Preserved β-Cell Function in Type 1 Diabetes by Mesenchymal Stromal Cells

被引:229
作者
Carlsson, Per-Ola [1 ,2 ]
Schwarcz, Erik [3 ]
Korsgren, Olle [4 ]
Le Blanc, Katarina [5 ]
机构
[1] Uppsala Univ, Dept Med Cell Biol, Uppsala, Sweden
[2] Uppsala Univ, Dept Med Sci, Uppsala, Sweden
[3] Orebro Univ Hosp, Dept Internal Med, Orebro, Sweden
[4] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden
[5] Karolinska Inst, Dept Lab Med, Stockholm, Sweden
基金
瑞典研究理事会;
关键词
VERSUS-HOST-DISEASE; STEM-CELLS; COMPLICATIONS; THERAPY; TRIAL;
D O I
10.2337/db14-0656
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The retention of endogenous insulin secretion in type 1 diabetes is an attractive clinical goal, which opens possibilities for long-term restoration of glucose metabolism. Mesenchymal stromal cells (MSCs) constitute, based on animal studies, a promising interventional strategy for the disease. This prospective clinical study describes the translation of this cellular intervention strategy to patients with recent-onset type 1 diabetes. Twenty adult patients with newly diagnosed type 1 diabetes were enrolled and randomized to MSC treatment or to the control group. Residual beta-cell function was analyzed as C-peptide concentrations in blood in response to a mixed-meal tolerance test (MMTT) at 1-year follow-up. In contrast to the patients in the control arm, who showed loss in both C-peptide peak values and C-peptide when calculated as area under the curve during the 1st year, these responses were preserved or even increased in the MSC-treated patients. Importantly, no side effects of MSC treatment were observed. We conclude that autologous MSC treatment in new-onset type 1 diabetes constitutes a safe and promising strategy to intervene in disease progression and preserve beta-cell function.
引用
收藏
页码:587 / 592
页数:6
相关论文
共 26 条
[1]   Immunomodulation by mesenchymal stem cells - A potential therapeutic strategy for type 1 diabetes [J].
Abdi, Reza ;
Fiorina, Paolo ;
Adra, Chaker N. ;
Atkinson, Mark ;
Sayegh, Mohamed H. .
DIABETES, 2008, 57 (07) :1759-1767
[2]  
Bonfanti R, 1998, DIABETIC MED, V15, P844, DOI 10.1002/(SICI)1096-9136(199810)15:10<844::AID-DIA679>3.0.CO
[3]  
2-A
[4]   A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells [J].
Chabannes, Dominique ;
Hill, Marcelo ;
Merieau, Emmanuel ;
Rossignol, Julien ;
Brion, Regis ;
Soulillou, Jean Paul ;
Anegon, Ignacio ;
Cuturi, Maria Cristina .
BLOOD, 2007, 110 (10) :3691-3694
[5]   Persistent High Glucose Concentrations Alter the Regenerative Potential of Mesenchymal Stem Cells [J].
Cramer, Christopher ;
Freisinger, Eva ;
Jones, Ryan K. ;
Slakey, Douglas P. ;
Dupin, Charles L. ;
Newsome, Edward R. ;
Alt, Eckhard U. ;
Izadpanah, Reza .
STEM CELLS AND DEVELOPMENT, 2010, 19 (12) :1875-1884
[6]   Clinical evolution of beta cell function in youth with diabetes: the SEARCH for Diabetes in Youth study [J].
Dabelea, D. ;
Mayer-Davis, E. J. ;
Andrews, J. S. ;
Dolan, L. M. ;
Pihoker, C. ;
Hamman, R. F. ;
Greenbaum, C. ;
Marcovina, S. ;
Fujimoto, W. ;
Linder, B. ;
Imperatore, G. ;
D'Agostino, R., Jr. .
DIABETOLOGIA, 2012, 55 (12) :3359-3368
[7]   Mesenchymal cells recruit and regulate T regulatory cells [J].
Di Lanni, Mauro ;
Del Papa, Beatrice ;
De Loanni, Maria ;
Moretti, Lorenzo ;
Bonifacio, Elisabetta ;
Cecchini, Debora ;
Sportoletti, Paolo ;
Falzetti, Franca ;
Tabilio, Antonio .
EXPERIMENTAL HEMATOLOGY, 2008, 36 (03) :309-318
[8]   Mesenchymal stem cells in tissue repair [J].
DiMarino, Amy M. ;
Caplan, Arnold I. ;
Bonfield, Tracey L. .
FRONTIERS IN IMMUNOLOGY, 2013, 4
[9]   Mesenchymal Stem Cells Prevent the Rejection of Fully Allogenic Islet Grafts by the Immunosuppressive Activity of Matrix Metalloproteinase-2 and-9 [J].
Ding, Yunchuan ;
Xu, Danmei ;
Feng, Gang ;
Bushell, Andrew ;
Muschel, Ruth J. ;
Wood, Kathryn J. .
DIABETES, 2009, 58 (08) :1797-1806
[10]   Immunomodulatory Function of Bone Marrow-Derived Mesenchymal Stem Cells in Experimental Autoimmune Type 1 Diabetes [J].
Fiorina, Paolo ;
Jurewicz, Mollie ;
Augello, Andrea ;
Vergani, Andrea ;
Dada, Shirine ;
La Rosa, Stefano ;
Selig, Martin ;
Godwin, Jonathan ;
Law, Kenneth ;
Placidi, Claudia ;
Smith, R. Neal ;
Capella, Carlo ;
Rodig, Scott ;
Adra, Chaker N. ;
Atkinson, Mark ;
Sayegh, Mohamed H. ;
Abdi, Reza .
JOURNAL OF IMMUNOLOGY, 2009, 183 (02) :993-1004