Biomimicking Robust Hydrogel for the Mesenchymal Stem Cell Carrier

被引:6
作者
Oh, Byeongtaek [1 ]
Melchert, Russell B. [2 ]
Lee, Chi H. [1 ,3 ]
机构
[1] Univ Missouri, Sch Pharm, Div Pharmaceut Sci, Kansas City, MO 64108 USA
[2] Univ Missouri, Sch Pharm, Div Pharmacol & Toxicol, Kansas City, MO 64108 USA
[3] Univ Missouri, Div Pharmaceut Sci, Kansas City, MO 64108 USA
关键词
biomimicking hydrogel-nanofiber; coating of drug eluting stent; immunomodulatory effects; mesenchymal stem cells; REGULATORY T-CELLS; INDOLEAMINE 2,3-DIOXYGENASE; MOUSE MODEL; CALCIUM; ALGINATE; IMMUNOMODULATION; DIFFERENTIATION; INDUCTION; NANOFIBER; BIOFILMS;
D O I
10.1007/s11095-015-1698-y
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
This study was aimed to develop a hydrogel-nanofiber as an advanced carrier for adipose derived human mesenchymal stem cells (AD-MSCs) and evaluate its potential for immunomodulatory therapies applicable to surface coating of drug eluting stent (DES) against coronary artery diseases (CAD). A mixture of dispersing-nanofibers (dNFs) and poly (ethylene glycol)-diacrylate (PEGDA) were blended with sodium alginate to achieve robust mechanical strength. The effects of stem cell niche on cell viability and proliferation rates were evaluated using LDH assay and alamar blue assay, respectively. The amount of Nile-red microparticles (NR-MPs) remained in the hydrogel scaffolds was examined as an index for the physical strength of hydrogels. To evaluate the immunomodulatory activity of AD-MSCs as well as their influence by ROS, the level of (L)-Kynurenine was determined as tryptophan replacement compounds in parallel with IDO secreted from AD-MSCs using a colorimetric assay of (L)-amino acid. Both SA-cys-PEG and SA-cys-dNF-PEG upon being coated on stents using electrophoretic deposition technique displayed superior mechanical properties against the perfused flow. d-NFs had a significant impact on the stability of SA-cys-dNF-PEG, as evidenced by the substantial amount of NR-MPs remained in them. An enhanced subcellular level of ROS by spheroidal cluster yielded the high concentrations of (L)-Kynurenine (1.67 +/- 0.6 mu M without H2O2, 5.2 +/- 1.14 mu M with 50 mu M of H2O2 and 8.8 +/- 0.51 mu M with 100 mu M of H2O2), supporting the IDO-mediated tryptophan replacement process. The "mud-and-straw" hydrogels are robust in mechanical property and can serve as an ideal niche for AD-MSCs with immunomodulatory effects.
引用
收藏
页码:3213 / 3227
页数:15
相关论文
共 51 条
[1]   Immunomodulation by mesenchymal stem cells - A potential therapeutic strategy for type 1 diabetes [J].
Abdi, Reza ;
Fiorina, Paolo ;
Adra, Chaker N. ;
Atkinson, Mark ;
Sayegh, Mohamed H. .
DIABETES, 2008, 57 (07) :1759-1767
[2]   Nanospiderwebs: Artificial 3D Extracellular Matrix from Nanofibers by Novel Clinical Grade Electrospinning for Stem Cell Delivery [J].
Alamein, Mohammad A. ;
Liu, Qin ;
Stephens, Sebastien ;
Skabo, Stuart ;
Warnke, Frauke ;
Bourke, Robert ;
Heiner, Peter ;
Warnke, Patrick H. .
ADVANCED HEALTHCARE MATERIALS, 2013, 2 (05) :702-717
[3]   Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids [J].
Ankrum, James A. ;
Dastidar, Riddhi G. ;
Ong, Joon Faii ;
Levy, Oren ;
Karp, Jeffrey M. .
SCIENTIFIC REPORTS, 2014, 4
[4]   A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation [J].
Braun, D ;
Longman, RS ;
Albert, ML .
BLOOD, 2005, 106 (07) :2375-2381
[5]   Mesenchymal Stem Cells Genetically Modified with the Angiopoietin-1 Gene Enhanced Arteriogenesis in a Porcine Model of Chronic Myocardial Ischaemia [J].
Chen, S. L. ;
Zhu, C. C. ;
Liu, Y. Q. ;
Tang, L. J. ;
Yi, L. ;
Yu, B. J. ;
Wang, D. J. .
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2009, 37 (01) :68-78
[6]   Large variations in absolute wall shear stress levels within one species and between species [J].
Cheng, Caroline ;
Helderman, Frank ;
Tempel, Dennie ;
Segers, Dolf ;
Hierck, Beerend ;
Poelmann, Rob ;
van Tol, Arie ;
Duncker, Dirk J. ;
Robbers-Visser, Danielle ;
Ursem, Nicolette T. C. ;
van Haperen, Rien ;
Wentzel, Jolanda J. ;
Gijsen, Frank ;
van der Steen, Anton F. W. ;
de Crom, Rini ;
Krams, Rob .
ATHEROSCLEROSIS, 2007, 195 (02) :225-235
[7]   Electroaddressing Functionalized Polysaccharides as Model Biofilms for Interrogating Cell Signaling [J].
Cheng, Yi ;
Tsao, Chen-Yu ;
Wu, Hsuan-Chen ;
Luo, Xiaolong ;
Terrell, Jessica L. ;
Betz, Jordan ;
Payne, Gregory F. ;
Bentley, William E. ;
Rubloff, Gary W. .
ADVANCED FUNCTIONAL MATERIALS, 2012, 22 (03) :519-528
[8]   Preparation of hydrophilic poly(L-lactide) electrospun fibrous scaffolds modified with chitosan for enhanced cell biocompatibility [J].
Cui, Wenguo ;
Cheng, Liying ;
Li, Haiyan ;
Zhou, Yue ;
Zhang, Yuguang ;
Chang, Jiang .
POLYMER, 2012, 53 (11) :2298-2305
[9]  
De Miguel MP, 2012, CURR MOL MED, V12, P574
[10]   Cell-Based Drug Delivery Devices Using Phagocytosis-Resistant Backpacks [J].
Doshi, Nishit ;
Swiston, Albert J. ;
Gilbert, Jonathan B. ;
Alcaraz, Maria L. ;
Cohen, Robert E. ;
Rubner, Michael F. ;
Mitragotri, Samir .
ADVANCED MATERIALS, 2011, 23 (12) :H105-H109