Biofabrication of microcapsules encapsulating beta-TC-6 cells via scalable device and in-vivo evaluation in type 1 diabetic mice

被引:10
作者
Bansal, Amit [1 ,2 ]
D'Sa, Sucheta [1 ,3 ]
D'Souza, Martin J. [1 ]
机构
[1] Mercer Univ, Coll Pharm, Ctr Drug Delivery Res, Vaccine Nanotechnol Lab, Atlanta, GA 30341 USA
[2] Formulat R&D, Plant 4, Allegan, MI 49010 USA
[3] Dept Analyt Chem, Charles River Labs, Ashland, OH 44805 USA
关键词
Cell microencapsulation; Spraying nozzle; Alginate; Transplantation; Cell viability; ALGINATE-CHITOSAN; ISLET CELLS; MICROENCAPSULATION; TRANSPLANTATION; MEMBRANE; IMMUNOISOLATION; MICROPARTICLES; EXPRESSION; PROTECTION; SYSTEM;
D O I
10.1016/j.ijpharm.2019.118830
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Type 1 diabetes mellitus (T1DM) is a disease characterized by lack of pancreatic islet function. Whole tissue transplantation appears to be a viable alternative in the management of T1DM. This study aims at the fabrication and evaluation of alginate-chitosan microcapsules encapsulating insulin-secreting beta-TC-6 cells using an automated spraying nozzle. Uniform spherical microcapsules (250-350 mu m) encapsulated with beta-TC-6 cells were fabricated in large quantities in a short span of time. Microencapsulated beta-TC-6 cells were transplanted intraperitoneally into streptozotocin (STZ) induced diabetic mice and monitored for immune tolerance and decrease in blood glucose levels. Mice that received microencapsulated beta-TC-6 cells maintained normoglycemia for 35 +/- 5 days before rejection. However, the group that received naked beta-TC-6 cells rejected the cells within 1-2 days, unable to control elevated blood glucose levels. They also exhibited high immune reactions, as evidenced by elevated levels of CDS+ and CD62L T cells. CD4(+) T cells that mediated a Th2 response (humoral response) were predominant in microencapsulated beta-TC-6 cells and cells only group as evidenced by elevated levels of CD45R. Our findings from the in-vivo study demonstrated that transplantation of microencapsulated beta-TC-6 cells can be a viable alternative in the management of T1DM with acceptable immune response.
引用
收藏
页数:11
相关论文
共 50 条
[1]
Alginate-chitosan complex coacervation for cell encapsulation: Effect on mechanical properties and on long-term viability [J].
Baruch, Limor ;
Machluf, Marcelle .
BIOPOLYMERS, 2006, 82 (06) :570-579
[2]
Effect of calcium and/or barium crosslinking on the physical and antimicrobial properties of natamycin-loaded alginate films [J].
Bierhalz, Andrea C. K. ;
da Silva, Mariana A. ;
Braga, Mara E. M. ;
Sousa, Herminio J. C. ;
Kieckbusch, Theo G. .
LWT-FOOD SCIENCE AND TECHNOLOGY, 2014, 57 (02) :494-501
[3]
Improved activity of streptozotocin-selected insulinoma cells following microencapsulation and transplantation into diabetic mice [J].
Bloch, K ;
Vorobeychik, M ;
Yavrians, K ;
Azarov, D ;
Bloch, O ;
Vardi, P .
CELL BIOLOGY INTERNATIONAL, 2006, 30 (02) :138-143
[4]
IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice [J].
Cardozo, AK ;
Proost, P ;
Gysemans, C ;
Chen, MC ;
Mathieu, C ;
Eizirik, DL .
DIABETOLOGIA, 2003, 46 (02) :255-266
[5]
A new microencapsulation device for controlled membrane and capsule size distributions [J].
Ceausoglu, I ;
Hunkeler, D .
JOURNAL OF MICROENCAPSULATION, 2002, 19 (06) :725-735
[6]
Protection of insulin secreting cells from nitric oxide induced cellular damage by crosslinked hemoglobin [J].
Chae, SY ;
Lee, M ;
Kim, SW ;
Bae, YH .
BIOMATERIALS, 2004, 25 (05) :843-850
[7]
Droplet-based microfluidic platforms for the encapsulation and screening of mammalian cells and multicellular organisms [J].
Clausell-Tormos, Jenifer ;
Lieber, Diana ;
Baret, Jean-Christophe ;
El-Harrak, Abdeslam ;
Miller, Oliver J. ;
Frenz, Lucas ;
Blouwolff, Joshua ;
Humphry, Katherine J. ;
Koster, Sarah ;
Duan, Honey ;
Holtze, Christian ;
Weitz, David A. ;
Griffiths, Andrew D. ;
Merten, Christoph A. .
CHEMISTRY & BIOLOGY, 2008, 15 (05) :427-437
[8]
Long-Term Metabolic Control of Autoimmune Diabetes in Spontaneously Diabetic Nonobese Diabetic Mice by Nonvascularized Microencapsulated Adult Porcine Islets [J].
Cui, Hong ;
Tucker-Burden, Carol ;
Cauffiel, Sean M. D. ;
Barry, Adrienne K. ;
Iwakoshi, Neal N. ;
Weber, Collin J. ;
Safley, Susan A. .
TRANSPLANTATION, 2009, 88 (02) :160-169
[9]
A membrane-mimetic barrier for islet encapsulation [J].
Cui, W ;
Barr, G ;
Faucher, KM ;
Sun, XL ;
Safley, SA ;
Weber, CJ ;
Chaikof, EL .
TRANSPLANTATION PROCEEDINGS, 2004, 36 (04) :1206-1208
[10]
Microcapsules and their ability to protect islets against cytokine-mediated dysfunction [J].
de Groot, M ;
Keizer, PPM ;
de Haan, BJ ;
Schuurs, TA ;
Leuvenink, HGD ;
van Schilfgaarde, R ;
de Vos, P .
TRANSPLANTATION PROCEEDINGS, 2001, 33 (1-2) :1711-1712