A Pioneer: Human-Pig Chimera Successfully Grows Humanized Kidneys

Authored by Arin Faruque

Art by Ngoc Truong

There are currently over 100,000 patients on the national organ transplant waitlist, and tragically, 17 of these patients lose their lives each day [1]. Obtaining an organ for transplantation is a significant challenge, compounded by the risk of organ rejection. However, a team of biologists at the Guangzhou Institute of Biomedicine and Health has developed an innovative approach to address this issue. Researchers have explored an alternative source for organ transplants by employing genetic engineering at the embryonic level, achieving a groundbreaking milestone in growing a human organ within another species.

The researchers looked to pigs as their chimeric organisms because of their short reproductive times and their genomes can be easily manipulated. Chimeric organisms are those organisms that  contain cells from more than one source. Specifically, human-animal chimera are used to test disease treatments and, as done in this study, can be viable sources to grow human organs. To accomplish this, the researchers utilized CRISPR gene editing to cut out two genes required for kidney growth in pig embryos. They then formed pluripotent stem cells, which are precursor cells able to mature various cell types, that resemble early human embryonic cells to inject into the pig embryo. After adjusting lab conditions to provide nutrients and signals to satisfy both the pig and human cells, the growing embryo was inserted into the surrogate pig for 28 days. Remarkably, the researchers observed that the developing kidneys exhibited normal human functionality and stable tubule formation [2].

In their approach, the researchers sought to improve methods used in previous attempts at growing organs. First, they believed that the human stem cells used were often too weak to keep up with the local pig cells. Cells in an embryo compete with each other to fulfill their tasks and those too slow often end up committing apoptosis. This led researchers to genetically modify the human stem cells to increase their activity, allowing them to survive alongside the pig cells. Furthermore, researchers found that the human cells were often developing faster than the pig cells. The researchers responded to this by growing the stem cells together in a culture medium with the nutrients needed to grow microorganisms. This resulted in the synchronization of the pig and human cells in their developmental stages.

These results have far-reaching implications in medicine, specifically in avoiding organ rejection after transplant. Organ rejection occurs when a transplant recipient’s immune system interprets the transplanted organ cells as invaders and develops antibodies to attack the transplanted organ [3]. This can occur within the first few months after transplantation, described as acute rejection, or after over a year of transplantation, called chronic rejection. Thus, these chimerically grown organs that use human cells, such as the kidney of the human-pig chimera, are incredibly valuable. Since the patient’s own cells are used, there is a decreased risk of the immune system identifying the transplanted organ as an invader and attacking it. Furthermore, 87% of patients on the transplant waiting list are waiting for a kidney [4]. This underscores the importance of this scientific advancement in particular, as these humanized kidneys grown in pigs have the potential to become a more accessible, safer option for so many people currently awaiting transplant. 

While these results are promising, the researchers emphasize that there is still a long way to go. 60% of the humanized kidney cells were human, which is an improvement from previous experiments but indicates that further genetic manipulation of the embryo will be needed to produce mature kidneys with all human cells [5]. Since organs are made up of more than one cell type, more complex methods are necessary to engineer the pigs to produce all of the cell types and tissues of the kidney. 

Furthermore, there remains the  ethical concern of injecting pigs with the chimeric embryo, as its effects on the organism are still unknown. During their analysis, the scientists had found some of the human cells in the embryo’s brain and spinal cord [6]. This can be dangerous to the organism’s mental abilities and its overall development timeline.

While it is unlikely for these grown organs to be implemented in transplants any time soon, this study is a strong first step towards the possibility of organ transplants that are grown in other animals and individualized based on the patient’s own cells.

Works Cited

1. (2023, March). Organ Donation Statistics. Organ Donor. https://www.organdonor.gov/learn/organ-donation-statistics 

2. Wang, J. (2023, September 7). Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation. Cell Stem Cell. https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00286-2 

3. Roberts, J. (2023, April 18). Transplant rejection. MedlinePlus. https://medlineplus.gov/ency/article/000815.htm#:~:text=Doctors%20use%20medicines%20to%20suppress,There%20are%20some%20exceptions%2C%20though. 

4. (2023). Kidney donation and transplant. American Kidney Fund. https://www.kidneyfund.org/kidney-donation-and-transplant 

5. Hunt, K. (2023, September 7). Scientists take ‘pioneering steps’ toward growing human kidneys in pigs. CNN.https://www.cnn.com/2023/09/07/health/growing-human-kidneys-in-pigs-scn/index.html#:~:text=The%20researchers%20involved%20said%20it's,humanized%20organ%20inside%20another%20species.&text=The%20embryos%2C%20when%20implanted%20in,development%2C%20according%20to%20the%20study. 

6. Leslie, M. (2023, September 7). Early-stage human kidneys grown in pigs for first time. Science. https://www.science.org/content/article/early-stage-human-kidneys-grown-pigs-first-time#:~:text=Researchers%20have%20coaxed%20human%20stem,people%20on%20waitlists%20for%20transplants