Background Pancreatic islet cell transplantation is an effective approach to treat type 1 diabetes. However, this therapy is not widely used because of the severe shortage of transplantable donor islets. This study in...Background Pancreatic islet cell transplantation is an effective approach to treat type 1 diabetes. However, this therapy is not widely used because of the severe shortage of transplantable donor islets. This study investigated whether mesenchymal stem cells （MSCs） derived from human umbilical cord blood （UCB） could be transdifferentiated into insulin producing cells in vitro and the role of extracellular matrix （ECM） gel in this procedure. Methods Human UCB samples were collected and MSCs were isolated. MSCs specific marker proteins were analyzed by a flow cytometer, The capacities of osteoblast and adipocyte to differentiate were tested. Differentiation into islet like cell was induced by a 15-day protocol with or without ECM gel. Pancreatic characteristics were evaluated with immunofluorescence, reverse transcription polymerase chain reaction （RT-PCR） and flow cytometry. Insulin content and release in response to glucose stimulation were detected with chemiluminescent immunoassay system. Results Sixteen MSCs were isolated from 42 term human UCB units （38%）. Human UCB-MSCs expressed MSCs specific markers and could be induced in vitro into osteoblast and adipocyte. Islet like cell clusters appeared about 9 days after pancreatic differentiation in the inducing system with ECM gel. The insulin positive cells accounted for （25.2~3.4）% of the induced cells. The induced cells expressed islet related genes and hormones, but were not very responsive to glucose challenge. When MSCs were induced without ECM gel, clusters formation and secretion of functional islet proteins could not be observed, Conclusions Human UCB-MSCs can differentiate into islet like cells in vitro and ECM gel plays an important role in pancreatic endocrine cell maturation and formation of three dimensional structures.展开更多
Cell-based regenerative medicine is of growing interest in biomedical research. The role of stem cells in this context is under intense scrutiny and may help to define principles of organ regeneration and develop inno...Cell-based regenerative medicine is of growing interest in biomedical research. The role of stem cells in this context is under intense scrutiny and may help to define principles of organ regeneration and develop innovative therapeutics for organ failure. Utilizing stem and progenitor cells for organ replacement has been conducted for many years when performing hematopoietic stem cell transplantation. Since the first successful transplantation of umbilical cord blood to treat hematological malignancies, non-hematopoietic stem and progenitor cell populations have recently been identified within umbilical cord blood and other perinatal and fetal tissues. A cell population entitled mesenchymal stromal cells (MSCs) emerged as one of the most intensely studied as it subsumes a variety of capacities: MSCs can differentiate into various subtypes of the mesodermal lineage, they secrete a large array of trophic factors suitable of recruiting endogenous repair processes and they are immunomodulatory.Focusing on perinatal tissues to isolate MSCs, we will discuss some of the challenges associated with these cell types concentrating on concepts of isolation and expansion, the comparison with cells derived from other tissue sources, regarding phenotype and differentiation capacity and finally their therapeutic potential.展开更多
