人脐带Wharton’s Jelly中间充质干细胞对1型糖尿病大鼠血糖及体重的影响
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摘要
目的:前期实验利用胰岛细胞生存的微环境已经将人脐带Wharton’s Jelly中间充质干细胞(hUC-MSCs)诱导分化为具有胰岛素分泌功能的胰岛样细胞,但是这些诱导分化的胰岛样细胞在体内的功能如何尚不确定。本实验旨在观察hUC-MSCs诱导分化的胰岛样细胞对1型糖尿病大鼠血糖及体重的影响。
方法:
1采用组织块贴壁法分离培养hUC-MSCs ;
2利用胶原酶ⅴ分次消化大鼠胰岛细胞;
3应用Transwell板将hUC-MSCs与大鼠胰岛细胞共培养,利用胰岛细胞生存的微环境将hUC-MSCs向胰岛样细胞诱导分化,倒置显微镜下观察细胞形态变化;
4将SD大鼠随机分为正常对照组和糖尿病模型组。腹腔注射链脲佐菌素(STZ)制作1型糖尿病大鼠模型,随机血糖连续3次>16.7mmol/L定为糖尿病大鼠造模成功。将造模成功的糖尿病大鼠随机分为两组:STZ实验组(糖尿病大鼠肾被膜下移植诱导后的胰岛样细胞)和STZ对照组(糖尿病大鼠不做任何处理);
5在移植前应用Brdu对诱导后的胰岛样细胞进行标记;
6将Brdu标记后的胰岛样细胞移植到STZ实验组糖尿病大鼠的肾被膜下,观察大鼠血糖、体重的变化,8周后结束实验。
7实验结束时将大鼠的胰腺和肾脏摘除,胰腺行HE染色,肾脏行HE染色和免疫组化染色。
结果:
1腹腔注射STZ后大鼠的血糖明显升高,出现多尿、多饮、体重增加缓慢甚至降低,皮毛颜色暗淡,有脱毛现象。随机血糖连续3次>16.7mmol/L定为糖尿病大鼠造模成功,造模成功率为100%。
2在250倍镜下随机选取10个视野计数阳性细胞数与非阳性细胞数,计算Brdu阳性率=阳性细胞数/(阳性细胞数+非阳性细胞数),得出Brdu的标记率为92%。
3在实验过程中,STZ实验组有5只大鼠死亡(2只死于手术,3只死于高血糖),STZ对照组有8只大鼠死亡(均死于高血糖),最后进行统计分析的共17只(正常对照组6只,STZ实验组7只,STZ对照组4只)。
4大鼠血糖的变化细胞移植后8周,STZ实验组的血糖较移植前下降,差异具有统计学意义(p<0.05)。STZ对照组和正常对照组的血糖与移植前比较无明显差异(p>0.05)。STZ实验组的血糖移植前为(29.00±3.68)mmol/L,移植后为(20.31±1.70)mmol/L;STZ对照组的血糖实验前为(27.87±2.28)mmol/L,实验后为(28.23±1.89)mmol/L;正常对照组的血糖实验前为(6.70±0.25)mmol/L,实验后为(6.58±0.66)mmol/L。
5大鼠体重的变化细胞移植后8周,三组大鼠的体重较移植前均增加,差异均具有统计学意义(p<0.05)。正常对照组增加的最多,STZ实验组次之,STZ对照组增加的最少,差异具有统计学意义(p<0.05)。STZ实验组的体重移植前为(219.33±16.58)g,移植后为(323.14±28.33)g;STZ对照组的体重实验前为(207.25±13.63)g,实验后为(246.00±27.54)g;正常对照组的体重实验前为(275.33±28.49)g,实验后为(496.50±20.51)g。
6胰腺HE染色示:正常对照组大鼠的胰腺内散在分布大小不等、形状规则的胰岛,胰岛的结构清晰。STZ对照组糖尿病大鼠的胰岛数量明显减少,形状不规则,萎缩胰岛周围腺泡细胞肥大。胰腺间质大动脉收缩状,内皮细胞突向管腔,动脉壁增厚,动脉周围纤维组织增生,可见神经纤维束。胰腺小叶萎缩,腺泡腔明显,间质淋巴细胞浸润。STZ实验组大鼠的胰腺组织与STZ对照组有相似的改变,无自发恢复现象。
7肾脏HE染色示:正常对照组和STZ对照组大鼠的肾被膜边缘完整,形态清楚。STZ实验组大鼠在移植细胞的部位肾被膜和肾皮质之间有大量的细胞,部分肾被膜出现断裂现象。
8肾脏免疫组化染色示:正常对照组和STZ对照组大鼠的肾被膜下无胰岛素、Brdu染色阳性的细胞。STZ实验组大鼠在移植细胞的部位肾被膜和肾皮质之间有胰岛素、Brdu阳性的细胞。
结论:人脐带Wharton’s Jelly中的间充质干细胞与大鼠胰岛细胞共培养诱导分化的胰岛样细胞移植到糖尿病大鼠肾被膜下可在局部存活,并且能够使大鼠的血糖降低、体重增加。
OBJECTIVE: Mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord (hUC-MSCs) had been transdifferentiated into islet-like cells utilizing the microenvironment that islet cells living on the protophase. But it was unknown that if these islet-like cells could react in vivo. This study was to explore the effect of these islet-like cells on the levels of blood glucose and body weight in rats with type 1 Diabetic Mellitus (DM).
METHODS:
1 MSCs were isolated and cultured from Wharton’s Jelly of the human umbilical cord by tissue adherence.
2 The islet cells were isolated from pancreas by collagenase V digesting.
3 hUC-MSCs were induced by cocultureing with islet cells. Cell morphologic change was observed under inverted microscope.
