生物人工肾小管体外构建的初步研究
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摘要
研究背景
生物人工肾小管辅助装置(bioartificial renal tubule assist device,RAD)是目前治疗终末期肾脏病的有效方法,RAD是肾脏组织工程研究的重点之一,目前国外RAD已经完成由美国食品药品管理局(FAD)批准的Ⅰ/Ⅱ期临床实验,并取得了令人鼓舞的结果.
尽管RAD研究取得了很大的进展,然而,在RAD构建的许多关键问题仍未解决.首先,构建RAD的支架是肾脏组织工程种子细胞生长和增殖的载体,因此如何把支架构建好,是肾脏组织工程研究工作的关键问题之一.其二,中空纤维聚砜膜与种子细胞的更好地黏附,以及其后的生长、增殖、分化等是作好肾脏组织工程研究工作的关键问题之二.
构建RAD的支架的问题:RAD的支架可以用血液透析器,例如F60等,但是如果采用F60,其内的中空纤维的滤过有效面积1.2m~2,假如在1.2m~2的纤维上置入的种子细胞并生长,显然面积过大.在本研究的第一章,针对RAD的支架问题,我们研制了一种生物反应器,以此来克服RAD的支架的缺陷提供了一个有效的办法.
中空纤维聚砜膜与种子细胞的黏附不能满足需要的问题:目前种子细胞种植在生物反应器的中空纤维聚砜膜上,由于聚砜膜表面的疏水性和粗糙度不佳,致使中空纤维聚砜膜与种子细胞的黏附不佳,针对这一缺陷,我们考虑采用如下方法进行改进:对材料表面进行纳米修饰,材料表面特性对细胞的黏附、增殖、分化和凋亡起重要作用.将材料表面进行纳米修饰是材料改性研究的热点之一.
方法
1.研制生物反应器,中空纤维管呈同心圆排列,内植1000根聚砜膜中空纤维,有效表面积0.1m~2,将纳米金组装到中空纤维聚砜膜表面,根据纳米金溶液浸泡纤维的时间分别为0h、2h、5h、14h,共四组,得到4种中空纤维聚砜膜/纳米金仿生支架,观察各组中空纤维聚砜膜的粗糙度、吸水性以及材料的表征等情况。
2.植入非洲恒河绿猴肾细胞细胞株(CV_1细胞)、鼠肾小管上皮细胞株(NRK-52E)等细胞在制备的4种生物反应器内的中空纤维聚砜膜/纳米金仿生支架的中空纤维外腔面,继续培养2周,构建生物人工肾小管,通过采用免疫荧光染色、原子力显微镜和扫描电镜等方法观察中空纤维聚砜膜表面贴壁生长细胞的黏附、铺展、增殖、细胞数目和形貌等变化,以及检测RAD对Na~+、葡萄糖转运功能,观察哇巴因、根皮苷对转运的选择性地抑制作用,并与未植入细胞的空白生物反应器内中空纤维做对照。
3.我们自行改良的扫描电镜观察的方法,对样品制备中乙醇脱水进行了改进,用改良的方法,观察材料表面的成片细胞的图形完整性。
结果
1.我们研制的生物反应器,这种壳体装1000根中空纤维膜,封装的壳体里的中空纤维膜通过试压测试,全通;壳体内的中空纤维膜能做成平板状。
2.我们自行改良的方法,结果图片可见,材料表面成片细胞连接,无断裂,图形完整,从而避免了原来常规方法的图片失真的缺陷。
3.三组纳米化与一组未纳米化的材料相比,三组中空纤维聚砜膜/纳米金的吸水率与未纳米化相比明显增加(P＜0.01),三组纳米化之间比较,5h组的中空纤维聚砜膜/纳米金的吸水率与2h组、14h组相比明显增加(P＜0.05).
4.纳米化与一组未纳米化的材料相比,2h组、5h组中空纤维聚砜膜/纳米金的粗糙度与未纳米化相比明显增加(P＜0.05),三组纳米化之间比较,5h组的中空纤维聚砜膜/纳米金的粗糙度与2h组、14h组相比明显增加(P＞0.05)..
5.三组纳米化与一组未纳米化的材料相比,三组中空纤维聚砜膜/纳米金的的细胞数目与未纳米化相比明显增加(P＜0.01),能显著提高种子细胞贴壁及增殖,三组纳米化之间比较,5h组的中空纤维聚砜膜/纳米金的粗糙度与14h组相比明显增加(P＜0.05).。
6.培育14天后的RAD组具有对Na~+和葡萄糖的转运功能,转运率在哇巴因、根皮苷作用后明显降低;去除药物抑制因素后,Na~+、葡萄糖转运率又能恢复,与对照组比较差异有显著性意义(P＜0.01)。
结论
1.成功地研制生物反应器,并用于构建RAD的支架。
2.我们研制了一种扫描电镜的样本制备的新方法,这种方法适合观察中空纤维聚砜/纳米金表面生长的细胞,能真实的观察到成片生长细胞的形貌,避免了原来的常规方法对样品的形态的破坏.
3.我们研制了中空纤维聚砜膜/纳米金仿生支架,全部三组纳米化与一组未纳米化的材料相比能显著提高种子细胞贴壁及增殖,其中5小时组的中空纤维聚砜膜/纳米金的生物学性能最佳,中空纤维聚砜膜/纳米金的表面修饰方法对于中空纤维聚砜膜表面改性有着重要意义。
4.初步成功建立了一种体外构建生物人工肾小管的新方法.我们体外构建了生物人工肾小管,其具备RAD的Na~+、葡萄糖选择性转运功能,本研究为RAD的临床应用提供了一定的实验证据。
Background
Bioartificial renal tubule assist device(RAD) is an efficient therapy for end-stage renal disease.With the progress in study on engineering kidney,there are several problems to be solved,such as how to obtain a bioartificial kidney and how to make seeding cells growing on the surface of the scaffold?
Materials and methods
1.The nano-sized gold colloid was prepared by chemical reduction.Polysulfone hollow fiber membrane/nano-sized gold colloid scaffold was fabricated by self-assembly technology.Africa green monkey kidney cell line CV_1 cells were cultured on the surface of the scaffold.Inoculation time of the membrane and nano-sized gold colloid was 0h,2h,5h and 14h respectively.Cell attachment and proliferation were examined with scanning electron microscopy.
2.The construction of RAD.Rat kidney proximal renal tubule cell line NRK-52E cells were seeded onto the outer space of the bioreactor hollow fiber cartridges and incubated for two weeks.And then,the transport rates of sodium and glucose were measured.Meanwhile,the inhibitory effects of oubaine and phlorizin on the transport of sodium and glucose were determined and compared with control device.
