Transplantation of mesenchymal stem cells recruits trophic macrophages to induce pancreatic beta cell regeneration in diabetic mice

被引:64
作者
Cao, Xiaocang [1 ]
Han, Zhi-Bo [2 ,3 ,4 ]
Zhao, Hui [5 ]
Liu, Qiang [4 ,6 ]
机构
[1] Tianjin Med Univ, Gen Hosp, Dept Gastroenterol & Hepatol, Tianjin, Peoples R China
[2] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China
[3] Chinese Acad Med Sci, Hosp Blood Dis, Tianjin, Peoples R China
[4] Peking Union Med Coll, Tianjin, Peoples R China
[5] Tianjin Univ Commerce, Sch Biotechnol & Food Sci, Tianjin Key Lab Food & Biotechnol, Tianjin, Peoples R China
[6] Chinese Acad Med Sci, Inst Radiat Med, Tianjin Key Lab Mol Nucl Med, Tianjin, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
Mesenchymal stem cells; Diabetes; M2; macrophages; SDF-1; Wnt3a; BONE-MARROW-CELLS; IN-VIVO; NO EVIDENCE; PROLIFERATION; FUSION; ACTIVATION; PLASTICITY; TRANSDIFFERENTIATION; MICROENVIRONMENT; NEUROGENIN3;
D O I
10.1016/j.biocel.2014.06.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alleviation of hyperglycemia in chemical-induced diabetic mice has been reported after bone marrow transplantation. Nevertheless, the underlying mechanism remains elusive. In the present study, we transplanted genetically labeled primary mouse mesenchymal stem cells into the pancreas of the streptozotocin-treated hyperglycemic isogeneic mice, resulting in a decrease in blood glucose due to a recovery in beta cell mass. Further analysis revealed that the increase in beta cell mass was predominantly attributable to beta cell replication. The grafted mesenchymal stem cells did not transdifferentiate into beta cells themselves but recruited and polarized macrophages in a Stromal cell-derived factor 1-dependent manner, which in turn promoted beta cell replication. Our finding thus suggests that transplantation of autogenic mesenchymal stem cells may increase functional beta cell mass by boosting beta cell replication in diabetes. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:372 / 379
页数:8
相关论文
共 44 条
[1]   A Novel Strategy to Increase the Proliferative Potential of Adult Human β-Cells While Maintaining Their Differentiated Phenotype [J].
Aly, Haytham ;
Rohatgi, Nidhi ;
Marshall, Connie A. ;
Grossenheider, Tiffani C. ;
Miyoshi, Hiroyuki ;
Stappenbeck, Thaddeus S. ;
Matkovich, Scot J. ;
McDaniel, Michael L. .
PLOS ONE, 2013, 8 (06)
[2]   A transient microenvironment loaded mainly with macrophages in the early developing human pancreas [J].
Banaei-Bouchareb, L ;
Peuchmaur, M ;
Czernichow, P ;
Polak, M .
JOURNAL OF ENDOCRINOLOGY, 2006, 188 (03) :467-480
[3]   Islet Microenvironment, Modulated by Vascular Endothelial Growth Factor-A Signaling, Promotes β Cell Regeneration [J].
Brissova, Marcela ;
Aamodt, Kristie ;
Brahmachary, Priyanka ;
Prasad, Nripesh ;
Hong, Ji-Young ;
Dai, Chunhua ;
Mellati, Mahnaz ;
Shostak, Alena ;
Poffenberger, Greg ;
Aramandla, Radhika ;
Levy, Shawn E. ;
Powers, Alvin C. .
CELL METABOLISM, 2014, 19 (03) :498-511
[4]   Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells [J].
Choi, JB ;
Uchino, H ;
Azuma, K ;
Iwashita, N ;
Tanaka, Y ;
Mochizuki, H ;
Migita, M ;
Shimada, T ;
Kawamori, R ;
Watada, H .
DIABETOLOGIA, 2003, 46 (10) :1366-1374
[5]   C-Peptide Levels and Insulin Independence Following Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus [J].
Couri, Carlos E. B. ;
Oliveira, Maria C. B. ;
Stracieri, Ana B. P. L. ;
Moraes, Daniela A. ;
Pieroni, Fabiano ;
Barros, George M. N. ;
Madeira, Maria Isabel A. ;
Malmegrim, Kelen C. R. ;
Foss-Freitas, Maria C. ;
Simoes, Belinda P. ;
Martinez, Edson Z. ;
Foss, Milton C. ;
Burt, Richard K. ;
Voltarelli, Julio C. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2009, 301 (15) :1573-1579
[6]   Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation [J].
Dor, Y ;
Brown, J ;
Martinez, OI ;
Melton, DA .
NATURE, 2004, 429 (6987) :41-46
[7]   β cell replication is the primary mechanism for maintaining postnatal β cell mass [J].
Georgia, S ;
Bhushan, A .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (07) :963-968
[8]   Macrophages in the murine pancreas and their involvement in fetal endocrine development in vitro [J].
Geutskens, SB ;
Otonkoski, T ;
Pulkkinen, MA ;
Drexhage, HA ;
Leenen, PJM .
JOURNAL OF LEUKOCYTE BIOLOGY, 2005, 78 (04) :845-852
[9]   Alternative activation of macrophages [J].
Gordon, S .
NATURE REVIEWS IMMUNOLOGY, 2003, 3 (01) :23-35
[10]   neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas [J].
Gradwohl, G ;
Dierich, A ;
LeMeur, M ;
Guillemot, F .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (04) :1607-1611