Trends in Biotechnology
Microscale tissue engineering using gravity-enforced cell assembly
Section snippets
Scaffold-free microtissues – hanging-drop technology revisited
Strategies using natural reaggregation potential to assemble monodispersed cells in a tissue-mimicking way represent a valuable extension of current scaffold-based tissue engineering initiatives. Scaffold-free reaggregation of cells to microtissues can occur following: (i) cultivation in shake flasks, gyratory shakers and roller bottles 13, 14, 15 or on non-adhesive surfaces [16]; (ii) centrifugation-based compression [17]; (iii) maintenance in cell-culture inserts [18]; or (iv)
Design of artificial hepatic tissues
The healthy liver is able to regenerate after injury. However, once damaged by fibrosis and cirrhosis – the result of a variety of chronic conditions, including alcohol abuse or infection with hepatitis virus B or C – the regeneration capacity of the liver is compromised. Liver transplantation is a routine treatment for end-stage liver disease, yet donor organ shortage continues to be a serious problem [26]. The liver has many crucial functions, including the production of clotting factors and
Artificial myocardial microtissue
Heart diseases such as myocardial infarction and heart failure are the most prevalent pathologies in industrialized countries. Loss of cardiomyocytes accounts for decreased myocardial function, which can result in total organ failure or trigger compensatory mechanisms such as hypertrophy of the remaining myocardium, activation of neurohumoral systems and/or autokrine or parakrine stimulation by various growth factors or cytokines [33]. The ultimate treatment of end-stage heart failure is heart
Microcartilage
Osteoarthritis and rheumatoid arthritis – the most prevalent disorders of the musculoskeletal system – result from the disturbance of tissue homeostasis in articular joints, and are diagnosed by joint pain, tenderness, movement limitations, as well as effusion and variable degrees of inflammation. Rheumatoid arthritis is characterized by chondrocytes that produce inflammatory signals and matrix metalloproteinases, which result in thinning of the collagen network, decrease of proteoglycan
Beyond tissue engineering: the future of microtissues in biopharmaceutical manufacturing and high-throughput drug discovery
Monodispersed cells growing in suspension and protein-free media are currently the gold standard for large-scale manufacturing of protein therapeutics [45]. Although key biopharmaceutical manufacturing parameters such as growth rate, cell density and specific productivity can be optimized by advanced bioprocess control or specific molecular interventions in production cell lines, the question remains as to whether specific productivity of suspension cells typically reached in classical
Concluding remarks
‘We are a self-assembling organism. That information is there to be captured and used.’ These were the words of William Haseltine, Chairman and CEO of Human Genome Sciences (http://www.hgsi.com/), who was among the first to coin the term regenerative medicine to describe new ways of teaching the body to heal itself [52]. Microtissue design consisting of reaggregation of biopsy-derived (stem) cell populations or (stem) cell lines harnesses the self-assembling programs of the organism to provide
Acknowledgements
We thank Lars K. Nielsen for providing the micrographs in Figure 3. We also thank David Fluri, Beat P. Kramer and Shizuka Hartenbach for critical comments on the manuscript. Work in the laboratory of M.F. is supported by the Swiss National Science Foundation (Grant No. 631065946).
References (70)
Multicellular tumor spheroids: intermediates between monolayer culture and in vivo tumor
Cell Biol. Int.
(1999)Titanium dioxide ceramics control the differentiated phenotype of cardiac muscle cells in culture
Biomaterials
(2000)Modification of heart valve allografts and xenografts by means of tissue engineering
Transplant. Proc.
(2002)Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects
Osteoarthritis Cartilage
(2002)- et al.
Tissue engineering: advances in in vitro cartilage generation
Trends Biotechnol.
(2002) - et al.
Industrial choices for protein production by large-scale cell culture
Curr. Opin. Biotechnol.
(2001) - et al.
Engineering cellular microenvironments to improve cell-based drug testing
Drug Discov. Today
(2002) Of layers and spheres: the reaggregate approach in tissue engineering
Trends Neurosci.
(2002)Cell sheet engineering for myocardial tissue reconstruction
Biomaterials
(2003)In vitro function of porcine hepatocyte spheroids in 100% human plasma
Cell Transplant.
(1996)