Results
1.Biological features of the polysulfone hollow fiber membrane/nano-sized gold colloid scaffold:Surface roughness(Ra values) of four kinds of scaffolds(0 h,2h,5h, 14h) were 29.43±12.38nm,53.02±23.52 nm,61.57±16.08 nm and 51.42±12.22 nm respectively.Water absorption ratios of them were 40.71±2.26%,61.96±3.85%, 70.26±4.24%and 63.21±4.67%respectively,and the highest ratio was seen at 5 hours.
2.Growth of seeding cells on the outer surface of the polysulfone hollow fiber membranes of RAD:Cell attachment and proliferation on the 2h,5h 14h scaffolds were better than that of the Oh scaffold(P＜0.05),and the highest cell number was also seen at 5 hours.In the scaffolds(2h,5h,and 14h) groups,growth of seeded cells with many microvillus was seen on the hollow fibre surface but not the hollow fibre in control group.
Transport functions of the RAD:After 14 days of incubation,cells on the RAD had functions of transporting sodium and glucose,which could be inhibited significantly by oubaine and phlorizin,and could be recovered after agents were removed.
Conclusions
A bioartificial renal tubule assist device was successfully made with the polysulfone hollow fiber membrane/nano-sized gold colloid scaffold.It had increased water absorption,cell adhesion and proliferation,and had the function of transporting sodium and glucose.
生物人工肾小管辅助装置(bioartificial renal tubule assist device,RAD)是目前治疗终末期肾脏病的有效方法,RAD是肾脏组织工程研究的重点之一,目前国外RAD已经完成由美国食品药品管理局(FAD)批准的Ⅰ/Ⅱ期临床实验,并取得了令人鼓舞的结果.
尽管RAD研究取得了很大的进展,然而,在RAD构建的许多关键问题仍未解决.首先,构建RAD的支架是肾脏组织工程种子细胞生长和增殖的载体,因此如何把支架构建好,是肾脏组织工程研究工作的关键问题之一.其二,中空纤维聚砜膜与种子细胞的更好地黏附,以及其后的生长、增殖、分化等是作好肾脏组织工程研究工作的关键问题之二.
构建RAD的支架的问题:RAD的支架可以用血液透析器,例如F60等,但是如果采用F60,其内的中空纤维的滤过有效面积1.2m~2,假如在1.2m~2的纤维上置入的种子细胞并生长,显然面积过大.在本研究的第一章,针对RAD的支架问题,我们研制了一种生物反应器,以此来克服RAD的支架的缺陷提供了一个有效的办法.
中空纤维聚砜膜与种子细胞的黏附不能满足需要的问题:目前种子细胞种植在生物反应器的中空纤维聚砜膜上,由于聚砜膜表面的疏水性和粗糙度不佳,致使中空纤维聚砜膜与种子细胞的黏附不佳,针对这一缺陷,我们考虑采用如下方法进行改进:对材料表面进行纳米修饰,材料表面特性对细胞的黏附、增殖、分化和凋亡起重要作用.将材料表面进行纳米修饰是材料改性研究的热点之一.
方法
1.研制生物反应器,中空纤维管呈同心圆排列,内植1000根聚砜膜中空纤维,有效表面积0.1m~2,将纳米金组装到中空纤维聚砜膜表面,根据纳米金溶液浸泡纤维的时间分别为0h、2h、5h、14h,共四组,得到4种中空纤维聚砜膜/纳米金仿生支架,观察各组中空纤维聚砜膜的粗糙度、吸水性以及材料的表征等情况。
2.植入非洲恒河绿猴肾细胞细胞株(CV_1细胞)、鼠肾小管上皮细胞株(NRK-52E)等细胞在制备的4种生物反应器内的中空纤维聚砜膜/纳米金仿生支架的中空纤维外腔面,继续培养2周,构建生物人工肾小管,通过采用免疫荧光染色、原子力显微镜和扫描电镜等方法观察中空纤维聚砜膜表面贴壁生长细胞的黏附、铺展、增殖、细胞数目和形貌等变化,以及检测RAD对Na~+、葡萄糖转运功能,观察哇巴因、根皮苷对转运的选择性地抑制作用,并与未植入细胞的空白生物反应器内中空纤维做对照。
3.我们自行改良的扫描电镜观察的方法,对样品制备中乙醇脱水进行了改进,用改良的方法,观察材料表面的成片细胞的图形完整性。
结果
1.我们研制的生物反应器,这种壳体装1000根中空纤维膜,封装的壳体里的中空纤维膜通过试压测试,全通;壳体内的中空纤维膜能做成平板状。
2.我们自行改良的方法,结果图片可见,材料表面成片细胞连接,无断裂,图形完整,从而避免了原来常规方法的图片失真的缺陷。
3.三组纳米化与一组未纳米化的材料相比,三组中空纤维聚砜膜/纳米金的吸水率与未纳米化相比明显增加(P＜0.01),三组纳米化之间比较,5h组的中空纤维聚砜膜/纳米金的吸水率与2h组、14h组相比明显增加(P＜0.05).
4.纳米化与一组未纳米化的材料相比,2h组、5h组中空纤维聚砜膜/纳米金的粗糙度与未纳米化相比明显增加(P＜0.05),三组纳米化之间比较,5h组的中空纤维聚砜膜/纳米金的粗糙度与2h组、14h组相比明显增加(P＞0.05)..
5.三组纳米化与一组未纳米化的材料相比,三组中空纤维聚砜膜/纳米金的的细胞数目与未纳米化相比明显增加(P＜0.01),能显著提高种子细胞贴壁及增殖,三组纳米化之间比较,5h组的中空纤维聚砜膜/纳米金的粗糙度与14h组相比明显增加(P＜0.05).。
6.培育14天后的RAD组具有对Na~+和葡萄糖的转运功能,转运率在哇巴因、根皮苷作用后明显降低;去除药物抑制因素后,Na~+、葡萄糖转运率又能恢复,与对照组比较差异有显著性意义(P＜0.01)。
结论
1.成功地研制生物反应器,并用于构建RAD的支架。
2.我们研制了一种扫描电镜的样本制备的新方法,这种方法适合观察中空纤维聚砜/纳米金表面生长的细胞,能真实的观察到成片生长细胞的形貌,避免了原来的常规方法对样品的形态的破坏.
3.我们研制了中空纤维聚砜膜/纳米金仿生支架,全部三组纳米化与一组未纳米化的材料相比能显著提高种子细胞贴壁及增殖,其中5小时组的中空纤维聚砜膜/纳米金的生物学性能最佳,中空纤维聚砜膜/纳米金的表面修饰方法对于中空纤维聚砜膜表面改性有着重要意义。
4.初步成功建立了一种体外构建生物人工肾小管的新方法.我们体外构建了生物人工肾小管,其具备RAD的Na~+、葡萄糖选择性转运功能,本研究为RAD的临床应用提供了一定的实验证据。
Background
Bioartificial renal tubule assist device(RAD) is an efficient therapy for end-stage renal disease.With the progress in study on engineering kidney,there are several problems to be solved,such as how to obtain a bioartificial kidney and how to make seeding cells growing on the surface of the scaffold?
