The world is facing a growing crisis as the number of patients on organ donation waiting lists far outpaces the number of adequate organs available for transplantation. Increased vital organ failure in the aging population of the West, twinned with rapidly improving posttransplantation survival rates have served to compound this issue. For example in the US alone, more than 120,000 people are currently on the transplant waiting list; on average 18 people die everyday while waiting for a transplant, and every 10 minutes another name is added to the list1.
An often-cited solution to this growing problem is the promise of Tissue Engineering; the process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function. A basic schematic of a typical Tissue Engineering approach (Figure 1) sees cells isolated from a patients injured tissue and cultivated in the lab before being seeded on a specialised scaffold and re-implanted into the body. Tissue Engineering has received a lot of recent press due to the pioneering advances made by the likes of Robert Langer and Anthony Atala; the latter having successfully tissue engineered bladders and vaginal organs2. The key is to isolate undifferentiated cells, expand them to sufficient quantities and then use a scaffold to direct their differentiation into the cell type of choice. For example, in engineering a blood vessel you might isolate endothelial-progenitor cells to form the inner lining and mesenchymal stem cells for the outer connective tissue. You may then create a cylindrical scaffold that resembles a blood vessel and seed endothelial-progenitors on the inside and mesenchymal stem cells on the outside. If you had created a scaffold that resembled their normal biological environment closely enough, the cells may be ‘tricked’ into forming a new section of blood vessel, which could be implanted into the patient.
Biologists and material scientists now know a great deal about the features of basic structures such as a blood vessel. For example, we know that endothelial cells are more likely to be happy if seeded onto a very smooth surface and so this is how we would manufacture a tissue-engineered substitute. We also know that if endothelial cells are subjected to flow they will produce a factor known as VEGF, which promotes blood vessel formation, and so they may be cultured in a flow chamber. The tough connective tissue on the outside of the vessel, however, requires nanoscale ridges for differentiating fibroblasts to ‘hang on’ to. By providing these biomimetic nanoscale features, successful tissue engineering becomes a step closer.
Cells exist in a nanoscale environment, and I believe that it is only by understanding and replicating the nanoscale features of their environment that we will be able to engineer very complex tissues, such as the solid organs. It may be a long way off, but there is a chance that new technologies such as those developed by Anthony Atala could solve the growing crisis in organ transplantation. The use of nanotechnology in engineering complex tissues is a topic I have recently reviewed for Bone and Tissue Regeneration Insights, if you would like to know more you can read it now for free (http://bit.ly/1wmaxDb )3.
Schematic illustrating the typical stages involved in Tissue Engineering. First a tissue biopsy is taken from the patient. Cells of interest are isolated or derived according to literature best practices. Once bulked up, cells can be seeded onto a biomimetically-designed scaffold and cultured in a bioreactor designed to mimic the in vivo environment. The cell populated scaffold can then be grafted onto tissues of interest in the patient where they can help repair or augment organ function.
- Department of Health and Human Services. U.S. Government Information on Organ and Tissue Donation and Transplantation. (2014). at <http://www.organdonor.gov/>
- TEDMED. Growing new organs. (2009). at
- Cassidy, J. W. Nanotechnology in the Regeneration of Complex Tissues. Bone Tissue Regen. Insights 25 (2014). doi:10.4137/BTRI.S12331 http://bit.ly/1wmaxDb