4 Rats were divided into normal control group and diabetic model group. The models of type 1 DM were made by intraperitoneal injection streptozocin(STZ). If random blood sugar of rats exceeded 16.7mmol/L for continuous three times, diabetic models were considered to succeed. The diabetic rats were divided into STZ experiment group and STZ control group.
5 Postinduced cells were marked by Brdu.
6 The positive cells for Brdu were transplanted into renal capsule of diabetic rats in STZ experiment group. Blood glucose and body weight of diabetic rats were observed.The experiment was ended after 8 weeks.
7 The pancreas and kidney were removaled to carry out HE or immunohistochemistry dyeing at the end of the experiment.
RESULTS:
1 Blood glucose of rats increased remarkably after intraperitoneal injection STZ. Rats occurred urorrhagia and polydipsia symptoms. Their body weight didn’t increase even cut down. The fur of diabetic rats were dim and some fur depilated. If random blood sugar of rats exceeded 16.7mmol/L for continuous three times, diabetic models were considered to succeed. The achievement ratio of diabetic models was 100 percent.
2 Selecting ten visual fields randomly to count positive cells and negative cells under the microscope. Then, to calculate the positive rate of Brdu. The positive rate of Brdu was 92 percent.
3 In the process of experiment, five rats died in STZ experiment group, two of which died of operation and three of which died of hyperglycemia. Eight rats died of hyperglycemia in STZ control group. There only had seventeen rats to carry out statistical analysis eventually.
4 The change of blood glucose At eight weeks after cell transplantation, blood glucose in STZ experiment group decreased, there had statistical significance(p<0.05). Blood glucose in STZ control group and normal control group all had no statistical significance(p>0.05). Blood glucose in STZ experiment group were (29.00±3.68) mmol/L before cells transplantation and (20.31±1.70) mmol/L after cells transplantation. Blood glucose in STZ control group were (27.87±2.28) mmol/L before cells transplantation and (28.23±1.89) mmol/L after cells transplantation. Blood glucose in normal control group were (6.70±0.25) mmol/L before cells transplantation and (6.58±0.66) mmol/L after cells transplantation.
5 The change of body weight At eight weeks after cell transplantation, body weight increased in three groups, there all had statistical significance (p<0.05). The increment of body weight in normal control group was most, the second was STZ experiment group. The increment of body weight in STZ control group was least. Blood glucose in normal control group were (275.33±28.49) g before cells transplantation and (496.50±20.51) g after cells transplantation. Body weight in STZ experiment group were (219.33±16.58) g before cells transplantation and (323.14±28.33) g after cells transplantation. Blood glucose in STZ control group were (207.25±13.63) g before cells transplantation and (246.00±27.54) g after cells transplantation.
6 The HE dyeing showed that inequality of size pancreatic islet diffused distribution in normal pancreas. Their structures were clear. The quantity of islet decreased in diabetic rats of STZ control group. Their shapes were rugosity. Some hypertrophic acinar cells surrounded emarcide islets. Some large arteries were contractus in the interstitium of pancreas. Endothelial cells faced to lumens and the artery walls were incrassate. The fibrous tissue surrounding artery hyperplasy and formed some nerve fiber bundles. The lobule of pancreas atrophy. There had evident acinar lumina and some lymphocytes infiltrate into interstitium. The pancreas in STZ experiment group had the similar change to STZ control group.
7 The HE dyeing showed that the verge of renal capsule was integrity and clear in normal control group and STZ control group. There had considerable cells between renal capsule and renal cortex in STZ experiment group. The renal capsule appeared break.
8 The immunohistochemistry dyeing showed that there didn’t have positive cells for insulin or Brdu below the renal capsule in normal control group and STZ control group. There had some positive cells for insulin whose endochylemas were brown as well as some positive cells for Brdu whose nucelus were brown between renal capsule and renal cortex in STZ experiment group.
CONCLUSION: Islet-like cells derived from mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord could survival below the renal capsule of diabetic rats. These islet-like cells could lower blood glucose and increase body weight after cell transplantation.
方法:
1采用组织块贴壁法分离培养hUC-MSCs ;
2利用胶原酶ⅴ分次消化大鼠胰岛细胞;
3应用Transwell板将hUC-MSCs与大鼠胰岛细胞共培养,利用胰岛细胞生存的微环境将hUC-MSCs向胰岛样细胞诱导分化,倒置显微镜下观察细胞形态变化;
4将SD大鼠随机分为正常对照组和糖尿病模型组。腹腔注射链脲佐菌素(STZ)制作1型糖尿病大鼠模型,随机血糖连续3次>16.7mmol/L定为糖尿病大鼠造模成功。将造模成功的糖尿病大鼠随机分为两组:STZ实验组(糖尿病大鼠肾被膜下移植诱导后的胰岛样细胞)和STZ对照组(糖尿病大鼠不做任何处理);
5在移植前应用Brdu对诱导后的胰岛样细胞进行标记;
6将Brdu标记后的胰岛样细胞移植到STZ实验组糖尿病大鼠的肾被膜下,观察大鼠血糖、体重的变化,8周后结束实验。
