Beijing, September 16, 2023 -* In a groundbreaking scientific achievement, researchers have successfully grown early-stage human kidneys inside genetically modified pig embryos, marking the first instance of human organ development within another animal. Published in the journal Cell Stem Cell (https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00286-2) , this pioneering research could ultimately address the severe shortage of human organs available for transplantation.
This remarkable advancement involves the insertion of human stem cells into pig embryos that have been genetically altered to disable specific genes responsible for kidney development. When these modified pig embryos are implanted into surrogate pig mothers, they rapidly develop humanized kidneys within approximately 28 days. This breakthrough is a significant leap forward in the field of regenerative medicine.
Liangxue Lai, senior study author and principal investigator at the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, and Wuyi University, explained, “Rat organs have been produced in mice, and mouse organs have been produced in rats, but previous attempts to grow human organs in pigs have not succeeded.” However, this new approach significantly enhances the integration of human cells into recipient tissues, allowing the growth of human organs in pigs.
Human kidneys, vital for filtering blood and removing waste and excess water via urine, are among the most commonly transplanted organs. The demand for kidneys far surpasses the supply, resulting in lengthy waiting lists for patients in need. For instance, in the United States in 2020, approximately 100,000 people awaited kidney transplants, with only 23,000 receiving one.
The research team’s strategy involves incorporating human-induced pluripotent stem cells (iPSCs) into the embryos of other mammals, creating “chimeric” embryos capable of developing human organs. Pigs were chosen as ideal candidates due to the similarity of their organs and embryonic development to those of humans. However, the challenge lay in overcoming the competitive nature of pig cells, which differ in nutritional and chemical requirements from human cells.
To address these challenges, the researchers used CRISPR technology to disable two genes necessary for pig embryonic kidney development, providing a niche for human iPSCs to thrive. Additionally, they manipulated human iPSCs to match the developmental stage of pig cells, ensuring successful integration.
Of the 1,820 chimeric embryos implanted into 13 surrogate pig mothers, five contained early-stage humanized kidneys composed of 50% to 60% human cells. These kidneys exhibited structural normality for their stage of development and featured cells that would eventually form ureters, connecting the kidneys to the bladder.
Importantly, the study confirmed that human cells remained primarily within the kidneys and did not infiltrate other tissues in the embryos, addressing potential ethical concerns.
Despite this remarkable progress, significant challenges remain before this technology can be applied to human organ transplantation. Immune rejection remains a crucial issue, as the humanized kidneys still contain pig-derived cells. Moreover, the efficiency of the process requires improvement, as a notable number of pig embryos degenerated during the study.
Nevertheless, this pioneering research offers hope for the future of organ transplantation and a potential solution to the organ shortage crisis. In the interim, it promises to deepen our understanding of human organ development and developmental diseases, providing valuable insights for medical research and treatments.
Miguel Esteban, study co-author and principal investigator at the Guangzhou Institutes of Biomedicine and Health, emphasized the broader significance of this research, stating, “Before we get to that late state of making organs that can be on the shelf for clinical practice, this method provides a window for studying human development.” It allows for the tracing and manipulation of human cells for the study of diseases and cell lineage formation.
– In a 1st, scientists grow human kidneys inside developing pig embryos | Live Science
– World’s first human-like kidneys in grown pigs – INDIA New England News