Materials and methods
1.The nano-sized gold colloid was prepared by chemical reduction.Polysulfone hollow fiber membrane/nano-sized gold colloid scaffold was fabricated by self-assembly technology.Africa green monkey kidney cell line CV_1 cells were cultured on the surface of the scaffold.Inoculation time of the membrane and nano-sized gold colloid was 0h,2h,5h and 14h respectively.Cell attachment and proliferation were examined with scanning electron microscopy.
2.The construction of RAD.Rat kidney proximal renal tubule cell line NRK-52E cells were seeded onto the outer space of the bioreactor hollow fiber cartridges and incubated for two weeks.And then,the transport rates of sodium and glucose were measured.Meanwhile,the inhibitory effects of oubaine and phlorizin on the transport of sodium and glucose were determined and compared with control device.
Results
1.Biological features of the polysulfone hollow fiber membrane/nano-sized gold colloid scaffold:Surface roughness(Ra values) of four kinds of scaffolds(0 h,2h,5h, 14h) were 29.43±12.38nm,53.02±23.52 nm,61.57±16.08 nm and 51.42±12.22 nm respectively.Water absorption ratios of them were 40.71±2.26%,61.96±3.85%, 70.26±4.24%and 63.21±4.67%respectively,and the highest ratio was seen at 5 hours.
2.Growth of seeding cells on the outer surface of the polysulfone hollow fiber membranes of RAD:Cell attachment and proliferation on the 2h,5h 14h scaffolds were better than that of the Oh scaffold(P＜0.05),and the highest cell number was also seen at 5 hours.In the scaffolds(2h,5h,and 14h) groups,growth of seeded cells with many microvillus was seen on the hollow fibre surface but not the hollow fibre in control group.
Transport functions of the RAD:After 14 days of incubation,cells on the RAD had functions of transporting sodium and glucose,which could be inhibited significantly by oubaine and phlorizin,and could be recovered after agents were removed.
Conclusions
A bioartificial renal tubule assist device was successfully made with the polysulfone hollow fiber membrane/nano-sized gold colloid scaffold.It had increased water absorption,cell adhesion and proliferation,and had the function of transporting sodium and glucose.
引文
1 Humes HD.The bioartificial tubule assist device:prospects to improve supportive care in acute renal failure.Ren Fail,1996,18(3):405-408
2 Klenzak J,Himmelfarb J.Sepsis and the kidney.Crit Care Clin,2005,21(2):211-222
3 Fissell WH,Dyke DB,Weitzel WF,et al.Bioartificial kidney alters cytokine response and hemodynamics in endotoxin-challenged uremic animals.Blood Purif,2002,20:55-60
4 Humes HD.Stem cells:The next therapeutic frontier.Trans Am Clin Climatol Assoc,2005,116:167-183;discussion 183-184
5 Fissell WH,Lou L,Abrishami S.Bioartificial kidney ameliorates gram-negative bacteria induced septic shock in uremic animals.J Am Soc Nephrol,2003,14:454-461
6 Humes HD,Weitzel WF,Fissell WH,et al.Renal cell therapy in the treatment of patients with acute and chronic renal failure.Blood Purif,2004,22:60-72
7 Tiranathanagul K,Eiam OS,Humes HD,et al.The future of renal support high-flux dialysis to bioartificial kidneys.Crit Care Clin,2005,21:379-394
8 Humes HD,Szczpkq MS.Advances in cell therapy for renal failure.Transpl Immunol.2004,12:219-227
9 Humes HD,Weitzel WF,Bartlett RH,et al.Initial clinical results of the bioartificial kidney containing human cells in ICU patients with acute renal failure.Kidney Int.,2004,66:1578-1588
10 Szczpkq MS,Westover AJ,Clouthier SG,et al.Rare incorporation of bone marrow cells into kidney after folic acid-induced injury.Stem Cells,2005,23:44-54
11 Brodie Jc,Humes HD.Stem cell approaches for the treatment of renal failure.Pharmacol Rev,2005,57:299-313
12 Humes HD,Weitzel WF,Bartlett RH,et al.Renal cell therapy is associated with dynamic and individualized responses in patients with acute renal failure.Blood Purif,2003,21:64-71
13 Humes HD,Fissell WH.The future of hemodialysis membranes.Kidney Int.,2006,69:1115-1119
14 Fissell WH,Manley S,Westover AJ,,et al.Differentiated growth of human renal tubule cells on thin film and nanostructured materials.ASAIO J,2006,52:221-227
15 Gong X,Lu Y,Yu J,et al.Polysulphone microcapsules containing silicone oil for the removal of toxic volatile organics from water.J Micoencapsulation 2008;25(3):196-202
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17 Inagaki M,Yokoyama TA,Sawada K,et al.Prevention of LLC-PK_1 cell overgrowth in a Bioartificial renal tubule assist device using a MEK inhibitor,U0126.J BioTechnology,2007;132(1):57-64
18 Nechemia Arbely Y,Barkan D,Pizov G,et al.IL-6/IL-6R axis plays a critical role in acute kidney injury,J AM Soc Nephrol.2008;19(6):1106-1115
19 Webster TJ,Ergun C,Doremus RH,et al.Specific protein mediate enhanced obteoblast adhesion on nanophase ceramics J Biomed Mater Res,2000,51(3):475-483
20 Li J,Yu J,Zhao F,et al.Direct electrochemistry of glucose oxidese entrapped in nano-sized gold particles-ionic liquid-N N-dimethylformamide composite folm on glassy carbon electrode and glucose sensing.Anal Chim Acta,2007,587(1):33-40
21 Jena BK,Raj CR.Optical sensing of biomedically important polyionic drugs using nano-sized gold particles.Biosens Bioelectron,2008,23(8):1285-1290
22 im HK,Jang JW,Lee CH.Surface modification of implant materials and its effect on attachment and proliferation of bone cell.J Mater Sci Mater Med,2004,15:825-830
23 李清刚.生物人工肾的研究进展.生物医学工程与临床杂志,2001,5(1):39-42
