Vascularization: A tissue engineering roadblock

Author: Allison Van Winkle, 08/16/10

There are currently over 100,000 people in the United States on the waiting list for an organ transplant. Between January and March of 2010, fewer than 7,000 patients received transplants. Imagine, as an alternative to donated live tissue, a tissue-engineered alternative, such as a bioartificial liver or pancreas. Tissue engineered products could substantially decrease the waiting time required for transplantation, while restoring degenerated function as effectively as a live tissue transplant.

There are many research hurdles that must be overcome prior to the development of a tissue-engineered organ replacement. Cell populations must be identified, expanded into large numbers, differentiated and/or purified to a desired type of cell. The cells must orientate into a three-dimensional environment of sufficient size, possibly using a scaffold. However, as the size of the scaffold increases it becomes more difficult to deliver nutrients and oxygen to the cells, along with the simultaneous removal of waste.

In vivo, this is accomplished through a complex network of vascularisation. In the body, cells are usually within 100 µm of a blood vessel. Currently, in tissue-engineered products, cells can be up to centimetres away from a nutrient source. The need for vascularisation to be developed in vitro is currently considered one of the main roadblocks to the clinical use of tissue-engineered devices.

There are several vascularisation approaches currently being researched. These include:

  1. Growth factors. The use of growth factors may be used to stimulate the growth of blood vessels from patient to the tissue-engineered product. However, this method has been found to have a low efficiency in clinical trials.
  2. Multiple transplantation. The tissue-engineered product is implanted into a highly vascularised area, such as muscle tissue, to encourage the growth of blood vessels. The tissue-engineered device is then transplanted to the area of interest. While feasible, this process is unlikely to translate to clinical application, due to the complex process requiring multiple steps and/or surgeries.
  3. Supply of blood vessel forming cells. The use of endothelial lineage cells in the tissue-engineered device could promote the growth of blood vessels. However, this results in a tissue-engineered product containing multiple cell types, increasing the complexity of cell culturing and product development, as product purity and consistency becomes increasingly difficult to maintain.

The supply of blood vessel forming cells seems a promising research area; however a source of many endothelial cells is required. Immediate isolation of endothelial cells from the skin is inefficient with respect to obtaining enough cells for clinical use. However, the use of mesenchymal stem cells or endothelial precursor cells as a source of blood vessel forming cells may help overcome this tissue engineering roadblock. These cells could possibly be obtained non-invasively from a patient and expanded in vitro to large, clinically relevant numbers.

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