Scientists grow human kidneys inside pigs using stem cells

“This study demonstrates proof-of-principle of the possibility of producing a humanized organ in organogenesis-disabled pigs, opening an exciting avenue for regenerative medicine and an artificial window for studying human kidney development, Lai added.

The way to grow human kidneys inside pigs

In the past, scientists have used a similar process to produce human tissue and muscles inside pigs. However, they couldn’t grow an entire organ because successfully incorporating human stem cells with pig cells is very tricky.  

For instance, pig cells tend to be more successful or dominant in such embryos because they multiply more rapidly than human cells. This competition can make it challenging for the human cells to survive and develop within the pig embryo.

Also, human and pig cells require different nutrients, environmental conditions, or signaling molecules to grow. The differences in their physiological needs further hinder the successful integration of human stem cells into pig embryos, according to the researchers.

Lai and his colleagues employed three techniques to overcome these challenges. First, they used CRISPR to eliminate two genes in pig cells that are required for pig kidney development. This ensured the growth of only human kidneys from human cells in the embryo.

Second, they engineered and used human pluripotent stem cells in the chimeric embryo. These cells can renew, grow, and divide into any type of human cells. The researchers turned them into early human embryonic cells.

Third, they created an optimized environment for the embryo to accommodate the distinct needs of both human and pig cells. This environment ensured that each cell could receive the nutrients and molecules best suited for their growth.

They used these techniques to create 1,820 chimeric embryos and then transferred those into 13 surrogate pig mothers. When they examined five embryos after 28 days, they found that they had grown into mesonephros, early-stage human kidneys with tubules and cell growths forming the ureter.

Human kidneys from pigs can reduce organ shortage 

There are over 104,000 people listed on the national transplant waiting list in the US. This number could be in millions across the globe, but what’s more unfortunate is that many such individuals die waiting.

There is a significant gap between organ donors and people who need organs. The technique proposed by the researchers has the potential to reduce this gap. However, there is some time before it is ready to work toward that goal.

When asked if the kidneys grown inside pigs were also tested in humans, Lai replied, “We did not test its functions in humans because the chimeric kidney we achieved is an early stage of kidney development and not functionally mature.” 

He suggests that achieving a fully functional humanized organ inside pigs could take years. The current research is a significant but first breakthrough toward that goal. 

He added, “Our study demonstrates proof-of-principle of the possibility of generating a humanized organ in organogenesis-disabled pigs, opening an exciting avenue for regenerative medicine and an artificial window for studying human kidney development.” 

The researchers believe that in the future, this process can also emerge as a new approach to studying human organ development and developmental disorders such as autism, ADHD, and cerebral palsy. 

They will now try to improve their method for achieving mature kidney growth. Also, using the same technique, they plan to produce other human organ primordia in pig embryos, including the heart and pancreas. 

The study is published in the journal Cell Stem Cell.

Study abstract:

Heterologous organ transplantation is an effective way of replacing organ function but is limited by severe organ shortage. Although generating human organs in other large mammals through embryo complementation would be a groundbreaking solution, it faces many challenges, especially the poor integration of human cells into the recipient tissues. To produce human cells with superior intra-niche competitiveness, we combined optimized pluripotent stem cell culture conditions with the inducible overexpression of two pro-survival genes (MYCN and BCL2). The resulting cells had substantially enhanced viability in the xeno-environment of interspecies chimeric blastocyst and successfully formed organized human-pig chimeric middle-stage kidney (mesonephros) structures up to embryonic day 28 inside nephric-defective pig embryos lacking SIX1 and SALL1.