24 Ikuchi A,Okano T.Nanostructured designs of biomedical materials:applications of cell sheet engineering to functional regenerative tissues and organs.J Control Releas,2005;101(1-3):69-84
1 Humes HD.The bioartificial tubule assist device:prospects to improve supportive care in acute renal failure.Ren Fail,1996,18(3):405-408
2 Klenzak J,Himmelfarb J.Sepsis and the kidney.Crit Care Clin,2005,21(2):211-222
3 Webster TJ,Ergun C,Doremus RH,et al.Specific protein mediate enhanced obteoblast adhesion on nanophase ceramics.J Biomed Mater Res,2000,51(3):475-483
4 Li J,Yu J,Zhao F,et al.Direct electrochemistry of glucose oxidese entrapped in nano-sized gold particles-ionic liquid-N N-dimethylformamide composite folm on glassy carbon electrode and glucose sensing.Anal Chim Acta,2007,587(1):33-40
5 Jena BK,Raj CR.Optical sensing of biomedically important polyionic drugs using nano-sized gold particles.Biosens Bioelectron,2008,23(8):1285-1290
6 Kim HK,Jang JW,Lee CH.Surface modification of implant materials and its effect on attachment and proliferation of bone cell.J Mater Sci Mater Med,2004,15:825-830
7 李清刚.生物人工肾的研究进展.生物医学工程与临床杂志,2001,5(1):39-42
8 Kikuchi A,Okano T.Nanostructured designs of biomedical materials:applications of cell sheet engineering to functional regenerative tissues and organs.J Control Releas.2005;101(1-3):69-84
9 Hallab J,Bundy KJ,Oconnor K,et al.Cell adhesion to biomaterials:correlations between surface change,surface roughness,absorbed protein,and cell morphology.J Long Term Eff Med Implants.1995,5(3):209-231
10 Ludwig T,Kirmse R,Poole K,et al.Probing cellular microenvironments and tissue remodeling by atomic force microscopy.Pflugers Arch.2008;456(1):29-49
11 Hirano Y,Takahashi H,Kumeta M,et al.Nuclear architecture and chromatin dynamics revealed by atomic force microscopy in combination with biochemistry and cell biology.Pflugers Arch.2008;456(1):139-153
12 Hillebrand U,Hausberg M,Lang D,et al.How sreroid hormones act on the endothelium isights by atomic force microscopy.Pflugers Arch.2008;456(1):51-60
13 Valois CR,Silva LP,Azevedo RB.Multiple autoclave cycles affect the surface of rotary nickel-titanium files:an atomic force microscopy study.J Endod,2008;34(7):859-862
14 Vadillo RV,Beveridge TJ,Dutcher JR.Surface viscoelasticity of individual gram-negative bacterial cells measured using atomic force microscopy.J Bacteriol,2008;190(12):4225-5232
15 Tiranathanagul K,Eiam OS,Humes HD,et al.The future of renal support high-flux dialysis to bioartificial kidneys.Crit Care Clin,2005,21:379-394
16 Humes HD,Szczpkq MS.Advances in cell therapy for renal failure.Transpl Immunol.2004,12:219-227
17 Humes HD,Fissell WH.The future of hemodialysis membranes.Kidney Int.,2006,69:1115-1119
18 Klenzak J,Himmelfarb J.Sepsis and the kidney.Crit Care Clin,2005,21(2):211-222
19 Fissell WH,Lou L,Abrishami S.Bioartificial kidney ameliorates gram-negative bacteria induced septic shock in uremic animals.J Am Soc Nephrol,2003,14:454-461
20 Fissell WH,Manley S,Westover AJ,et al.Differentiated growth of human renal tubule cells on thin film and nanostructured materials.ASAIO J,2006,52:221-227
21 Gu HY,Chen Z,Sa RX,et al.The immobilization of hepatocytes on 24nm-sized gold colloid for enhanced hepatocytes proliferation.Biomaterials.2004;25(17):3445.3451
22 Gong X,Lu Y,Yu J,et al.Polysulphone microcapsules containing silicone oil for the removal of toxic volatile organics from water,J Micoencapsulation 2008;25(3):196-202
23 Jena BK,Raj CR.Optical sensing of biomedically important polyionic drugs using nano-sized gold particles.Biosens Bioelectron,2008,23(8):1285-1290
24 Zhang W,Li G..Third-generation biosensors based on the direct electron transfer of protein.Anal Sci.2004;20(4):603-609
25 Liu YJ,Nie LH,Tao WY,et al.Amperometric study of Au-colloid function on xanthine biosensors based on xanthine oxidase immobililized in polypyrrole layer.Electroanalysis.2004;16(15):1271-1278
26 王中林编.纳米材料表征.北京:化学工业出版社,2005:245-256
27 倪星元,沈军,张志华.纳米材料的理化特性与应用.北京:化学工业出版社,2005:32-35
28 徐国财,张立德.纳米复合材料.北京:化学工业出版社,2002:9-18
1 Li J,Yu J,Zhao F,et al.Direct electrochemistry of glucose oxidese entrapped in nano-sized gold particles-ionic liquid-N N-dimethylformamide composite folm on glassy carbon electrode and glucose sensing.Anal Chim Acta,2007,587(1):33-40
2 Jena BK,Raj CR.Optical sensing of biomedically important polyionic drugs using nano-sized gold particles.Biosens Bioelectron,2008,23(8):1285-1290
3 Kim HK,Jang JW,Lee CH.Surface modification of implant materials and its effect on attachment and proliferation of bone cell.J Mater Sci Mater Med,2004,15:825-830
4 李清刚.生物人工肾的研究进展.生物医学工程与临床杂志,2001,5(1):39-42
5 徐国财,张立德.纳米复合材料.北京:化学工业出版社,2002:9-18
6 Kikuchi A,Okano T.Nanostructured designs of biomedical materials:applications of cell sheet engineering to functional regenerative tissues and organs.J Control Releas.2005;101(1-3 ):69-84
7 Hallab NJ,Bundy KJ,Oconnor K,et al.Cell adhesion to biomaterials:correlations between surface change,surface roughness,absorbed protein,and cell morphology.J Long Term Eff Med Implants.1995,5(3):209-231
8 Webster TJ,Ergun C,Doremus RH,et al.Specific protein mediate enhanced obteoblast adhesion on nanophase ceramics.J Biomed Mater Res,2000,51(3):475-483
9 Giancotti FG,Ruoaslahti E,Elevated levels of the alpha 5 betal fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cell.Cell,1990,60(5):849-859