文摘目的探讨新生儿脐动脉血气分析与围产期高危因素、Apgar评分和窒息多器官损害的相关性。方法选择2012年11月至2014年12月课题组协作医院新生儿科和新生儿重症监护病房收治的胎龄〉34周、生后检测脐动脉血p H和BE的窒息新生儿,根据Apgar评分诊断新生儿窒息,根据脐血血气分析将轻度窒息组和重度窒息组分别分为严重代谢性酸中毒组（p H≤7和/或BE≤-16mmol/L）、非严重代谢性酸中毒组（77.2且BE〉-8）。根据围产期缺氧病史、临床表现、实验室检查和影像学检查等诊断新生儿窒息多器官损害。结果共纳入新生儿窒息患儿111例,其中轻度窒息79例,重度窒息32例。（1）脐动脉血气p H和BE与1 min Apgar评分成正相关（p H：r=0.223,P=0.016;BE：r=0.293,P=0.002）。（2）多因素分析显示胎心监护异常是影响血气p H和BE的重要因素（β=0.080,95%CI 0.010~0.160,P=0.025）。（3）重度窒息组多器官损害发生率显著高于轻度窒息组（75.0%比29.1%,χ^2=17.810,P〈0.001）。轻度窒息合并严重酸中毒、非严重酸中毒和无酸中毒组多器官损害发生率分别为52.9%、26.3%、16.7%,酸中毒组多器官损害发生率高于无酸中毒组,差异有统计学意义（χ^2=6.623,P=0.036）;重度窒息合并严重酸中毒、非严重酸中毒和无酸中毒组多器官损害发生率分别为80.0%、76.9%、50.0%,均较高,三组比较差异无统计学意义（χ^2=1.559,P=0.459）。（4）患儿1 min Apgar评分0~3分预测窒息多器官损害的敏感度和特异度分别为52.2%和87.1%;脐动脉血p H≤7和BE≤-16的敏感度分别为42.6%和38.3%,特异度分别为87.6和92.2%。（5）Apgar评分、脐动脉血p H和BE多项指标综合用于窒息后多器官损害敏感度和特异度评价,1 min Apgar评分0~3分、5 min Apgar评分≤5分、脐动脉血p H≤7和BE≤-16 mmol/L具有较高的特异度（71.9%）和敏感度（74.5%）。结论脐动脉血p H和BE可准确评价新生�
基金This work was supported by the Natural Science Foundation of Heilongjiang Province （No. ZJY0505）.
文摘Background Pancreatic islet cell transplantation is an effective approach to treat type 1 diabetes. However, this therapy is not widely used because of the severe shortage of transplantable donor islets. This study investigated whether mesenchymal stem cells （MSCs） derived from human umbilical cord blood （UCB） could be transdifferentiated into insulin producing cells in vitro and the role of extracellular matrix （ECM） gel in this procedure. Methods Human UCB samples were collected and MSCs were isolated. MSCs specific marker proteins were analyzed by a flow cytometer, The capacities of osteoblast and adipocyte to differentiate were tested. Differentiation into islet like cell was induced by a 15-day protocol with or without ECM gel. Pancreatic characteristics were evaluated with immunofluorescence, reverse transcription polymerase chain reaction （RT-PCR） and flow cytometry. Insulin content and release in response to glucose stimulation were detected with chemiluminescent immunoassay system. Results Sixteen MSCs were isolated from 42 term human UCB units （38%）. Human UCB-MSCs expressed MSCs specific markers and could be induced in vitro into osteoblast and adipocyte. Islet like cell clusters appeared about 9 days after pancreatic differentiation in the inducing system with ECM gel. The insulin positive cells accounted for （25.2~3.4）% of the induced cells. The induced cells expressed islet related genes and hormones, but were not very responsive to glucose challenge. When MSCs were induced without ECM gel, clusters formation and secretion of functional islet proteins could not be observed, Conclusions Human UCB-MSCs can differentiate into islet like cells in vitro and ECM gel plays an important role in pancreatic endocrine cell maturation and formation of three dimensional structures.
基金Supported by Research Funds of the German Federal Ministry of Education and Research (01GN0531 and 01GN0939)Proj-ect Commissioned by the European Community ("CASCADE"HEALTH-F5-2009-223236).
文摘Cell-based regenerative medicine is of growing interest in biomedical research. The role of stem cells in this context is under intense scrutiny and may help to define principles of organ regeneration and develop innovative therapeutics for organ failure. Utilizing stem and progenitor cells for organ replacement has been conducted for many years when performing hematopoietic stem cell transplantation. Since the first successful transplantation of umbilical cord blood to treat hematological malignancies, non-hematopoietic stem and progenitor cell populations have recently been identified within umbilical cord blood and other perinatal and fetal tissues. A cell population entitled mesenchymal stromal cells (MSCs) emerged as one of the most intensely studied as it subsumes a variety of capacities: MSCs can differentiate into various subtypes of the mesodermal lineage, they secrete a large array of trophic factors suitable of recruiting endogenous repair processes and they are immunomodulatory.Focusing on perinatal tissues to isolate MSCs, we will discuss some of the challenges associated with these cell types concentrating on concepts of isolation and expansion, the comparison with cells derived from other tissue sources, regarding phenotype and differentiation capacity and finally their therapeutic potential.
