Advancements of stem-cell therapy for type 1 diabetes mellitus

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1 Chinese Bulletin of Life Sciences Vol. 19, No. 4 Aug., (2007) ( ) 1 β β 1 1 R58.71; Q813 A Advancements of stem-cell therapy for type 1 diabetes mellitus LI Hongdan, WEI Jia, MU Changzheng* (Liaoning Medical College, Jinzhou , China ) Abstract: Type 1 diabetes is characterized by the selective destruction of pancreatic β-cells caused by an autoimmune attack. Restoration of damaged β-cells by transplantation from exogenous sources or by endocrine pancreas regeneration would be ideal therapeutic options. Stem cells of both embryonic and adult origin offer some interesting alternatives, taking into account the latest advances indicating that these cells could be the potential building blocks from which insulin secreting cells could be obtained in vitro under appropriate culture conditions. Although it has been reported that insulin-producing cells derived from stem cells have been shown to reverse experimentally induced diabetes in animal models, several concerns need to be solved before finding a definite medical application. These refer mainly to the obtainment of a cell population as similar as possible to pancreatic β-cells, and to the problems related with the immune compatibility and tumor formation. This review will describe the different approaches that have been used to obtain insulin-producing cells from embryonic and adult stem cells, the effect of cell transplantation for treating type 1 diabetes mellitus and analyze the main problems of therapy with these stem cells and the possible solving methods. Key words: stem cell; induced differentiation; insulin secreting cells; type 1 diabetes mellitus; biological therapy 1 2 WHO (1981 ) (1962 ) * muchangzheng@yahoo.com.cn

2 Bonner- Weir [1] T T T NOD 1 T NOD [2] Mathis [3] T (antigen presenting cells APCs) (dendritic cell) APCs MHC T APCs β T MHC Pβ 2 β 10 [4] Shapiro [5] [6] (Edmonton protocol) (ESC) (ASC) ( 1) [7] 2.1 Lumelsky [8] β 1 2 1/50 Glut2 IAPP ( ) 12 d Assady [9] (hes) hes β β ( Glut2) 2002 Hori [10] LY ( 3 )

3 β [7] DNA Rajagopal [11] ES β β Hansson [12] os25 ( β Sox2 ) C C Vacap [13] ESD3 STZ C D Amour [14] C Fujikawa [15] Lumelsky [8] 30 d NOD/SCID β Chen [16] Wistar 10 mmol/l 1 mmol/l β DMEM 24 h 10 mmol/l 1 mmol/l β 10 h mrna STZ

4 Oh [17] 1% DMSO 3 d 10% FBS 7 d mrna 186 ng/ml 80% C STZ NOD/SCID Tang [18] Balb/c 10% FCS RPMI (5.5 mmol/l) (5%) 10 mmol/l RPMI d 10 nmol/l exendin d C mrna ins-1 ins-2 Glut-2 GK pdx-1 Moriscot [19] pdx-1 β exendin-4 β [20] [21] bfgf HGF LY β Choi [22] Petersen [23] 1 h Lu [24] Lee [25] Kim [26] C C β ( ) 1 Ianus [27] 1 2 β Y β Hess [28] STZ (GFP) 17 d 42 d 75% 85% 42 d 0% 50% c-kit c-kit (UCB) [29-30] Ende [29] 2 1

5 [30] Sun [31] SSEA-4 OCT-4 DMEM/F12 10 mmol/l 20 nmol/l 100 mol/l 1 g/ml 25 g/ml 30 mol/l 50 g/ml 5 g/ml B27 (1 50) 15% FBS 24 h DMEM DMEM/F d C Zhang [32] 16 nestin α β exendin-4 nestin CD44 CD90 CD147 CD34 CD38 CD45 CD71 CD117 CD133 HLA-DR β α δ γ Bouwens [33] Cossel [34] Dudek [35] Bonner- Weir [1] 2007 Koblas [36] CXCR4 CXCR Yang [37] mrna Timper [38] ( 1)

6 ( ) bfgf exendin-4 (1) (2) RT- PCR C Glut-1 Glut-2 GK IAPP nestin β PDX-1 PAX-6 PAX-4 OCT-4 C C β C C (1) 1 (2) (3) NO

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