7实验结束时将大鼠的胰腺和肾脏摘除,胰腺行HE染色,肾脏行HE染色和免疫组化染色。
结果:
1腹腔注射STZ后大鼠的血糖明显升高,出现多尿、多饮、体重增加缓慢甚至降低,皮毛颜色暗淡,有脱毛现象。随机血糖连续3次>16.7mmol/L定为糖尿病大鼠造模成功,造模成功率为100%。
2在250倍镜下随机选取10个视野计数阳性细胞数与非阳性细胞数,计算Brdu阳性率=阳性细胞数/(阳性细胞数+非阳性细胞数),得出Brdu的标记率为92%。
3在实验过程中,STZ实验组有5只大鼠死亡(2只死于手术,3只死于高血糖),STZ对照组有8只大鼠死亡(均死于高血糖),最后进行统计分析的共17只(正常对照组6只,STZ实验组7只,STZ对照组4只)。
4大鼠血糖的变化细胞移植后8周,STZ实验组的血糖较移植前下降,差异具有统计学意义(p<0.05)。STZ对照组和正常对照组的血糖与移植前比较无明显差异(p>0.05)。STZ实验组的血糖移植前为(29.00±3.68)mmol/L,移植后为(20.31±1.70)mmol/L;STZ对照组的血糖实验前为(27.87±2.28)mmol/L,实验后为(28.23±1.89)mmol/L;正常对照组的血糖实验前为(6.70±0.25)mmol/L,实验后为(6.58±0.66)mmol/L。
5大鼠体重的变化细胞移植后8周,三组大鼠的体重较移植前均增加,差异均具有统计学意义(p<0.05)。正常对照组增加的最多,STZ实验组次之,STZ对照组增加的最少,差异具有统计学意义(p<0.05)。STZ实验组的体重移植前为(219.33±16.58)g,移植后为(323.14±28.33)g;STZ对照组的体重实验前为(207.25±13.63)g,实验后为(246.00±27.54)g;正常对照组的体重实验前为(275.33±28.49)g,实验后为(496.50±20.51)g。
6胰腺HE染色示:正常对照组大鼠的胰腺内散在分布大小不等、形状规则的胰岛,胰岛的结构清晰。STZ对照组糖尿病大鼠的胰岛数量明显减少,形状不规则,萎缩胰岛周围腺泡细胞肥大。胰腺间质大动脉收缩状,内皮细胞突向管腔,动脉壁增厚,动脉周围纤维组织增生,可见神经纤维束。胰腺小叶萎缩,腺泡腔明显,间质淋巴细胞浸润。STZ实验组大鼠的胰腺组织与STZ对照组有相似的改变,无自发恢复现象。
7肾脏HE染色示:正常对照组和STZ对照组大鼠的肾被膜边缘完整,形态清楚。STZ实验组大鼠在移植细胞的部位肾被膜和肾皮质之间有大量的细胞,部分肾被膜出现断裂现象。
8肾脏免疫组化染色示:正常对照组和STZ对照组大鼠的肾被膜下无胰岛素、Brdu染色阳性的细胞。STZ实验组大鼠在移植细胞的部位肾被膜和肾皮质之间有胰岛素、Brdu阳性的细胞。
结论:人脐带Wharton’s Jelly中的间充质干细胞与大鼠胰岛细胞共培养诱导分化的胰岛样细胞移植到糖尿病大鼠肾被膜下可在局部存活,并且能够使大鼠的血糖降低、体重增加。
OBJECTIVE: Mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord (hUC-MSCs) had been transdifferentiated into islet-like cells utilizing the microenvironment that islet cells living on the protophase. But it was unknown that if these islet-like cells could react in vivo. This study was to explore the effect of these islet-like cells on the levels of blood glucose and body weight in rats with type 1 Diabetic Mellitus (DM).
METHODS:
1 MSCs were isolated and cultured from Wharton’s Jelly of the human umbilical cord by tissue adherence.
2 The islet cells were isolated from pancreas by collagenase V digesting.
3 hUC-MSCs were induced by cocultureing with islet cells. Cell morphologic change was observed under inverted microscope.
4 Rats were divided into normal control group and diabetic model group. The models of type 1 DM were made by intraperitoneal injection streptozocin(STZ). If random blood sugar of rats exceeded 16.7mmol/L for continuous three times, diabetic models were considered to succeed. The diabetic rats were divided into STZ experiment group and STZ control group.
5 Postinduced cells were marked by Brdu.
6 The positive cells for Brdu were transplanted into renal capsule of diabetic rats in STZ experiment group. Blood glucose and body weight of diabetic rats were observed.The experiment was ended after 8 weeks.
7 The pancreas and kidney were removaled to carry out HE or immunohistochemistry dyeing at the end of the experiment.
RESULTS:
1 Blood glucose of rats increased remarkably after intraperitoneal injection STZ. Rats occurred urorrhagia and polydipsia symptoms. Their body weight didn’t increase even cut down. The fur of diabetic rats were dim and some fur depilated. If random blood sugar of rats exceeded 16.7mmol/L for continuous three times, diabetic models were considered to succeed. The achievement ratio of diabetic models was 100 percent.
2 Selecting ten visual fields randomly to count positive cells and negative cells under the microscope. Then, to calculate the positive rate of Brdu. The positive rate of Brdu was 92 percent.
3 In the process of experiment, five rats died in STZ experiment group, two of which died of operation and three of which died of hyperglycemia. Eight rats died of hyperglycemia in STZ control group. There only had seventeen rats to carry out statistical analysis eventually.
4 The change of blood glucose At eight weeks after cell transplantation, blood glucose in STZ experiment group decreased, there had statistical significance(p<0.05). Blood glucose in STZ control group and normal control group all had no statistical significance(p>0.05). Blood glucose in STZ experiment group were (29.00±3.68) mmol/L before cells transplantation and (20.31±1.70) mmol/L after cells transplantation. Blood glucose in STZ control group were (27.87±2.28) mmol/L before cells transplantation and (28.23±1.89) mmol/L after cells transplantation. Blood glucose in normal control group were (6.70±0.25) mmol/L before cells transplantation and (6.58±0.66) mmol/L after cells transplantation.
5 The change of body weight At eight weeks after cell transplantation, body weight increased in three groups, there all had statistical significance (p<0.05). The increment of body weight in normal control group was most, the second was STZ experiment group. The increment of body weight in STZ control group was least. Blood glucose in normal control group were (275.33±28.49) g before cells transplantation and (496.50±20.51) g after cells transplantation. Body weight in STZ experiment group were (219.33±16.58) g before cells transplantation and (323.14±28.33) g after cells transplantation. Blood glucose in STZ control group were (207.25±13.63) g before cells transplantation and (246.00±27.54) g after cells transplantation.
