Engineered whole organs and complex tissues

   There are many people who suffer from conditions that could be eased or even cured through the replacing of an organ. Typically this is done through an organ transplant from on individual to another, but unfortunately there is a limited number of available organs, a limited amount of time said organs are viable, and the number of people in need of organ transplant continues to grow while the number of available organs has not grown to match this need.

   Research is being conducted using the extracellular matrix of organs and tissues to help generate (or in some cases regenerate) those organs and tissues. The idea behind this is that in this extracellular matrix are certain biological factors that promote the growth of new cells, while limiting the immune response of the recipient. The immune response to a transplanted organ or tissue is due to the fact that the cells of the cells are foreign to the new host, and the immune system recognizes this and begins to attack the transplanted item. With whole organ or tissue transplants these patients are required to be on immunosuppressants for the rest of their lives to keep their body from rejecting the organ. With the new advances in this matrix scaffold the immune response to the “new” organ is minimized because the matrix is acellular (meaning that it has been decellularized). This is done through many different methods, but must be done in such a way as to not damage or remove those factors that are necessary for new cells to repopulate the matrix. The matrix is either manufactured in a lab, which is actually quite hard to accomplish, or it is taken form a preexisting organ, either from the patient or from a donor and decellularized. Once the organ has been decellularized it is repopulated by the patient’s own cells either in an external bioreactor or within the patient, using the patient as his/her own bioreactor. Depending on the organ or tissue needing to be replaced the organ in question can either be grown in place or grown somewhere else in the body and moved to the proper location after sufficient repopulation has occurred.

   The use of preexisting organ matrices seems to be an excellent way to retain the three-dimensional structure of the organ, giving the new cells a scaffold that is already in the correct shape with the necessary biomolecular cues to stimulate differentiation. Another advantage to using an existing organ is that once decellularized it still maintains the vascular network, which helps in the repopulation of the scaffold, and once the “new” organ has begun to grow assists in getting adequate blood supply to the tissue. There is a necessity for the advancement of technology that is used in external bioreactors, both in terms of sterility and disposable parts.

   The use of stem cells in such procedures has been shown to be useful, but the area that they are harvested from is organ dependent, and the use of embryonic stem cells creates some ethical issues. There is still a lot of research that needs to be done, but progress has been made and continues to move forward.

   There has already been some success with this type of procedure in both animals and in humans, but clinical trials still need to take place to sufficiently prove the concepts and determine the ethical limitations of such procedures.

   This article interested me because last week I had a guest lecturer in one of my other classes who was involved in a company called Organ Transplant Systems which was involved in building a system that allowed organs for transplant to remain viable for longer amounts of time. The technology involved in creating organs and tissue would help those people who have the means to pay for such a procedure who are not in severe organ failure. Over time such technology would hopefully reduce the number of people on transplant list and save lives.

http://www.sciencedirect.com.lib-ezproxy.tamu.edu:2048/science/article/pii/S0140673612600737