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Pluripotent stem cells are the first of its kind to be created with the use of CRISPR-Cas9 gene-editing system.

First Pluripotent Stem Cells to Prevent Transplant Rejection

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Scientists at the University of California San Francisco have developed the first pluripotent stem cells which are invisible to the immune system. This study was published in the Nature Biotechnolgy on 18 February 2019.

Pluripotent stem cells are the first of its kind to be created with the use of CRISPR-Cas9 gene-editing system. These stem cells were developed in a laboratory and are said to be functionally invisible to the immune system.

The immune system is considered to be relentless. It works in a way which removes and eliminates anything it recognizes as different or alien. Thus, it protects the human body from infectious components.

When a transplant procedure is performed on a human body, the transplanted tissues, cells or organs are interpreted as dangerous by the immune system and thus results in transplant rejection. In medical terms when a rejection occurs, the patient and the donor are said to be “histocompatibility mismatched”.

Thus the need for creating gene-edited pluripotent stem cells appeared. These stem cells are universal stem cells which are more effective than stem cells tailor-made for each patient differently.

Scientists at the domain of stem cell transplants thought that the problem of rejection was solved by induced pluripotent stem cells (iPSCs). These stem cells are made from fat cells or skin as they are fully matured. They are then reprogrammed in ways which allow them to develop into multiple cells.

Scientists transplanted the iPSCs cells into the patient who originally donated the cells. It was believed that if the body would see the iPSCs transplanted cells as “self” they would not attack the cells.

Many patient’s cells proved unfavorable to reprogramming. This process is also expensive and time-consuming as making iPSCs for every patient differently is difficult. The major issues with iPSCs technology are reproductivity and quality control.

Therefore, to overcome these challenges scientists created the “universal” iPSCs which turned out to be favorable and efficient.

Tobias Deuse, MD and also the lead author of the study says, “Scientists often tout the therapeutic potential of pluripotent stem cells, which can mature into any adult tissue, but the immune system has been a major impediment to safe and effective stem cell therapies.”

Sonja Schrepfer, PhD and a senior author of the study says, “We can administer drugs that suppress immune activity and make rejection less likely. Unfortunately, these immunosuppressants leave patients more susceptible to infection and cancer.”

During the study, three genes were altered for iPSCs to avoid rejection in histocompatibility mismatched recipients. Scientists used CRISPR to remove two genes which are important for the functioning of proteins called histocompatibility complex (MHC) class I and II.

Cells that are missing the MHC proteins become a target for the immune cells known as natural killer (NK) cells. CD47, a cell surface protein works against the effects of NK cells. With this outcome, the scientists loaded the CD47 gene into a virus.

The scientists then transplanted the mouse stem cells into mismatched mice with a normal immune system and noticed that there was no rejection. The scientists further transplanted the human stem cells into the humanized mice, whose immune system was replaced with components of the human immune system. The results were the same, there was no rejection of the transplant.

With the development of these pluripotent stem cells, it is a step closer to helping people and giving rebirth to medicine.

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