6 The HE dyeing showed that inequality of size pancreatic islet diffused distribution in normal pancreas. Their structures were clear. The quantity of islet decreased in diabetic rats of STZ control group. Their shapes were rugosity. Some hypertrophic acinar cells surrounded emarcide islets. Some large arteries were contractus in the interstitium of pancreas. Endothelial cells faced to lumens and the artery walls were incrassate. The fibrous tissue surrounding artery hyperplasy and formed some nerve fiber bundles. The lobule of pancreas atrophy. There had evident acinar lumina and some lymphocytes infiltrate into interstitium. The pancreas in STZ experiment group had the similar change to STZ control group.
7 The HE dyeing showed that the verge of renal capsule was integrity and clear in normal control group and STZ control group. There had considerable cells between renal capsule and renal cortex in STZ experiment group. The renal capsule appeared break.
8 The immunohistochemistry dyeing showed that there didn’t have positive cells for insulin or Brdu below the renal capsule in normal control group and STZ control group. There had some positive cells for insulin whose endochylemas were brown as well as some positive cells for Brdu whose nucelus were brown between renal capsule and renal cortex in STZ experiment group.
CONCLUSION: Islet-like cells derived from mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord could survival below the renal capsule of diabetic rats. These islet-like cells could lower blood glucose and increase body weight after cell transplantation.
引文
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21余卫,何冬梅,张洹.胎肝间充质干细胞治疗实验性糖尿病小鼠的研究[J].暨南大学学报(医学版).2007, 28(6): 558-561
22 Tateishi K, He J, Taranova O, et al. Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem. 2008, 283(46): 31601-31607
23 Lee J, Han DJ, Kim SC. In vitro differentiation of human adipose tissue-derived stem cells into cells with pancreatic phenotype by regenerating pancreas extract. Biochem Biophys Res Commun. 2008, 375(4): 547-551
24 Timper K, Seboek D, Eberhardt M, et al. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. Biochem Biophys Res Commun. 2006, 341(4): 1135-1140
25 Mitchell KE, Weiss ML, Mitchell BM, et al. Matrix cells from Wharton′s jelly form neurons and glia. Stem Cells. 2003, 21: 50-60
26 Romanov YA, Svintsitskaya VA, Smirnov V N. Searching for alternative sources of postnatal human mesenchymal stem cells candidate MSC-like cells from umbilical cord. Stem Cells. 2003, 21: 105-110
27 Karahuseyinoglu S, Cinar O, Kilic E, et al. Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys. Stem Cells. 2007, 25: 319-331
28 Chao KC, Chao KF, Fu YS, et al. Islet-like clusters derived from mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord for transplantation to control type 1 diabetes. PLoS One. 2008, 3(1): e1451
29 Lavoie JF, Biernaskie JA, Chen Y, et al. Skin-derived precursors differentiate into skeletogenic cell types and contribute to bone repair. Stem Cells Dev. 2009, 18(6): 893-906
30 Kang Q, Song WX, Luo Q, et al. A comprehensive analysis of the dual roles of BMPs in regulating adipogenic and osteogenic differentiation of mesenchymal progenitor cells. Stem Cells Dev. 2009, 18(4): 545-559
31 Sharp J, Keirstead HS. Stem cell-based cell replacement strategies for the central nervous system. Neurosci Lett. 2009, 456(3): 107-111
32 Aurich H, Sgodda M, Kaltwasser P, et al. Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut. 2009, 58(4): 570-581
33 Fujikawa T, Oh SH, Pi L, et al. Teratoma formation leads to failure of treatment for type I diabetes using embryonic stem cell-derived insulin-producing cells. Am J Pathol. 2005, 166(6): 1781-1791
34 Wang HS, Hung SC, Peng ST, et al. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells. 2004, 22: 1330-1337
35 Sarugaser R, Lickorish D, Baksh D, et al. Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells. 2005, 23: 220-229
36 Fu YS, Cheng YC, Lin MY, et al. Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells. 2006, 24: 115-124
37 Campard D, Lysy PA, Najimi M, et al. Native umbilical cord matrix stem cells express hepatic markers and differentiate into hepatocyte-like cells. Gastroenterology. 2008, 134: 833-848
38 Lu LL, Liu YJ, Yang SG, et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with haematopoiesis-supportive function and other potentials. Haematologica. 2006, 91: 1017-1026
39 Weiss ML, Medicetty S, Bledsoe AR, ET AL. Human umbilical cord matrix stem cell: Preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. STEM CELLS. 2006, 24: 781-792
40李聪然,游雪甫,蒋建东.糖尿病动物模型及研究进展[J].中国比较医学杂志.2005, 15(1): 59-63
41关子安,孙茂欣,关大顺等.现代糖尿病学[M].天津:天津科学技术出版社.2001, 63-68, 56-59
42施新猷,主编.现代医学实验动物学[M].北京:人民军医出版社.2000, 9: 482-484
43许剑,徐格林,刘新峰.骨髓基质干细胞的标记示踪技术及其应用.Chin J Clin Neurosci. 2006, 14(2): 197-201
44 Chang C, Wang X, Niu D, et al. Mesenchymal stem cells adopt beta-cell fate upon diabetic pancreatic microenvironment. Pancreas. 2009, 38(3): 275-281
45 Chang C, Niu D, Zhou H, et al.Mesenchymal stroma cells improve hyperglycemia and insulin deficiency in the diabetic porcine pancreatic microenvironment. Cytotherapy. 2008, 10(8): 796-805
