stem Cells,
July 1, 2007;
25(7):
1753 - 1760.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Campbell, T. H. Fischer, and A. S. Wolberg
A Novel Use of Rehydrated, Lyophilized Platelets Increases Recombinant FVIIa Procoagulant Activity in a Model of Hemophilia.
Blood (ASH Annual Meeting Abstracts),
November 16, 2006;
108(11):
1754 - 1754.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. A. Gregory, E. Reyes, M. J. Whitney, and J. L. Spees
Enhanced Engraftment of Mesenchymal Stem Cells in a Cutaneous Wound Model by Culture in Allogenic Species-Specific Serum and Administration in Fibrin Constructs
Stem Cells,
October 1, 2006;
24(10):
2232 - 2243.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Nauta, G. Westerhuis, A. B. Kruisselbrink, E. G. A. Lurvink, R. Willemze, and W. E. Fibbe
Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting
Blood,
September 15, 2006;
108(6):
2114 - 2120.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Sudres, F. Norol, A. Trenado, S. Gregoire, F. Charlotte, B. Levacher, J.-J. Lataillade, P. Bourin, X. Holy, J.-P. Vernant, et al.
Bone Marrow Mesenchymal Stem Cells Suppress Lymphocyte Proliferation In Vitro but Fail to Prevent Graft-versus-Host Disease in Mice.
J. Immunol.,
June 15, 2006;
176(12):
7761 - 7767.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Chan, K. C. Tang, A. P. Patel, L. M. Bonilla, N. Pierobon, N. M. Ponzio, and P. Rameshwar
Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-{gamma}
Blood,
June 15, 2006;
107(12):
4817 - 4824.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Eliopoulos, R. F. Gagnon, M. Francois, and J. Galipeau
Erythropoietin Delivery by Genetically Engineered Bone Marrow Stromal Cells for Correction of Anemia in Mice with Chronic Renal Failure
J. Am. Soc. Nephrol.,
June 1, 2006;
17(6):
1576 - 1584.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Gangadharan, E. T. Parker, L. M. Ide, H. T. Spencer, and C. B. Doering
High-level expression of porcine factor VIII from genetically modified bone marrow-derived stem cells
Blood,
May 15, 2006;
107(10):
3859 - 3864.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
