Microfluidic chip-based synthesis of alginate microspheres for encapsulation of immortalized human cells.

Cellular transplantation is a promising technology with great clinical potential in regenerative medicine and disease management. However, effective control over patient immunological response is essential. The encapsulation of cells within hydrogel microspheres is an increasingly prevalent method for the protection of cellular grafts from immune rejection. Microfluidic "chip" reactors present elegant solutions to several capsule generation issues, including the requirement for intercapsule uniformity, high reproducibility, and sterile, good manufacturing practice compliance. This study presents a novel method for the on-chip production of stable, highly monodisperse alginate microspheres and demonstrates its utility in the encapsulation of an immortalized human-derived cell line. Four populations of immortalized human embryonic kidney cells (HEK293) were encapsulated on chip within monodisperse alginate capsules. Cell viability measurements were recorded for each of the four encapsulated populations for 90 days.

[1]  Stephen Mann,et al.  Strategies to promote chondrogenesis and osteogenesis from human bone marrow cells and articular chondrocytes encapsulated in polysaccharide templates. , 2006, Tissue engineering.

[2]  Ethan Tumarkin,et al.  Microfluidic production of biopolymer microcapsules with controlled morphology. , 2006, Journal of the American Chemical Society.

[3]  Keng-Shiang Huang,et al.  Manipulating the generation of Ca-alginate microspheres using microfluidic channels as a carrier of gold nanoparticles. , 2006, Lab on a chip.

[4]  Y. Xiong,et al.  Microencapsulated nerve growth factor-expressing NIH3T3 cells-incorporated tissue engineering skin: a preliminary study. , 2006, Singapore medical journal.

[5]  H. Iwata,et al.  Induction dopamine releasing cells from mouse embryonic stem cells and their long-term culture. , 2006, Journal of biomedical materials research. Part A.

[6]  J. Xu,et al.  Microencapsulating hepatocytes. , 2005, Transplantation proceedings.

[7]  D. Beebe,et al.  Controlled microfluidic interfaces , 2005, Nature.

[8]  Armand Ajdari,et al.  Droplet Control for Microfluidics , 2005, Science.

[9]  G. Weir,et al.  Long-Term Normoglycemia in Rats Receiving Transplants with Encapsulated Islets , 2005, Transplantation.

[10]  T. Cheng,et al.  Differentiation of dermis-derived multipotent cells into insulin-producing pancreatic cells in vitro. , 2004, World journal of gastroenterology.

[11]  Tatsuo Maruyama,et al.  Liquid membrane operations in a microfluidic device for selective separation of metal ions. , 2004, Analytical chemistry.

[12]  Giovanni Luca,et al.  Grafts of microencapsulated pancreatic islet cells for the therapy of diabetes mellitus in non‐immunosuppressed animals , 2004, Biotechnology and applied biochemistry.

[13]  Takehiko Kitamori,et al.  Three-layer flow membrane system on a microchip for investigation of molecular transport. , 2002, Analytical chemistry.

[14]  S. Pérez,et al.  Molecular basis of C(2+)-induced gelation in alginates and pectins: the egg-box model revisited. , 2001, Biomacromolecules.

[15]  A. Fournier,et al.  Production of alginate beads by emulsification/internal gelation. I. Methodology , 1992, Applied Microbiology and Biotechnology.

[16]  H. Kataoka,et al.  Effective oxygenation of immobilized cells through reduction in bead diameters: a review , 1991 .

[17]  Giovanni Luca,et al.  Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes: first two cases. , 2006, Diabetes care.

[18]  Wei Wang,et al.  Proliferation and Differentiation of Mouse Embryonic Stem Cells in APA Microcapsule: A Model for Studying the Interaction between Stem Cells and Their Niche , 2006, Biotechnology progress.

[19]  C. Heinzen,et al.  Alginate encapsulation of genetically engineered mammalian cells: comparison of production devices, methods and microcapsule characteristics. , 2003, Journal of microencapsulation.