46 Lin G, Wang G, Liu G, et al. Treatment of type 1 diabetes with adipose tissue-derived stem cells expressing pancreatic duodenal homeobox 1. Stem Cells Dev. 2009, 18(10): 1399-1406
47 Vaca P, Martín F, Vegara-Meseguer JM, et al. Induction of differentiation of embryonic stem cells into insulin-secreting cells by fetal soluble factors. Stem Cells. 2006, 24(2): 258-265
48 Fumimoto Y, Matsuyama A, Komoda H, et al.Creation of a rich subcutaneous vascular network with implanted adipose tissue-derived stromal cells and adipose tissue enhances subcutaneous grafting of islets in diabetic mice. Tissue Eng Part C Methods. 2009, 15(3): 437-444
49 Lee J, Wen J, Park JY, et al. Reversal of diabetes in rats using GLP-1-expressing adult pancreatic duct-like precursor cells transformed from acinar to ductal cells. Stem Cells Dev. 2009, 18(7): 991-1002
50 Ende N, Chen R, Reddi AS. Effect of human umbilical cord blood cells on glycemia and insulitis in type 1 diabetic mice. Biochem Biophys Res Commun. 2004, 325(3): 665-669
51 Trivedi HL, Vanikar AV, Thakker U, et al. Human adipose tissue-derived mesenchymal stem cells combined with hematopoietic stem cell transplantation synthesize insulin.Transplant Proc. 2008, 40(4): 1135-1139
52 Li M, Inaba M, Guo KQ, et al. Treatment of streptozotocin-induced diabetes mellitus in mice by intra-bone marrow bone marrow transplantation plus portal vein injection of beta cells induced from bone marrow cells. Int J Hematol. 2007, 86(5): 438-445
53 Xu J, Lu Y, Ding F, et al. Reversal of diabetes in mice by intrahepatic injection of bone-derived GFP-murine mesenchymal stem cells infected with the recombinant retrovirus-carrying human insulin gene. World J Surg. 2007, 31(9): 1872-1882
54 Gabr MM, Sobh MM, Zakaria MM, et al. Transplantation of insulin-producing clusters derived from adult bone marrow stem cells to treat diabetes in rats. Exp Clin Transplant. 2008, 6(3): 236-243
1 Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000, 343: 230-238
2 Mao GH, Chen GA, Bai HY, et al. The reversal of hyperglycaemia in diabetic mice using PLGA scaffolds seeded with islet-like cells derived from human embryonic stem cells. Biomaterials. 2009, 30(9): 1706-1714
3 Chen C, Zhang Y, Sheng X, et al. Differentiation of embryonic stem cells towards pancreatic progenitor cells and their transplantation into streptozotocin-induced diabetic mice. Cell Biol Int. 2008, 32(4): 456-461
4 Shi Y, Hou L, Tang F, et al. Inducing embryonic stem cells to differentiateinto pancreatic beta cells by a novel three-step approach with activin A and all-trans retinoic acid. Stem Cells. 2005, 23(5): 656-662
5 Jiang W, Shi Y, Zhao D, et al. In vitro derivation of functional insulin-producing cells from human embryonic stem cells. Cell Res. 2007, 17(4): 333-344
6 Fujikawa T, Oh SH, Pi L, et al. Teratoma formation leads to failure of treatment for type I diabetes using embryonic stem cell-derived insulin-producing cells. Am J Pathol. 2005, 166(6): 1781-1791
7 Zulewski H, Abraham EJ, Gerlach MJ, et al. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes. 2001, 50(3): 521-533
8 Lee J, Wen J, Park JY, et al. Reversal of diabetes in rats using GLP-1-expressing adult pancreatic duct-like precursor cells transformed from acinar to ductal cells. Stem Cells Dev. 2009, 18(7): 991-1002
9 Huang H, Tang X. Phenotypic determination and characterization of nestin-positive precursors derived from human fetal pancreas. Lab Invest. 2003, 83(4): 539-547
10 Figliuzzi M, Cornolti R, Perico N, et al. Bone marrow-derived mesenchymal stem cells improve islet graft function in diabetic rats. Transplant Proc. 2009, 41(5): 1797-1800
11 Boumaza I, Srinivasan S, Witt WT, et al. Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia. J Autoimmun. 2009, 32(1): 33-42
12 Banerjee M, Kumar A, Bhonde RR. Reversal of experimental diabetes by multiple bone marrow transplantation. Biochem Biophys Res Commun. 2005, 328(1): 318-325
13李立人,徐青.骨髓基质干细胞移植对糖尿病大鼠血糖的影响[J].苏州大学学报(医学版). 2005, 25(4): 584-585
14 Chen LB, Jiang XB, Yang L. Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells. World J Gastroenterol. 2004, 10(20): 3016-3020
15 Zhao M, Amiel SA, Ajami S, et al. Amelioration of streptozotocin-induced diabetes in mice with cells derived from human marrow stromal cells. PLoS One. 2008, 3(7): e2666
16 Li Y, Zhang R, Qiao H, et al. Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells. J Cell Physiol. 2007, 211(1): 36-44
17陆洋,陆玉华,王志伟等.转胰岛素基因的人骨髓间充质干细胞治疗大鼠糖尿病[J].苏州大学学报(医学版).2007, 27(5): 708-711
18 Hu YH, Wu DQ, Gao F, et al. A secretory function of human insulin-producing cells in vivo. Hepatobiliary Pancreat Dis Int. 2009, 8(3): 255-260
19 Chi ZH, Lu Y, Zhang Y. Study on differentiation of mesenchymal stem cells derived from human umbilical cord blood into insulin secreting cells. Zhonghua Xue Ye Xue Za Zhi. 2008, 29(10): 679-683
20 Ende N, Chen R, Reddi AS. Effect of human umbilical cord blood cells on glycemia and insulitis in type 1 diabetic mice. Biochem Biophys Res Commun. 2004, 325(3): 665-669
