Benefits of flow cultures

Culturing tissues and organs in-vitro to replace those that have been damaged by disease or trauma is the main aim of Tissue Engineering. Achieving this goal will bring a huge amount of benefits for the patients since it will suppose an enormous advance with respect to the actual treatments, based on the transplantation of autologous, xenologous and allogous tissues and organs.

Although transplantations have shown pretty effective, they carry many important disadvantages related to the limited number of donors, compatibility issues and the very expensive social and economic costs.

Tissue Engineering promises to revolution the actual treatments though, nevertheless, it is still facing some crucial issues regarding the culture of cells in-vitro. Specifically, the obtaining of culturing conditions in the laboratory which accurately mimic the in-vivo growing conditions is one of the crucial challenges to tackle.

Among those conditions, the reproduction of an "artificial" vascular system able to supply the growing cells with sufficient oxygen and nutrients, as well as to remove the waste matter generated by cells metabolism, is one of the most difficult issues.

Cell cultures developed on three-dimensional scaffolds in a still culture medium are specially sensitive to this fact. Assuming that oxygen and nutrients are equally distributed across the volume of the scaffold at the beginning of the culture, cells should develop at a similar rate in the whole scaffold. However, those cells located at the center of the scaffold transform oxygen and nutrients in carbon dioxide and waste matter soon, since renovation rate by unforced diffusion is too slow compared to cell metabolism. Then, it is found that scaffolds larger than 1 mm typically result in shell of viable cells and matrix surrounding a necrotic core due to the absence of vascular supply.

Thus, the improvement of mass transport and nutrient exchange in three-dimensional in-vitro experiments is crucial to get viable cells populations, for which the imposing of certain flow rate the culture media across the scaffold (perfusion) has been experimentally shown very efficacious compared to static cultures.

Likewise, flow stimulation is also crucial for the appropriate development of certain kinds of tissue as, for instance, the vascular tissue. In this case, endothelial cells in the intimal layer are strongly influence by the effect of blood flow, which has been experimentally demonstrated to exert a strong influence of the behaviour of such cells and, in general, of the whole vessel. Thus, culturing of blood vessels under flow conditions is of vital importance, since no other conditions better reproduce conditions experienced by cells in-vivo.