Tissue Engineering

Fig. 1 - Cell Culturing of Cytoskeleton

The need to replace or repair damaged skin, bone, cartilage, organ and even nervous tissue is driving the biomedical discipline of tissue engineering, an expanding area of research that draws from many areas of biological and engineering expertise. Current studies are exploring tissue replacement using both cellular therapy and artificial tissue constructs.

Cell Therapies Associated With Tissue Engineering

The reconstruction of functional tissue using living cells is widely considered to hold the most promise in terms of creating effective implants that mimic the metabolic processes of their surrounding cells (Fodor, 2003). Cell therapies currently being investigated include those using mature cells and stem cells from the actual patient (autologous cells), those involving cells from other humans (allogeneic cells), and even transgenic cells from other species (xenogeneic cells).

Cell Therapy Using Autologous Cells

The advantage of culturing and then implanting tissue from the patient’s own body is that rejection by the person’s immune system will not occur, thereby obviating the need for inconvenient and potentially hazardous immunosuppressive drugs. Some of the cell types in this category include chondrocytes, which have the ability to repair cartilage, myocytes, capable of repairing myocardial tissue, and keratinocytes, cells used to repair wounds and burn affected tissue. Other autologous cells under investigation include retinal epithelial cells, which have the potential to treat macular degeneration and Schwann cells, which can repair the myelin that coats nerve cells.

Clinical trials in this area have involved removing the desired cells from a patient, culturing them in vitro, and implanting them in another part of the body. This procedure can be fraught with difficulties such as the pain and discomfort of surgery and problems associated with culturing enough of the cells on nutrient media. Researchers need to supply cell cultures with optimum conditions of temperature, oxygenation, pH, nutrients and humidity, and monitor diffusion rates across the cell mass as it grows. If the culture does become too large and complex other methods are required to transport materials to and from the cells.

Despite these drawbacks, two procedures have gained clinical approval by the FDA. The Biotech company Genozyme supplies a therapy that repairs damaged cartilage using autologous chondrocytes and also markets ‘Epicel’, an autologous keratinocyte treatment for burns.

Cell Therapy Using Autologous and Allogeneic Stem Cells

Autologous stem cells from bone marrow have been shown to have the ability to differentiate into nerve, myocardial, liver and cartilage tissue. Such stem cells are said to be ‘multipotent’, as opposed to ‘pluripotent’ embryonic stem cells, which have even more potential to diversify. Autologous stem cell research is still in the experimental stage.

Allogeneic stem cells, including those of blood and bone marrow, have also displayed the potential to develop into various cell types, including neural cells with the potential to repair spinal injuries. Any future treatments would need to be accompanied by immunosuppressive medication, or the cells could possibly be genetically engineered to reduce tissue rejection. A similar scenario exists with embryonic stem cells, but ethical issues and the need for further research have delayed progress in this area.

Cell Therapy Using Allogeneic Cells

Mature allogeneic cells, coupled with immunosuppressive drugs such as cyclosporine, also have the potential to form tissue cultures suitable for implantation. More successful trials, as with those using autologous cells, have been in the area of connective tissue and skin repair. Two clinically approved products, 'Apligraft' (Organogenesis) and 'Dermagraft' (Smith and Nephew), are presently used to replace skin in ulcerated wounds. Both employ implants that have been constructed from cultured neonatal foreskin cells.

Cell Therapy Using Xenogeneic Cells

An interesting development in tissue engineering research has involved the use of aortic valves from pigs in the replacement of faulty valves in humans. These porcine valves are first ‘acellularised’, which involves removing their cells with the enzyme trypsin, and then used as a scaffold for the ‘reseeding’ and growth of autologous cells from a patient with faulty heart valves.

Difficulties associated with this technique include the fact that these valves are of limited durability and their functioning is often impaired by the chemical acellularising treatment they are exposed to.

Tissue Engineering Using Artificial Constructs

In addition to aortic valves from pigs, synthetic polymers such as polylactic acid, polyglycolic acid and polyglactin are being investigated as possible scaffolds for the re-seeding of human cells and subsequent implantation as replacement valves. Most of the polymers used in this situation are biodegradable, which means they can be reabsorbed by the body after they have served their purpose as a matrix for the replacement tissue.

Such artificial constructs may also serve as matrices for replacement skin, bone and cartilage tissue. Millenium Biologix, in conjunction with Biodyn and the Marshall Space Centre, is in fact conducting experiments in which synthetic bone is seeded with human bone cells. These tissue constructs are grown in space (see fig. 1), as cells grown in this 'microgravity' environment tend to grow in a similar manner to the way they grow in the human body.

The potential of these synthetic scaffolds for encapsulating implants as a means of reducing the immune response is also being examined (National Institute of Standards and Technology, 2005). Indeed, it may become possible to introduce insulin producing pancreatic cells into diabetic patients by surrounding these cells with a synthetic ‘cage’ to minimise rejection.

Tissue Engineering and the Future

Successful outcomes in the area of organ replacement research, in particular, could result in major economic and health benefits globally. Moreover, further breakthroughs in research aimed at reducing tissue rejection (including the production of transgenic animals as a source of xenografts) could help to save or prolong human life on a scale previously considered unattainable.

References

Biotissue Technologies, 2004, 'NIH Definition of Tissue Engineering', tissue-engineering.net

Fodor, W., 2003, ‘Tissue Engineering and Cell based Therapies, From the Bench to the Clinic: The Potential to Replace, Repair and Regenerate’, Reproductive Biology and endocrinology, nih.gov

Marshall Space Flight Centre, 2008, 'Cellular Biotechnology Operations Support System (CBOSS) - Expedition Three', nasa.gov

National Institute of Standards and Technology, 2005, 'ATP Focused Program: Tissue Engineering', nist.gov