21 Ende N, Chen R, Reddi AS. Transplantation of human umbilical cord blood cells improves glycemia and glomerular hypertrophy in type 2 diabetic mice. Biochem Biophys Res Commun. 2004, 321(1): 168-171
22 Karahuseyinoglu S, Cinar O, Kilic E, et al. Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys. Stem Cells. 2007, 25: 319-331
23 Campard D, Lysy PA, Najimi M, et al. Native umbilical cord matrix stem cells express hepatic markers and differentiate into hepatocyte-like cells. Gastroenterology. 2008, 134: 833-848
24 Secco M, Zucconi E, Vieira N, et al. Multipotent stem cells from umbilical cord: cord is richer than blood. Stem Cells. 2007, 261: 146-150
25 Wang HS, Hung SC, Peng ST, et al. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells. 2004, 22: 1330-1337
26 Sarugaser R, Lickorish D, Baksh D, et al. Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells. 2005, 23: 220-229
27 Fu YS, Cheng YC, Lin MY, et al. Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells. 2006, 24: 115-124
28 Lu LL, Liu YJ, Yang SG, et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with haematopoiesis-supportive function and other potentials. Haematologica. 2006, 91: 1017-1026
29 Chao KC, Chao KF, Fu YS, et al. Islet-like clusters derived from mesenchymal stem cells in Wharton's Jelly of the human umbilical cord for transplantation to control type 1 diabetes. PLoS One. 2008, 3(1): e1451
30 Kim S, Shin JS, Kim HJ, et al. Streptozotocin-induced diabetes can be reversed by hepatic oval cell activation through hepatic transdifferentiation and pancreatic islet regeneration. Lab Invest. 2007, 87(7): 702-712
31余卫,何冬梅,张洹.胎肝间充质干细胞治疗实验性糖尿病小鼠的研究[J].暨南大学学报(医学版).2007, 28(6): 558-561
32 Yang L, Li S, Hatch H, et al. In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci U S A. 2002, 99(12): 8078-8083
33 Sato A, Okumura K, Matsumoto S, et al. Isolation, tissue localization, and cellular characterization of progenitors derived from adult human salivary glands. Cloning Stem Cells. 2007, 9(2): 191-205
34 Tateishi K, He J, Taranova O, et al. Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem. 2008, 283(46): 31601-31607
35 Chang C, Wang X, Niu D, et al. Mesenchymal stem cells adopt beta-cell fate upon diabetic pancreatic microenvironment. Pancreas. 2009, 38(3): 275-281
36 Fumimoto Y, Matsuyama A, Komoda H, et al. Creation of a rich subcutaneous vascular network with implanted adipose tissue-derived stromal cells and adipose tissue enhances subcutaneous grafting of islets in diabetic mice. Tissue Eng Part C Methods. 2009, 15(3): 437-444
37 Lee J, Wen J, Park JY, et al. Reversal of diabetes in rats using GLP-1-expressing adult pancreatic duct-like precursor cells transformed from acinar to ductal cells. Stem Cells Dev. 2009, 18(7): 991-1002
38 Trivedi HL, Vanikar AV, Thakker U, et al. Human adipose tissue-derived mesenchymal stem cells combined with hematopoietic stem cell transplantation synthesize insulin.Transplant Proc. 2008, 40(4): 1135-1139
39 Li M, Inaba M, Guo KQ, et al. Treatment of streptozotocin-induced diabetes mellitus in mice by intra-bone marrow bone marrow transplantation plus portal vein injection of beta cells induced from bone marrow cells. Int J Hematol. 2007, 86(5): 438-445
40 Xu J, Lu Y, Ding F, et al. Reversal of diabetes in mice by intrahepatic injection of bone-derived GFP-murine mesenchymal stem cells infected with the recombinant retrovirus-carrying human insulin gene. World J Surg. 2007, 31(9): 1872-1882
41 Gabr MM, Sobh MM, Zakaria MM, et al. Transplantation of insulin-producing clusters derived from adult bone marrow stem cells to treat diabetes in rats. Exp Clin Transplant. 2008, 6(3): 236-243
2 Mao GH, Chen GA, Bai HY, et al. The reversal of hyperglycaemia in diabetic mice using PLGA scaffolds seeded with islet-like cells derived from human embryonic stem cell. Biomaterials. 2009, 30(9): 1706-1714
3 Vaca p, Berna G, Araujo R, et al. Nicotinamide induces differentiation of embryonic stem cells into insulin-secreting cells. Exp Cell Res. 2008, 314(5): 969-974
4 Jiang W, Shi Y, Zhao D, et al. In vitro derivation of functional insulin-producing cells from human embryonic stem cells. Cell Res. 2007, 17(4): 333-344
5李艳华,白慈贤,谢超等.成人骨髓间充质干细胞体外定向诱导分化为胰岛样细胞团的研究.自然科学进展.2003, 13(6): 593-597
6 Ai C, Todorov I, Slovak ML, et al. Human marrow-derived mesodermalprogenitor cells generate insulin-secreting islet-like clusters in vivo. Stem Cells Dev. 2007, 16(5): 757-770
7 Wu XH, Liu CP, Xu KF, et al. Reversal of hyperglycemia in diabetic rats by portal vein transplantation of islet-like cells generated from bone marrow mesenchymal stem cells. World J Gastroenterol. 2007, 13(24): 3342-3349
8 Karnieli O, Izhar-Prato Y, Bulvik S, et al. Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation. Stem Cells. 2007, 25(11): 2837-2844
9 Tang DQ, Cao LZ, Burkhardt BR, et al. In Vivo and In Vitro Characterization of Insulin-Producing Cells Obtained From Murine Bone Marrow. Diabetes. 2004, 53: 1721-1732
10 Oh SH, Muzzonigro1 TM, Bae1 SH, et al. Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes. Laboratory Investigation. 2004, 84: 607-617