10 Amirpour ML,Ghosh P,Lackowski WM,et al.Mammalian cell cultures on micropatterned surfaces of weak-acid,polyeletrolyte hyperbranched thin films on gold.Anal Chem 2001,73(7):1560-1566
11 Noh HK,Lee SW,Kim JM,et al.Electrospinning of chitin nanofibers:degradation behavior and cellular response to normal human keratinocytes and fibroblasts.Biomaterials,2006;27(2):3934-3944
12 Zhang W,Li G Third-generation biosensors based on the direct electron transfer of protein.Anal Sci.2004;20(4):603-609
13 Manisha S,Emestro B,Franciea Y,et al.Taxol inhibits endosomal-lysosomal membrane trafficking at two distinct in CV-1 cells.Am J Physiol Cell Physiol,1998,275:1630-1639
14 Katia RK,Multiresolution algorithms for massively parallel molecular dynamics simulations of nanostructured materials.Computer Physics Communication,2000(128):245-247
15 Dunn GA,Brown AF.Alignment of fibroblasts on grooved surfaces described bysimple geometric transformation.J Cell Sci,1986(83):313-340
16 Clark P.Cell behavior on micropatterned surfaces.Biosens.Bioelectron,1994,9:657-661
17 Fissell WH,Manley S,Westover AJ,et al.Differentiated growth of human renal tubule cells on thin film and nanostructured materials.ASAIO J,2006,52:221-227
18 Li J,Yu J,Zhao F,et al.Direct electrochemistry of glucose oxidese entrapped in nano-sized gold particles-ionic liquid-N N-dimethylformamide composite folm on glassy carbon electrode and glucose sensing.Anal Chim Acta,2007,587(1):33-40
1 Wang H,Ma S.The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome.Am J Emerg Med,2008;26(6):711-715
2 Fissell WH,Humes HD,Fleischman AJ,et al.Dialysis and nanotechnology:now,10 years,or never? Blood Purif,2007;25:12-17
3 Humes HD,Mackay SM,FunkeAJ,et al.The bioartifiacial renal tubule assist device to enhance CRRT in acute renal failure.Ren Fail,1996,18:405-408
4 Humes HD,Mackay SM,Funke AJ,et al.Tissue engineering of a bioartificial renal tubule assist device:In vitro transport and metabolic characteristics.Kidney Int,1999,55:2502-2514
5 Yiranathanagul K,Dhawan V,Lytle IF,et al.Tissue engineering of an implantable bioartificial hemofilter.ASAIO J,2007;53:176-186
6 Tumlin J,Wali R,Williams W,et al.Efficacy and safety of renal tubule cell therapy for acute renal failure.J Am Soc Nephrol,2008;19:1034-1040
7 Issa N,Messer J,Paganini EP.Renal assist device and treatment of sepsis-induced acute kidney injury in intensive care units.Contrib Nephrol,2007;156:419-427
8 董兴刚,陈江华,何强.生物人工肾小管10年回顾与展望。国际移植和血液净化杂志,2008,6:41-42
9 董兴刚,陈江华,何强,等.血滤器的中空纤维聚砜膜的形态学观察方法的探讨和评价.科技通报,2008,24:636-640
10 Li L,Pan J,YU Y.Development of sorbent therapy for multiple organ dysfunction syndrome.Biomed Mater.2007;2(2):R12-16
11 Fissell WH,Fleischman AJ,Humes HD,et al.Development of continuous implantable renal replacement:past and future.Transl Res,2007,150:327-336
12 Humes HD.Fissell WH.Tiranathanagul K.The future of hemodialvsis membranes.Kidney Int.2006,69:1115-1119
13 Tiranathanagul K,Eiam OS,Humes HD,et al.The future of renal support high-flux dialysis to bioartificial kidneys.Crit Care Clin,2005,21:379-394
14 Fissell WH,Manley S,Westover AJ,,et al.Differentiated growth of human renal tubule cells on thin film and nanostructured materials.ASAIO J,2006,52:221-227
15 应旭昱,王笑云,沈霞.生物人工肾小管体外构建及对氨基酸、钠离子、肌酐转运功能的研究.中华肾脏病杂志,2004,20(4):118-121
16 Fissell WH,Lou L,Abrishami S.Bioartificial kidney ameliorates gram-negative bacteria induced septic shock in uremic animals.J Am Soc Nephrol,2003,14:454-461
17 Humes HD,Weitzel WF,Bartlett RH,et al.Initial clinical results of the bioartificial kidney containing human cells in ICU patients with acute renal failure.Kidney Int.,2004,66:1578-1588
18 Humes HD,Weitzel WF,Fissell WH,et al.Renal cell therapy in the treatment of patients with acute and chronic renal failure.Blood Purif,2004,22:60-72
1.Humes HD.Ren Fail,1996,18:405-408
2.Klenzak J,Himmelfarb J.Crit Care Clin,2005,21:211-222
3.Fissell WH,Dyke DB,Weitzel WF,et al.Blood Purif,2002,20:55-60
4.Humes HD.Trans Am Clin Climatol Assoc,2005,116:167-183;discussion 183-184
5.Fissell WH,Lou L,Abrishami S.J Am Soc Nephrol,2003,14:454-461
6.Humes HD,Weitzel WF,Fissell WH,et al.Blood Purif,2004,22:60-72
7.Tiranathanagul K,Eiam OS,Humes HD,et al.Crit Care Clin,2005,21:379-394
8.Humes HD,Szczpkq MS.Transpl Immunol.2004,12:219-227
9.Humes HD,Weitzel WF,Bartlett RH,et al.Kidney Int.,2004,66:1578-1588
10.Szczpkq MS,Westover AJ,Clouthier SG,et al.Stem Cells,2005,23:44-54
11.Brodie Jc,Humes HD.Pharmacol Rev,2005,57:299-313
12.Humes HD,Weitzel WF,Bartlett RH,et al.Blood Purif,2003,21:64-71
13.Humes HD,Fissell WH.Kidney Int.,2006,69:1115-1119
14.Fissell WH,Manley S,Westover AJ,,et al.ASAIO J,2006,52:221-227
1 Humes HD.The bioartificial tubule assist device:prospects to improve supportive care in acute renal failure.Ren Fail,1996,18(3):405-408
2 Klenzak J,Himmelfarb J.Sepsis and the kidney.Crit Care Clin,2005,21(2):211-222
3 Fissell WH,Dyke DB,Weitzel WF,et al.Bioartificial kidney alters cytokine response and hemodynamics in endotoxin-challenged uremic animals.Blood Purif,2002,20:55-60
4 Humes HD.Stem cells:The next therapeutic frontier.Trans Am Clin Climatol Assoc,2005,116:167-183;discussion 183-184
5 Fissell WH,Lou L,Abrishami S.Bioartificial kidney ameliorates gram-negative bacteria induced septic shock in uremic animals.J Am Soc Nephrol,2003,14:454-461
6 Humes HD,Weitzel WF,Fissell WH,et al.Renal cell therapy in the treatment of patients with acute and chronic renal failure.Blood Purif,2004,22:60-72
