Understanding Transplantation

 

“Transplantation” in the medical field is defined as “the process of taking living tissue such as stem cells or organs and implanting them in another part of the body or in another body”.

The examples of transplantation of “cells” include ordinary blood transfusion and stem cell transplantation often used to treat blood cancers such as leukemia and lymphomas.

This blog deals with the intricacies of the organ transplantation and was inspired by a recent article published in the New England Journal of Medicine in December 2021. The authors reviewed the state of art in organ transplantation and wondered if the factories manufacturing beating hearts and inflating and deflating lungs were around the corner?

The stem cells (parent cells) that have the capacity to make a variety of tissues in our bodies, have successfully been coaxed to grow in the test tubes and petri dishes to grow into sheet of cells to resemble skin or tubular structures that have been used as replacements for blood vessels.

However, making whole organs from stem cells like the heart or the kidneys that can execute biological functions, remains impossible as of this time.

Mechanical hearts have been designed that can pump blood. We know that dialysis machines can work as kidneys to filter the blood and keep one alive. But clearly these mechanical devices have their limitations.

The next best option is to transplant live organs from donors. The first organ transplantation of a kidney from a deceased person to a living human being was done in 1954. The major problem with donated organs is their rejection by the recipient’s body. Since the organs donated by other persons are “foreign” and not “self”, the body’s immune system reacts and tries to reject them. To keep the transplanted organs functioning and prevent rejection, one needs to treat the recipients with anti-rejection medications to suppress the immune system for the rest of their lives.

Such human-to-human transplantation is now commonplace. Organs such as heart and lungs, harvested from recently deceased persons, or liver and kidney both from deceased and living donors are routinely transplanted every day in major medical centers across the world.

However, there aren’t enough donated organs to meet the increasing need. This has given a push to research in the field of “xenotransplantation”, i.e. transplantation of organs across species such as a pig kidney being transplanted into humans.

The challenges of xenotransplantation include technical difficulties, higher rate of rejection and possible transmission of diseases called zoonosis, from animals to human beings.

The issue of animals being used for medical research has raised societal concerns. The large research centers with animal laboratories follow the rules and regulations that are meant to protect animal welfare. Many drugs and cosmetics are now developed without first being tested on animals. However, for more complex biological functions such as organ transplantation, animals will continue to be used until there are reliable alternatives.

In terms of size, the organs of a pig are approximately of the same size as those of a human. Hence, pigs have been the source of xenotransplantation research. As stated earlier, the major issue with organs transplantation is “rejection”.

Lot of progress has been made in understanding the science behind rejection. For example, now we have identified the proteins on the cells of pig’s kidneys that generate the rejection response. We have also identified the genes that help make those particular proteins. So, if we edit out certain genes from the DNA of the pig’s egg cell, we can make the pig’s kidney more acceptable to the human immune system.  This process is now doable by using “gene editing” tool such as “Crisper”.

Taking that a step further, it is now possible that in addition to knocking out the specific genes, human genes can be inserted into the egg cell so that the piglets that are born, have organs that are molecularly and genetically closer to the human organs.

When such human-like organs, for example a kidney is transplanted in humans, it is less likely to be rejected by the immune system of the person. The authors of this article show that such experiments have already been done successfully.

There are major concerns about “gene editing” and inserting human DNA in animals. The ethics, rules and regulations of such scientific work is monitored by international organizations such as International Commission on the Clinical Use of Human Germline Genome Editing.

It is hoped that this trans-species genetic engineering, called “exogenesis” along with our better understanding of the immune system and advances in gene editing, will one day provide ample supply of almost human-like tissues and organs to cure genetic, degenerative, and other such diseases. That day is not around the corner but we on our way to get there.