11 Gao F, Wu DQ, Hu YH, et al.In vitro cultivation of islet-like cell clusters from human umbilical cord blood-derived mesenchymal stem cells. Transl Res. 2008, 151(6): 293-302
12 Sun B, Roh KH, Lee SR, et al. Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure. Biochem Biophys Res Commun. 2007, 354(4): 919-923
13 Choi KS, Shin JS, Lee JJ, et al. In vitro trans-differentiation of rat mesenchymal cells into insulin-producing cells by rat pancreatic extract. Biochem Biophys Res Commun. 2005, 330: 1299-1305
14 Li L, Lili R, Hui Q, et al. Combination of GLP-1 and sodium butyrate promote differentiation of pancreatic progenitor cells into insulin-producing cells. Tissue Cell. 2008, 40(6): 437-445
15 Noguchi H, Xu G, Matsumoto S, et al. Induction of pancreatic stem/progenitor cells into insulin-producing cells by adenoviral-mediated gene transfer technology. Cell Transplant. 2006, 15(10): 929-938
16 Gao R, Ustinov J, PulkkinenMA, et al. Characterization of endocrine progenitor cells and critical factors for their differentiation in human adult pancreatic cell culture. Diabetes. 2003, 52: 2007-2015
17 Li H, Li X, Lam KS, et al. Adeno-associated virus-mediated pancreatic and duodenal homeobox gene-1 expression enhanced differentiation of hepatic oval stem cells to insulin-producing cells in diabetic rats. J Biomed Sci. 2008, 15(4): 487-497
18 Kim S, Shin JS, Kim HJ, et al. Streptozotocin-induced diabetes can be reversed by hepatic oval cell activation through hepatic transdifferentiation and pancreatic islet regeneration. Lab Invest. 2007, 87(7): 702-712
19 Zalzman M, Gupta S, Giri RK, et al. Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells. Proc Natl Acad Sci USA. 2003, 100: 7253-7258
20 Yang L, Li S, Hatch H, et al. In vitro transdifferentiation of adult hepatic stem cells into pancreatic endocrine hormon producing cells. Proc Natl Acad Sci USA. 2002, 99: 8078-8084
21余卫,何冬梅,张洹.胎肝间充质干细胞治疗实验性糖尿病小鼠的研究[J].暨南大学学报(医学版).2007, 28(6): 558-561
22 Tateishi K, He J, Taranova O, et al. Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem. 2008, 283(46): 31601-31607
23 Lee J, Han DJ, Kim SC. In vitro differentiation of human adipose tissue-derived stem cells into cells with pancreatic phenotype by regenerating pancreas extract. Biochem Biophys Res Commun. 2008, 375(4): 547-551
24 Timper K, Seboek D, Eberhardt M, et al. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. Biochem Biophys Res Commun. 2006, 341(4): 1135-1140
25 Mitchell KE, Weiss ML, Mitchell BM, et al. Matrix cells from Wharton′s jelly form neurons and glia. Stem Cells. 2003, 21: 50-60
26 Romanov YA, Svintsitskaya VA, Smirnov V N. Searching for alternative sources of postnatal human mesenchymal stem cells candidate MSC-like cells from umbilical cord. Stem Cells. 2003, 21: 105-110
27 Karahuseyinoglu S, Cinar O, Kilic E, et al. Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys. Stem Cells. 2007, 25: 319-331
28 Chao KC, Chao KF, Fu YS, et al. Islet-like clusters derived from mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord for transplantation to control type 1 diabetes. PLoS One. 2008, 3(1): e1451
29 Lavoie JF, Biernaskie JA, Chen Y, et al. Skin-derived precursors differentiate into skeletogenic cell types and contribute to bone repair. Stem Cells Dev. 2009, 18(6): 893-906
30 Kang Q, Song WX, Luo Q, et al. A comprehensive analysis of the dual roles of BMPs in regulating adipogenic and osteogenic differentiation of mesenchymal progenitor cells. Stem Cells Dev. 2009, 18(4): 545-559
31 Sharp J, Keirstead HS. Stem cell-based cell replacement strategies for the central nervous system. Neurosci Lett. 2009, 456(3): 107-111
32 Aurich H, Sgodda M, Kaltwasser P, et al. Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut. 2009, 58(4): 570-581
33 Fujikawa T, Oh SH, Pi L, et al. Teratoma formation leads to failure of treatment for type I diabetes using embryonic stem cell-derived insulin-producing cells. Am J Pathol. 2005, 166(6): 1781-1791
34 Wang HS, Hung SC, Peng ST, et al. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells. 2004, 22: 1330-1337
35 Sarugaser R, Lickorish D, Baksh D, et al. Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells. 2005, 23: 220-229
36 Fu YS, Cheng YC, Lin MY, et al. Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells. 2006, 24: 115-124
37 Campard D, Lysy PA, Najimi M, et al. Native umbilical cord matrix stem cells express hepatic markers and differentiate into hepatocyte-like cells. Gastroenterology. 2008, 134: 833-848
38 Lu LL, Liu YJ, Yang SG, et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with haematopoiesis-supportive function and other potentials. Haematologica. 2006, 91: 1017-1026
39 Weiss ML, Medicetty S, Bledsoe AR, ET AL. Human umbilical cord matrix stem cell: Preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. STEM CELLS. 2006, 24: 781-792
40李聪然,游雪甫,蒋建东.糖尿病动物模型及研究进展[J].中国比较医学杂志.2005, 15(1): 59-63
41关子安,孙茂欣,关大顺等.现代糖尿病学[M].天津:天津科学技术出版社.2001, 63-68, 56-59
42施新猷,主编.现代医学实验动物学[M].北京:人民军医出版社.2000, 9: 482-484
43许剑,徐格林,刘新峰.骨髓基质干细胞的标记示踪技术及其应用.Chin J Clin Neurosci. 2006, 14(2): 197-201
44 Chang C, Wang X, Niu D, et al. Mesenchymal stem cells adopt beta-cell fate upon diabetic pancreatic microenvironment. Pancreas. 2009, 38(3): 275-281