7 Tiranathanagul K,Eiam OS,Humes HD,et al.The future of renal support high-flux dialysis to bioartificial kidneys.Crit Care Clin,2005,21:379-394
8 Humes HD,Szczpkq MS.Advances in cell therapy for renal failure.Transpl Immunol.2004,12:219-227
9 Humes HD,Weitzel WF,Bartlett RH,et al.Initial clinical results of the bioartificial kidney containing human cells in ICU patients with acute renal failure.Kidney Int.,2004,66:1578-1588
10 Szczpkq MS,Westover AJ,Clouthier SG,et al.Rare incorporation of bone marrow cells into kidney after folic acid-induced injury.Stem Cells,2005,23:44-54
11 Brodie Jc,Humes HD.Stem cell approaches for the treatment of renal failure.Pharmacol Rev,2005,57:299-313
12 Humes HD,Weitzel WF,Bartlett RH,et al.Renal cell therapy is associated with dynamic and individualized responses in patients with acute renal failure.Blood Purif,2003,21:64-71
13 Humes HD,Fissell WH.The future of hemodialysis membranes.Kidney Int.,2006,69:1115-1119
14 Fissell WH,Manley S,Westover AJ,,et al.Differentiated growth of human renal tubule cells on thin film and nanostructured materials.ASAIO J,2006,52:221-227
2 Klenzak J,Himmelfarb J.Sepsis and the kidney.Crit Care Clin,2005,21(2):211-222
3 Fissell WH,Dyke DB,Weitzel WF,et al.Bioartificial kidney alters cytokine response and hemodynamics in endotoxin-challenged uremic animals.Blood Purif,2002,20:55-60
4 Humes HD.Stem cells:The next therapeutic frontier.Trans Am Clin Climatol Assoc,2005,116:167-183;discussion 183-184
5 Fissell WH,Lou L,Abrishami S.Bioartificial kidney ameliorates gram-negative bacteria induced septic shock in uremic animals.J Am Soc Nephrol,2003,14:454-461
6 Humes HD,Weitzel WF,Fissell WH,et al.Renal cell therapy in the treatment of patients with acute and chronic renal failure.Blood Purif,2004,22:60-72
7 Tiranathanagul K,Eiam OS,Humes HD,et al.The future of renal support high-flux dialysis to bioartificial kidneys.Crit Care Clin,2005,21:379-394
8 Humes HD,Szczpkq MS.Advances in cell therapy for renal failure.Transpl Immunol.2004,12:219-227
9 Humes HD,Weitzel WF,Bartlett RH,et al.Initial clinical results of the bioartificial kidney containing human cells in ICU patients with acute renal failure.Kidney Int.,2004,66:1578-1588
10 Szczpkq MS,Westover AJ,Clouthier SG,et al.Rare incorporation of bone marrow cells into kidney after folic acid-induced injury.Stem Cells,2005,23:44-54
11 Brodie Jc,Humes HD.Stem cell approaches for the treatment of renal failure.Pharmacol Rev,2005,57:299-313
12 Humes HD,Weitzel WF,Bartlett RH,et al.Renal cell therapy is associated with dynamic and individualized responses in patients with acute renal failure.Blood Purif,2003,21:64-71
13 Humes HD,Fissell WH.The future of hemodialysis membranes.Kidney Int.,2006,69:1115-1119
14 Fissell WH,Manley S,Westover AJ,,et al.Differentiated growth of human renal tubule cells on thin film and nanostructured materials.ASAIO J,2006,52:221-227
15 Gong X,Lu Y,Yu J,et al.Polysulphone microcapsules containing silicone oil for the removal of toxic volatile organics from water.J Micoencapsulation 2008;25(3):196-202
16 Sombolos KI,Fragia TK,Gionanlis LC,et al.Use of fondaparinux as an anticoagulant during hamodialysis.A Preliminary study.Int J Clin Pharmacol Ther.2008;46(4),198-203
17 Inagaki M,Yokoyama TA,Sawada K,et al.Prevention of LLC-PK_1 cell overgrowth in a Bioartificial renal tubule assist device using a MEK inhibitor,U0126.J BioTechnology,2007;132(1):57-64
18 Nechemia Arbely Y,Barkan D,Pizov G,et al.IL-6/IL-6R axis plays a critical role in acute kidney injury,J AM Soc Nephrol.2008;19(6):1106-1115
19 Webster TJ,Ergun C,Doremus RH,et al.Specific protein mediate enhanced obteoblast adhesion on nanophase ceramics J Biomed Mater Res,2000,51(3):475-483
20 Li J,Yu J,Zhao F,et al.Direct electrochemistry of glucose oxidese entrapped in nano-sized gold particles-ionic liquid-N N-dimethylformamide composite folm on glassy carbon electrode and glucose sensing.Anal Chim Acta,2007,587(1):33-40
21 Jena BK,Raj CR.Optical sensing of biomedically important polyionic drugs using nano-sized gold particles.Biosens Bioelectron,2008,23(8):1285-1290
22 im HK,Jang JW,Lee CH.Surface modification of implant materials and its effect on attachment and proliferation of bone cell.J Mater Sci Mater Med,2004,15:825-830
23 李清刚.生物人工肾的研究进展.生物医学工程与临床杂志,2001,5(1):39-42
24 Ikuchi A,Okano T.Nanostructured designs of biomedical materials:applications of cell sheet engineering to functional regenerative tissues and organs.J Control Releas,2005;101(1-3):69-84
1 Humes HD.The bioartificial tubule assist device:prospects to improve supportive care in acute renal failure.Ren Fail,1996,18(3):405-408
2 Klenzak J,Himmelfarb J.Sepsis and the kidney.Crit Care Clin,2005,21(2):211-222
3 Webster TJ,Ergun C,Doremus RH,et al.Specific protein mediate enhanced obteoblast adhesion on nanophase ceramics.J Biomed Mater Res,2000,51(3):475-483
4 Li J,Yu J,Zhao F,et al.Direct electrochemistry of glucose oxidese entrapped in nano-sized gold particles-ionic liquid-N N-dimethylformamide composite folm on glassy carbon electrode and glucose sensing.Anal Chim Acta,2007,587(1):33-40
5 Jena BK,Raj CR.Optical sensing of biomedically important polyionic drugs using nano-sized gold particles.Biosens Bioelectron,2008,23(8):1285-1290
6 Kim HK,Jang JW,Lee CH.Surface modification of implant materials and its effect on attachment and proliferation of bone cell.J Mater Sci Mater Med,2004,15:825-830
7 李清刚.生物人工肾的研究进展.生物医学工程与临床杂志,2001,5(1):39-42
