Trends in cell culture technology.

Dynamic macroscale bioreactor systems are the most recent breakthrough in cell culture technology. This major achievement, at the beginning of the 21st century, fortunately coincided with an embarrassing gap in the measures to predict the safety and modes of action of chemicals, cosmetics, air particles and pharmaceuticals. The major hurdles to the translation of these breakthrough achievements of cell culture technology into meaningful solutions for predictive high throughput substance testing remain miniaturization from the milliliter to the microliter scale and the supply of relevant amounts of standardized human tissue. This chapter provides insights into the latest developments in this area, illustrates an original multi-micro-organ bioreactor concept and identifies highways for closing the gap.

[1]  Carla F. Kim,et al.  Paving the road for lung stem cell biology: bronchioalveolar stem cells and other putative distal lung stem cells. , 2007, American journal of physiology. Lung cellular and molecular physiology.

[2]  E. Clair,et al.  The calm after the cytokine storm: lessons from the TGN1412 trial , 2008 .

[3]  L. Lajtha,et al.  Proliferation of Haemopoietic Stem Cells in Vitro , 1974, British journal of haematology.

[4]  Uwe Marx,et al.  A human lymph node in vitro--challenges and progress. , 2006, Artificial organs.

[5]  I M Sauer,et al.  Clinical extracorporeal hybrid liver support – phase I study with primary porcine liver cells , 2003, Xenotransplantation.

[6]  Thaddeus S Stappenbeck,et al.  Deciphering the ‘black box’ of the intestinal stem cell niche: taking direction from other systems , 2008, Current opinion in gastroenterology.

[7]  P. Neuhaus,et al.  Extracorporeal liver support based on primary human liver cells and albumin dialysis--treatment of a patient with primary graft non-function. , 2003, Journal of hepatology.

[8]  C. Simmons,et al.  Matrix-dependent adhesion of vascular and valvular endothelial cells in microfluidic channels. , 2007, Lab on a chip.

[9]  Jan Hansmann,et al.  Engineered liver-like tissue on a capillarized matrix for applied research. , 2007, Tissue engineering.

[10]  L. Griffith,et al.  Functional behavior of primary rat liver cells in a three-dimensional perfused microarray bioreactor. , 2002, Tissue engineering.

[11]  A. Can,et al.  Haematopoietic stem cells niches: interrelations between structure and function. , 2008, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[12]  L. Griffith,et al.  A microfabricated array bioreactor for perfused 3D liver culture. , 2002, Biotechnology and bioengineering.

[13]  Utpal Banerjee,et al.  The hematopoietic stem cell and its niche: a comparative view. , 2007, Genes & development.

[14]  L. Griffith,et al.  Capturing complex 3D tissue physiology in vitro , 2006, Nature Reviews Molecular Cell Biology.

[15]  Satoru Takeda,et al.  In vitro formation of capillary networks using optical lithographic techniques. , 2007, Biochemical and biophysical research communications.

[16]  A. Wheeler,et al.  Digital microfluidics for cell-based assays. , 2008, Lab on a chip.

[17]  Hanry Yu,et al.  Perfusion culture improves the maintenance of cultured liver tissue slices. , 2007, Tissue engineering.

[18]  H B Fell,et al.  The growth, development and phosphatase activity of embryonic avian femora and limb-buds cultivated in vitro. , 1929, The Biochemical journal.

[19]  Takehiko Kitamori,et al.  Biological cells on microchips: new technologies and applications. , 2007, Biosensors & bioelectronics.

[20]  E. Drapeau,et al.  Brain micro-ecologies: neural stem cell niches in the adult mammalian brain , 2008, Philosophical Transactions of the Royal Society B: Biological Sciences.

[21]  J. Encke,et al.  Hepatocyte Culture between Three Dimensionally Arranged Biomatrix-Coated Independent Artificial Capillary Systems and Sinusoidal Endothelial Cell Co-Culture Compartments , 1994, The International journal of artificial organs.

[22]  J. Gerlach,et al.  Bioreactors for Liver Tissue , 2007 .

[23]  I M Sauer,et al.  Primary Human Liver Cells as Source for Modular Extracorporeal Liver Support - a Preliminary Report , 2002, The International journal of artificial organs.

[24]  Thorsten Walles,et al.  Engineering of a vascularized scaffold for artificial tissue and organ generation. , 2005, Biomaterials.

[25]  L. Samson,et al.  A microscale in vitro physiological model of the liver: predictive screens for drug metabolism and enzyme induction. , 2005, Current drug metabolism.

[26]  Michael Fischer,et al.  Microcavity array (MCA)-based biosensor chip for functional drug screening of 3D tissue models. , 2008, Biosensors & bioelectronics.

[27]  Ralf Paus,et al.  Immunophenotyping of the human bulge region: the quest to define useful in situ markers for human epithelial hair follicle stem cells and their niche , 2008, Experimental dermatology.

[28]  Melba Navarro,et al.  Nanotechnology in regenerative medicine: the materials side. , 2008, Trends in biotechnology.

[29]  G. Moore,et al.  Kinetics of gas diffusion in mammalian cell culture systems. I. Experimental , 1968 .

[30]  Linheng Li,et al.  The stem cell niches in bone. , 2006, The Journal of clinical investigation.

[31]  A. Wagers,et al.  No place like home: anatomy and function of the stem cell niche , 2008, Nature Reviews Molecular Cell Biology.

[32]  Uwe Marx,et al.  Drug testing in vitro : breakthroughs and trends in cell culture technology , 2006 .

[33]  Alexis Carrel,et al.  ON THE PERMANENT LIFE OF TISSUES OUTSIDE OF THE ORGANISM , 1912, The Journal of experimental medicine.