Growing tissues in microgravity

Unsworth, Brian R.; Lelkes, Peter I.

doi:10.1038/nm0898-901

Cited by 360 publications

(271 citation statements)

References 58 publications

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“…The combination of these two culture variables yielded the greatest response, with the islet-DEC aggregates held within the RCCS showing both preserved morphology and functional integrity for up to 10 days post isolation. It is likely that the simulated micro-gravity environment created within the RCCS [27] permits a greater degree of physiologically appropriate cell-cell contact and signalling, and as the cells are in a constant state of free-fall, the opportunity for islet exposure to soluble duct-derived trophic factors is enhanced. This isletprotecting effect of the DECs is also reflected in the insulin Values represent the mean ratio of total insulin (ng) to total protein (µg) at the time point tested.…”

Section: Discussionmentioning

confidence: 99%

Sustained insulin secretory response in human islets co-cultured with pancreatic duct-derived epithelial cells within a rotational cell culture system

et al. 2009

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Aims/hypothesis Loss of the trophic support provided by surrounding non-endocrine pancreatic cell populations underlies the decline in beta cell mass and insulin secretory function observed in human islets following isolation and culture. This study sought to determine whether restoration of regulatory influences mediated by ductal epithelial cells promotes sustained beta cell function in vitro. Methods Human islets were isolated according to existing protocols. Ductal epithelial cells were harvested from the exocrine tissue remaining after islet isolation, expanded in monolayer culture and characterised using fluorescence immunocytochemistry. The two cell types were co-cultured under conventional static culture conditions or within a rotational cell culture system. The effect of co-culture on islet structural integrity, beta cell mass and insulin secretory capacity was observed for 10 days following isolation. Results Human islets maintained under conventional culture conditions exhibited a characteristic loss in structural integrity and functional viability as indicated by a diminution of glucose responsiveness. By contrast, co-culture of islets with ductal epithelial cells led to preserved islet morphology and sustained beta cell function, most evident in co-cultures held within the rotational cell culture system, which showed a significantly (p<0.05) greater insulin secretory response to elevated glucose compared with control islets. Similarly, insulin/protein ratio data suggested that the presence of ductal epithelial cells is beneficial for the maintenance of beta cell mass. Conclusions/interpretation The data indicate a supportive role for ductal epithelial cells in islet viability. Further characterisation of the regulatory influences may lead to novel strategies to improve long-term beta cell function both in vitro and following islet transplantation.

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Section: Discussionmentioning

confidence: 99%

Sustained insulin secretory response in human islets co-cultured with pancreatic duct-derived epithelial cells within a rotational cell culture system

et al. 2009

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“…Again, such modalities are at an experimental stage, and their applicability remains to be confirmed. [67][68][69][70][71][72] …”

Section: Novel Culture Modalitiesmentioning

confidence: 99%

Which hepatocyte will it be? Hepatocyte choice for bioartificial liver support systems

Tsiaoussis

Newsome

Nelson

et al. 2001

Liver Transplantation

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Liver failure, notwithstanding advances in medical management, remains a cause of considerable morbidity and mortality in the developed world. Although bioartificial liver (BAL) support systems offer the potential of significant therapeutic benefit for such patients, many issues relating to their use are still to be resolved. In this review, these issues are examined in terms of the functions required, the cells of choice in such a system, and the most appropriate environment to optimize the function of such cells T he development of nonbiological systems to support critically ill patients with acute liver failure (ALF) that incorporate plasmapheresis, 1 charcoal hemoperfusion, 2 and ultrafiltration techniques 3 has not had a significant impact on survival. Consequently, hepatocytebased biological systems have attracted intense interest worldwide but have also generated most of the controversy. Uncertainty exists about the most suitable biological component and the risk for zoonoses and immune rejection in the host. In addition, the optimization of culture conditions and thus metabolic function of the biological component have not been systematically studied, although continuing improvements in these areas have rendered this therapeutic avenue in ALF more promising. To compound matters, the question of which aspects of hepatocyte metabolism in an artificial liver are required to sustain life and promote recovery remains largely unanswered, further limiting development. In this review, the biological substrate of such systems is critically examined and insights are provided into the ideal system.

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“…Among these, the rotary wall vessel (RWV) bioreactor particularly has been demonstrated to enhance the production of cartilage matrix in different scaffold cultures 12,13 . In RWV bioreactors, engineered constructs encounter a simulated microgravity environment because its free-fall is counteracted by the upward force of medium rotation 14,15 . Also, the rotation of culture medium exerts mechanical stimulus on the cells within the construct, and enhances the exchange of nutrients, oxygen, and metabolic wastes.…”

Section: Introductionmentioning

confidence: 99%

Cell–Nanofiber-Based Cartilage Tissue Engineering Using Improved Cell Seeding, Growth Factor, and Bioreactor Technologies

Jiang

Tuan

2008

Tissue Engineering Part A

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Biodegradable nanofibrous scaffolds serving as an extracellular matrix substitute have been shown to be applicable for cartilage tissue engineering. However, a key challenge in using nanofibrous scaffolds for tissue engineering is that the small pore size limits the infiltration of cells, which may result in uneven cell distribution throughout the scaffold. This study describes an effective method of chondrocyte loading into nanofibrous scaffolds, which combines cell seeding, mixing, and centrifugation to form homogeneous, packed cell-nanofiber composites (CNCs). When the effects of different growth factors are compared, CNCs cultured in medium containing a combination of insulin-like growth factor-I and transforming growth factor-β1 express the highest mRNA levels of collagen type II and aggrecan. Radiolabeling analyses confirm the effect on collagen and sulfated-glycosaminoglycans (sGAG) production. Histology reveals chondrocytes with typical morphology embedded in lacuna-like space throughout the entire structure of the CNC. Upon culturing using a rotary wall vessel bioreactor, CNCs develop into a smooth, glossy cartilage-like tissue, compared to a rough-surface tissue when maintained in a static environment. Bioreactorgrown cartilage constructs produce more total collagen and sGAG, resulting in greater gain in net tissue weight, as well as express cartilage-associated genes, including collagen types II and IX, cartilage oligomeric matrix protein, and aggrecan. In addition, dynamic culture enhances the mechanical property of the engineered cartilage. Taken together, these results indicate the applicability of nanofibrous scaffolds, combined with efficient cell loading and bioreactor technology, for cell-based cartilage tissue engineering.

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Growing tissues in microgravity

Cited by 360 publications

References 58 publications

Sustained insulin secretory response in human islets co-cultured with pancreatic duct-derived epithelial cells within a rotational cell culture system

Sustained insulin secretory response in human islets co-cultured with pancreatic duct-derived epithelial cells within a rotational cell culture system

Which hepatocyte will it be? Hepatocyte choice for bioartificial liver support systems

Cell–Nanofiber-Based Cartilage Tissue Engineering Using Improved Cell Seeding, Growth Factor, and Bioreactor Technologies

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