8 Kikuchi A,Okano T.Nanostructured designs of biomedical materials:applications of cell sheet engineering to functional regenerative tissues and organs.J Control Releas.2005;101(1-3):69-84
9 Hallab J,Bundy KJ,Oconnor K,et al.Cell adhesion to biomaterials:correlations between surface change,surface roughness,absorbed protein,and cell morphology.J Long Term Eff Med Implants.1995,5(3):209-231
10 Ludwig T,Kirmse R,Poole K,et al.Probing cellular microenvironments and tissue remodeling by atomic force microscopy.Pflugers Arch.2008;456(1):29-49
11 Hirano Y,Takahashi H,Kumeta M,et al.Nuclear architecture and chromatin dynamics revealed by atomic force microscopy in combination with biochemistry and cell biology.Pflugers Arch.2008;456(1):139-153
12 Hillebrand U,Hausberg M,Lang D,et al.How sreroid hormones act on the endothelium isights by atomic force microscopy.Pflugers Arch.2008;456(1):51-60
13 Valois CR,Silva LP,Azevedo RB.Multiple autoclave cycles affect the surface of rotary nickel-titanium files:an atomic force microscopy study.J Endod,2008;34(7):859-862
14 Vadillo RV,Beveridge TJ,Dutcher JR.Surface viscoelasticity of individual gram-negative bacterial cells measured using atomic force microscopy.J Bacteriol,2008;190(12):4225-5232
15 Tiranathanagul K,Eiam OS,Humes HD,et al.The future of renal support high-flux dialysis to bioartificial kidneys.Crit Care Clin,2005,21:379-394
16 Humes HD,Szczpkq MS.Advances in cell therapy for renal failure.Transpl Immunol.2004,12:219-227
17 Humes HD,Fissell WH.The future of hemodialysis membranes.Kidney Int.,2006,69:1115-1119
18 Klenzak J,Himmelfarb J.Sepsis and the kidney.Crit Care Clin,2005,21(2):211-222
19 Fissell WH,Lou L,Abrishami S.Bioartificial kidney ameliorates gram-negative bacteria induced septic shock in uremic animals.J Am Soc Nephrol,2003,14:454-461
20 Fissell WH,Manley S,Westover AJ,et al.Differentiated growth of human renal tubule cells on thin film and nanostructured materials.ASAIO J,2006,52:221-227
21 Gu HY,Chen Z,Sa RX,et al.The immobilization of hepatocytes on 24nm-sized gold colloid for enhanced hepatocytes proliferation.Biomaterials.2004;25(17):3445.3451
22 Gong X,Lu Y,Yu J,et al.Polysulphone microcapsules containing silicone oil for the removal of toxic volatile organics from water,J Micoencapsulation 2008;25(3):196-202
23 Jena BK,Raj CR.Optical sensing of biomedically important polyionic drugs using nano-sized gold particles.Biosens Bioelectron,2008,23(8):1285-1290
24 Zhang W,Li G..Third-generation biosensors based on the direct electron transfer of protein.Anal Sci.2004;20(4):603-609
25 Liu YJ,Nie LH,Tao WY,et al.Amperometric study of Au-colloid function on xanthine biosensors based on xanthine oxidase immobililized in polypyrrole layer.Electroanalysis.2004;16(15):1271-1278
26 王中林编.纳米材料表征.北京:化学工业出版社,2005:245-256
27 倪星元,沈军,张志华.纳米材料的理化特性与应用.北京:化学工业出版社,2005:32-35
28 徐国财,张立德.纳米复合材料.北京:化学工业出版社,2002:9-18
1 Li J,Yu J,Zhao F,et al.Direct electrochemistry of glucose oxidese entrapped in nano-sized gold particles-ionic liquid-N N-dimethylformamide composite folm on glassy carbon electrode and glucose sensing.Anal Chim Acta,2007,587(1):33-40
2 Jena BK,Raj CR.Optical sensing of biomedically important polyionic drugs using nano-sized gold particles.Biosens Bioelectron,2008,23(8):1285-1290
3 Kim HK,Jang JW,Lee CH.Surface modification of implant materials and its effect on attachment and proliferation of bone cell.J Mater Sci Mater Med,2004,15:825-830
4 李清刚.生物人工肾的研究进展.生物医学工程与临床杂志,2001,5(1):39-42
5 徐国财,张立德.纳米复合材料.北京:化学工业出版社,2002:9-18
6 Kikuchi A,Okano T.Nanostructured designs of biomedical materials:applications of cell sheet engineering to functional regenerative tissues and organs.J Control Releas.2005;101(1-3 ):69-84
7 Hallab NJ,Bundy KJ,Oconnor K,et al.Cell adhesion to biomaterials:correlations between surface change,surface roughness,absorbed protein,and cell morphology.J Long Term Eff Med Implants.1995,5(3):209-231
8 Webster TJ,Ergun C,Doremus RH,et al.Specific protein mediate enhanced obteoblast adhesion on nanophase ceramics.J Biomed Mater Res,2000,51(3):475-483
9 Giancotti FG,Ruoaslahti E,Elevated levels of the alpha 5 betal fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cell.Cell,1990,60(5):849-859
10 Amirpour ML,Ghosh P,Lackowski WM,et al.Mammalian cell cultures on micropatterned surfaces of weak-acid,polyeletrolyte hyperbranched thin films on gold.Anal Chem 2001,73(7):1560-1566
11 Noh HK,Lee SW,Kim JM,et al.Electrospinning of chitin nanofibers:degradation behavior and cellular response to normal human keratinocytes and fibroblasts.Biomaterials,2006;27(2):3934-3944
12 Zhang W,Li G Third-generation biosensors based on the direct electron transfer of protein.Anal Sci.2004;20(4):603-609
13 Manisha S,Emestro B,Franciea Y,et al.Taxol inhibits endosomal-lysosomal membrane trafficking at two distinct in CV-1 cells.Am J Physiol Cell Physiol,1998,275:1630-1639
14 Katia RK,Multiresolution algorithms for massively parallel molecular dynamics simulations of nanostructured materials.Computer Physics Communication,2000(128):245-247
15 Dunn GA,Brown AF.Alignment of fibroblasts on grooved surfaces described bysimple geometric transformation.J Cell Sci,1986(83):313-340
16 Clark P.Cell behavior on micropatterned surfaces.Biosens.Bioelectron,1994,9:657-661
17 Fissell WH,Manley S,Westover AJ,et al.Differentiated growth of human renal tubule cells on thin film and nanostructured materials.ASAIO J,2006,52:221-227