45 Chang C, Niu D, Zhou H, et al.Mesenchymal stroma cells improve hyperglycemia and insulin deficiency in the diabetic porcine pancreatic microenvironment. Cytotherapy. 2008, 10(8): 796-805
46 Lin G, Wang G, Liu G, et al. Treatment of type 1 diabetes with adipose tissue-derived stem cells expressing pancreatic duodenal homeobox 1. Stem Cells Dev. 2009, 18(10): 1399-1406
47 Vaca P, Martín F, Vegara-Meseguer JM, et al. Induction of differentiation of embryonic stem cells into insulin-secreting cells by fetal soluble factors. Stem Cells. 2006, 24(2): 258-265
48 Fumimoto Y, Matsuyama A, Komoda H, et al.Creation of a rich subcutaneous vascular network with implanted adipose tissue-derived stromal cells and adipose tissue enhances subcutaneous grafting of islets in diabetic mice. Tissue Eng Part C Methods. 2009, 15(3): 437-444
49 Lee J, Wen J, Park JY, et al. Reversal of diabetes in rats using GLP-1-expressing adult pancreatic duct-like precursor cells transformed from acinar to ductal cells. Stem Cells Dev. 2009, 18(7): 991-1002
50 Ende N, Chen R, Reddi AS. Effect of human umbilical cord blood cells on glycemia and insulitis in type 1 diabetic mice. Biochem Biophys Res Commun. 2004, 325(3): 665-669
51 Trivedi HL, Vanikar AV, Thakker U, et al. Human adipose tissue-derived mesenchymal stem cells combined with hematopoietic stem cell transplantation synthesize insulin.Transplant Proc. 2008, 40(4): 1135-1139
52 Li M, Inaba M, Guo KQ, et al. Treatment of streptozotocin-induced diabetes mellitus in mice by intra-bone marrow bone marrow transplantation plus portal vein injection of beta cells induced from bone marrow cells. Int J Hematol. 2007, 86(5): 438-445
53 Xu J, Lu Y, Ding F, et al. Reversal of diabetes in mice by intrahepatic injection of bone-derived GFP-murine mesenchymal stem cells infected with the recombinant retrovirus-carrying human insulin gene. World J Surg. 2007, 31(9): 1872-1882
54 Gabr MM, Sobh MM, Zakaria MM, et al. Transplantation of insulin-producing clusters derived from adult bone marrow stem cells to treat diabetes in rats. Exp Clin Transplant. 2008, 6(3): 236-243
1 Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000, 343: 230-238
2 Mao GH, Chen GA, Bai HY, et al. The reversal of hyperglycaemia in diabetic mice using PLGA scaffolds seeded with islet-like cells derived from human embryonic stem cells. Biomaterials. 2009, 30(9): 1706-1714
3 Chen C, Zhang Y, Sheng X, et al. Differentiation of embryonic stem cells towards pancreatic progenitor cells and their transplantation into streptozotocin-induced diabetic mice. Cell Biol Int. 2008, 32(4): 456-461
4 Shi Y, Hou L, Tang F, et al. Inducing embryonic stem cells to differentiateinto pancreatic beta cells by a novel three-step approach with activin A and all-trans retinoic acid. Stem Cells. 2005, 23(5): 656-662
5 Jiang W, Shi Y, Zhao D, et al. In vitro derivation of functional insulin-producing cells from human embryonic stem cells. Cell Res. 2007, 17(4): 333-344
6 Fujikawa T, Oh SH, Pi L, et al. Teratoma formation leads to failure of treatment for type I diabetes using embryonic stem cell-derived insulin-producing cells. Am J Pathol. 2005, 166(6): 1781-1791
7 Zulewski H, Abraham EJ, Gerlach MJ, et al. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes. 2001, 50(3): 521-533
8 Lee J, Wen J, Park JY, et al. Reversal of diabetes in rats using GLP-1-expressing adult pancreatic duct-like precursor cells transformed from acinar to ductal cells. Stem Cells Dev. 2009, 18(7): 991-1002
9 Huang H, Tang X. Phenotypic determination and characterization of nestin-positive precursors derived from human fetal pancreas. Lab Invest. 2003, 83(4): 539-547
10 Figliuzzi M, Cornolti R, Perico N, et al. Bone marrow-derived mesenchymal stem cells improve islet graft function in diabetic rats. Transplant Proc. 2009, 41(5): 1797-1800
11 Boumaza I, Srinivasan S, Witt WT, et al. Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia. J Autoimmun. 2009, 32(1): 33-42
12 Banerjee M, Kumar A, Bhonde RR. Reversal of experimental diabetes by multiple bone marrow transplantation. Biochem Biophys Res Commun. 2005, 328(1): 318-325
13李立人,徐青.骨髓基质干细胞移植对糖尿病大鼠血糖的影响[J].苏州大学学报(医学版). 2005, 25(4): 584-585
14 Chen LB, Jiang XB, Yang L. Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells. World J Gastroenterol. 2004, 10(20): 3016-3020
15 Zhao M, Amiel SA, Ajami S, et al. Amelioration of streptozotocin-induced diabetes in mice with cells derived from human marrow stromal cells. PLoS One. 2008, 3(7): e2666
16 Li Y, Zhang R, Qiao H, et al. Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells. J Cell Physiol. 2007, 211(1): 36-44
17陆洋,陆玉华,王志伟等.转胰岛素基因的人骨髓间充质干细胞治疗大鼠糖尿病[J].苏州大学学报(医学版).2007, 27(5): 708-711
18 Hu YH, Wu DQ, Gao F, et al. A secretory function of human insulin-producing cells in vivo. Hepatobiliary Pancreat Dis Int. 2009, 8(3): 255-260
19 Chi ZH, Lu Y, Zhang Y. Study on differentiation of mesenchymal stem cells derived from human umbilical cord blood into insulin secreting cells. Zhonghua Xue Ye Xue Za Zhi. 2008, 29(10): 679-683
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