Advances in Tissue Engineering may Overcome Difficulties in Transplantation

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Highlights:

• The development of tissues in the laboratory could solve the problem of tissue availability for transplantation
• Scientists have found it difficult to develop tiny blood vessels called capillaries to nourish such tissues
• A new method suggested and tested by scientists could possibly overcome this problem

Bioengineers may be able to develop tissues with capillaries in the near future that could solve the problems associated with transplantation. A study indicating the same was published in the Biomaterials Science.

Organ transplantation saves several lives. During the surgical procedure, a tissue or an organ is obtained from a cadaver or sometimes, from another living person, as in kidney transplantation, which is then introduced into the recipient. Unfortunately, donor tissues are not always available. In addition, quite often, the transplanted organ gets rejected, further adding to the woes of the patient.

‘Scientists have found methods through which growth of capillaries in tissues may be possible, thereby providing hope for the development of tissues for transplantation.’

Scientists have tried to produce tissues in the laboratory to overcome the current difficulties associated with transplantation. The availability of such tissues will ensure an adequate supply to those who need them. Since the tissues will be made compatible with the patient's body, they will also avoid the problem of rejection. A branch of medicine referred to as tissue engineering or regenerative medicine uses stem cells to produce the tissues. The stem cells are cells that can be coaxed into developing into a particular type of cells by exposing them to a specific environment.

Any tissue that is a few cells thick requires the presence of tiny blood vessels called capillaries to provide nutrition and oxygen to the cells, and to remove carbon dioxide and waste products out of them. Capillaries arise from small arteries called arterioles, form a network within tissues and drain into small veins called venules. Therefore, tissue that is engineered in the laboratory requires the presence of capillaries, without which they cannot survive.

The capillaries are very thin walled, and contain a single layer of cells called the endothelial cells. This is in contrast to the arteries and the veins, which also contain a muscle layer surrounding the endothelial layer; the muscle layer is thicker in the arteries as compared to the veins. The muscle layer is surrounded by another layer consisting mainly of collagen.

When capillaries develop, they undergo a process called tubulogenesis, in which they assume the tubular shape of a blood vessel. The cells develop vacuoles that join together, leading to the formation of a tubular network through which blood can pass. This process is difficult to replicate in the laboratory.

Through their experiments, scientists found that it may now be possible to produce capillaries in the laboratory.

• They used induced pluripotent stem cells (iPSCs) to produce the endothelial cells of the capillaries. iPSCs can be produced from any adult, and are therefore specific for the patient. This could probably solve the problem of tissue rejection.
• They modified the cells to produce two types of fluorescent proteins, one in the nucleus and the other throughout the cell. With the help of these, they could study the cells under the microscope and monitor the changes going on in the cells.
• The cells were then mixed with fibrin, which is a natural medium, with or without another type of cell called the mesenchymal stem cells. They were incubated for a week. This procedure resulted in good tubulogenesis, irrespective of the presence or absence of the mesenchymal cells.
• Tubulogenesis was more difficult when the cells were incubated in a semisynthetic medium called gelatin methacrylate. This difficulty was overcome by the addition of mesenchymal stem cells. This finding is important since gelatin methacrylate has a great potential to be used for tissue engineering.

The development of tissues with good vascular or blood supply that can be used for transplantation will require more research but is progressing in the right direction. The scientists suggest some more immediate uses of vascularized tissues. The tissues can be used for drug testing. In the initial phases of research on a new drug, the drug is tested on cells grown in the laboratory to see how they react at a molecular level. Testing of the drug on a tissue with blood vessels will provide a more realistic medium, which will be similar to a living tissue in the body.

Moreover, the tissues, when constructed from the cells of a particular patient, can be used to test the best treatment option for that patient. Thus, the patient can be offered only the treatment that is more likely to work and cause the least side effects and be saved from the anguish, side effects and cost of treatments associated with a trial-and-error approach to the treatment of conditions like cancer.

Reference:

1. Calderon GA et al. Tubulogenesis of co-cultured human iPS-derived endothelial cells and human mesenchymal stem cells in fibrin and gelatin methacrylate gels. Biomater. Sci., (2017), Advance Article. DOI: 10.1039/C7BM00223H

Source: Medindia

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