18 Li J,Yu J,Zhao F,et al.Direct electrochemistry of glucose oxidese entrapped in nano-sized gold particles-ionic liquid-N N-dimethylformamide composite folm on glassy carbon electrode and glucose sensing.Anal Chim Acta,2007,587(1):33-40
1 Wang H,Ma S.The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome.Am J Emerg Med,2008;26(6):711-715
2 Fissell WH,Humes HD,Fleischman AJ,et al.Dialysis and nanotechnology:now,10 years,or never? Blood Purif,2007;25:12-17
3 Humes HD,Mackay SM,FunkeAJ,et al.The bioartifiacial renal tubule assist device to enhance CRRT in acute renal failure.Ren Fail,1996,18:405-408
4 Humes HD,Mackay SM,Funke AJ,et al.Tissue engineering of a bioartificial renal tubule assist device:In vitro transport and metabolic characteristics.Kidney Int,1999,55:2502-2514
5 Yiranathanagul K,Dhawan V,Lytle IF,et al.Tissue engineering of an implantable bioartificial hemofilter.ASAIO J,2007;53:176-186
6 Tumlin J,Wali R,Williams W,et al.Efficacy and safety of renal tubule cell therapy for acute renal failure.J Am Soc Nephrol,2008;19:1034-1040
7 Issa N,Messer J,Paganini EP.Renal assist device and treatment of sepsis-induced acute kidney injury in intensive care units.Contrib Nephrol,2007;156:419-427
8 董兴刚,陈江华,何强.生物人工肾小管10年回顾与展望。国际移植和血液净化杂志,2008,6:41-42
9 董兴刚,陈江华,何强,等.血滤器的中空纤维聚砜膜的形态学观察方法的探讨和评价.科技通报,2008,24:636-640
10 Li L,Pan J,YU Y.Development of sorbent therapy for multiple organ dysfunction syndrome.Biomed Mater.2007;2(2):R12-16
11 Fissell WH,Fleischman AJ,Humes HD,et al.Development of continuous implantable renal replacement:past and future.Transl Res,2007,150:327-336
12 Humes HD.Fissell WH.Tiranathanagul K.The future of hemodialvsis membranes.Kidney Int.2006,69:1115-1119
13 Tiranathanagul K,Eiam OS,Humes HD,et al.The future of renal support high-flux dialysis to bioartificial kidneys.Crit Care Clin,2005,21:379-394
14 Fissell WH,Manley S,Westover AJ,,et al.Differentiated growth of human renal tubule cells on thin film and nanostructured materials.ASAIO J,2006,52:221-227
15 应旭昱,王笑云,沈霞.生物人工肾小管体外构建及对氨基酸、钠离子、肌酐转运功能的研究.中华肾脏病杂志,2004,20(4):118-121
16 Fissell WH,Lou L,Abrishami S.Bioartificial kidney ameliorates gram-negative bacteria induced septic shock in uremic animals.J Am Soc Nephrol,2003,14:454-461
17 Humes HD,Weitzel WF,Bartlett RH,et al.Initial clinical results of the bioartificial kidney containing human cells in ICU patients with acute renal failure.Kidney Int.,2004,66:1578-1588
18 Humes HD,Weitzel WF,Fissell WH,et al.Renal cell therapy in the treatment of patients with acute and chronic renal failure.Blood Purif,2004,22:60-72
1.Humes HD.Ren Fail,1996,18:405-408
2.Klenzak J,Himmelfarb J.Crit Care Clin,2005,21:211-222
3.Fissell WH,Dyke DB,Weitzel WF,et al.Blood Purif,2002,20:55-60
4.Humes HD.Trans Am Clin Climatol Assoc,2005,116:167-183;discussion 183-184
5.Fissell WH,Lou L,Abrishami S.J Am Soc Nephrol,2003,14:454-461
6.Humes HD,Weitzel WF,Fissell WH,et al.Blood Purif,2004,22:60-72
7.Tiranathanagul K,Eiam OS,Humes HD,et al.Crit Care Clin,2005,21:379-394
8.Humes HD,Szczpkq MS.Transpl Immunol.2004,12:219-227
9.Humes HD,Weitzel WF,Bartlett RH,et al.Kidney Int.,2004,66:1578-1588
10.Szczpkq MS,Westover AJ,Clouthier SG,et al.Stem Cells,2005,23:44-54
11.Brodie Jc,Humes HD.Pharmacol Rev,2005,57:299-313
12.Humes HD,Weitzel WF,Bartlett RH,et al.Blood Purif,2003,21:64-71
13.Humes HD,Fissell WH.Kidney Int.,2006,69:1115-1119
14.Fissell WH,Manley S,Westover AJ,,et al.ASAIO J,2006,52:221-227
1 Humes HD.The bioartificial tubule assist device:prospects to improve supportive care in acute renal failure.Ren Fail,1996,18(3):405-408
2 Klenzak J,Himmelfarb J.Sepsis and the kidney.Crit Care Clin,2005,21(2):211-222
3 Fissell WH,Dyke DB,Weitzel WF,et al.Bioartificial kidney alters cytokine response and hemodynamics in endotoxin-challenged uremic animals.Blood Purif,2002,20:55-60
4 Humes HD.Stem cells:The next therapeutic frontier.Trans Am Clin Climatol Assoc,2005,116:167-183;discussion 183-184
5 Fissell WH,Lou L,Abrishami S.Bioartificial kidney ameliorates gram-negative bacteria induced septic shock in uremic animals.J Am Soc Nephrol,2003,14:454-461
6 Humes HD,Weitzel WF,Fissell WH,et al.Renal cell therapy in the treatment of patients with acute and chronic renal failure.Blood Purif,2004,22:60-72
7 Tiranathanagul K,Eiam OS,Humes HD,et al.The future of renal support high-flux dialysis to bioartificial kidneys.Crit Care Clin,2005,21:379-394
8 Humes HD,Szczpkq MS.Advances in cell therapy for renal failure.Transpl Immunol.2004,12:219-227
9 Humes HD,Weitzel WF,Bartlett RH,et al.Initial clinical results of the bioartificial kidney containing human cells in ICU patients with acute renal failure.Kidney Int.,2004,66:1578-1588
10 Szczpkq MS,Westover AJ,Clouthier SG,et al.Rare incorporation of bone marrow cells into kidney after folic acid-induced injury.Stem Cells,2005,23:44-54
11 Brodie Jc,Humes HD.Stem cell approaches for the treatment of renal failure.Pharmacol Rev,2005,57:299-313
12 Humes HD,Weitzel WF,Bartlett RH,et al.Renal cell therapy is associated with dynamic and individualized responses in patients with acute renal failure.Blood Purif,2003,21:64-71
13 Humes HD,Fissell WH.The future of hemodialysis membranes.Kidney Int.,2006,69:1115-1119
14 Fissell WH,Manley S,Westover AJ,,et al.Differentiated growth of human renal tubule cells on thin film and nanostructured materials.ASAIO J,2006,52:221-227
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