Research progress of differentiation of stem cells into islet-like cells

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1 Chinese Bulletin of Life Sciences Vol. 18, No. 1 Feb., (2006) Q813; R587.1 A Research progress of differentiation of stem cells into islet-like cells LU Yan, ZHANG Yuan* (Insititute of Hematology, Jinan University, Guangzhou , China) Abstract: The morbidity rate of diabetes mellitus is increasing at present, which is a serious disease damaging human being s health. The transplantation of pancreatic islet cells has been used to treat the diabetes type 1 and 2. However, it is necessary to search new sources of insulin-secreting cells for cell therapy of diabetes mellitus due to lacking of sufficient donor cells. With the development of cell therapy and tissue engineering in recent years, the new way of new islet cells from stem cells has be found, which can provide new islets for curing of diabetes. The progress of differentiation from stem cells into islet-like cells, problems and prospect will be discussed in the review. Key words: stem cell; diabetes mellitus; cell therapy 1 (diabetes mellitus DM) WHO % 2000 Shapiro [1] (Edmonton) [2] (2005) (1978 ) (1948 ) *

2 76 (embryonic stem cell, ESC) (adult stem cell, ASC) [3] ES Lumelsky [4] ES α β 40 1/50 (islet amyloid polypeptide) 2(glucose transporter2, GLUT2) 12 (1~ ) ES Assady [5] ES β ( GLUT2) 60%~70% (EBs) EBs 1%~3% Hori [6] LY294002( 3 ) LY DNA (insulin-producing cell cluster, IPCC) 10% 13% Rajagopal [7] ES β β Soria [8] /βgeo pgk-hygro ES (IB/3x-99) 16.5ng/µg( /µg ) (10 6 ) (transdifferentiation) [9] Zhang [10] (islet-like cell cluters, ICCs) 16 nestin (hepatocyte grow factor, HGF) A β exendin4 (nicotinamide, NIC) µiu/µg nestin CD44 CD90 CD147 CD34 CD38 CD45 CD71 CD117 CD133 HLA-DR Zalzman [11] Pdx-1 (pancreatic and duodenal homeobox 1) ITS 15

3 77 GLUT Ramiya [12] (NOD ) (islet-producing stem cell, IPCCs) ( 3 ) IPCCs NOD ( ADP- ) [13] β [14] NIC (epidermal growth factor, EGF) HGF 5 10 HGF HGF β β Bonner-Weir [15] (keratinocyte growth factor, KGF) Matrigel (cultured human islet buds, CHIB) Zulewski [16] nestin nestin (nestin-positive islet-derived progenitor cell, NIPs) NIPs CK-19 Pdx-1 HGF/activin A 2.5mM NIPs GLP-1 NIPs mrna Yang [17] mrna PDX-1 β Ferber [18] Pdx %~60% PDX-1 0.1%~1% 600mg/dL 200mg/dL Oh [19] 1% (DMSO) 3 10% (FBS) 7 mrna 186ng/mL 80% C 10 Oh [19] Tang [20] [21~22] [17] exendin4 mrna 10%~20% 10%~20% C INS-1 IPGT 60~90min Tang [20] (1) Pdx-1 insulin β 20mM β ES 5mM

4 78 β (2) β exendin4 [23] bfgf HGF LY β (umbilical cord blood, UCB) (UCB) 1 2 [24~25] Ende [24] 2 1 [25] ( Matrigel ) β β Soria [8] β 3.2 ES (ASC) ES ES ES β Newport Green [26] ASC ES β Dor [27] β β β ASC ASC ES ASC ASC (1) (2) (3) (4)

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