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The Prospect of Growing Human Organs in Animals as a Source of Transplants


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Posted 13 February 2019 - 10:01 PM


Farming animals is morally dubious, to say the least, but we live in a world in which most people are accepting of this practice. That doesn't make it right, and I think that this will change in the future. For now, however, anyone who finds farming animals for meat ethical should also consider it ethical to create genetically altered animals that contain either human organs or organs that can be humanized. The purpose in doing this is to provide a large supply of organs for transplantation, alleviating the present shortage of organs for that purpose. This is not the only approach, of course. Many research groups are working towards the growth of new organs from tissue samples, where the creation of blood vessel networks sufficient to support larger tissue sections is the biggest challenge. Others are investigating the use of decellularization to expand the pool of donor organs by recovering those that are damaged and would normally be discarded.

But back to sourcing organs from animals, there are a number of ways to obtain organs for transplantation in this way. The first is to use decellularization with an appropriately sized organ, and pigs are a useful species in this respect. The pig cells are stripped away, leaving the extracellular matrix and its biochemical cues. Human cells of the necessary types, derived from the transplant recipient, are introduced to repopulate the organ. This line of development is still somewhere in progress, as other species have a handful of problematic proteins in the extracellular matrix. At least one group is farming genetically engineering pigs that lack these proteins.

The other approach is noted in the research materials here, which is to create animal lineages in which human organs are growing. This may also require some additional work to remove problem proteins before an organ can be transplanted, and is further behind the decellularization and genetically engineered pigs approach. Nonetheless, it seems equally viable. It is an open question as to which of these various lines of research and development will prosper in the clinic, and when, in the years ahead. Still, I would say that farming organs is a stop-gap technology, something that will be replaced with the creation of organs from patient cells.

Researchers one step closer to growing made-to-order human kidneys

For patients with end-stage renal disease, a kidney transplant is the only hope for regaining quality of life. Yet many of these patients will never undergo transplant surgery thanks to a chronic shortage of donor kidneys. But researchers have been working on ways to grow healthy organs outside the human body. One such method, called blastocyst complementation, has already produced promising results. Researchers take blastocysts, the clusters of cells formed several days after egg fertilization, from mutant animals missing specific organs and inject them with stem cells from a normal donor, not necessarily of the same species. The stem cells then differentiate to form the entire missing organ in the resulting animal. The new organ retains the characteristics of the original stem cell donor, and can thus potentially be used in transplantation therapy.

Initial attempts by the researchers to grow rat kidneys in mice proved unsuccessful, as rat stem cells did not readily differentiate into the two main types of cells needed for kidney formation. However, when the reverse scenario was attempted, mouse stem cells efficiently differentiated inside rat blastocysts, forming the basic structures of a kidney. After being implanted into pseudo-pregnant rats, the complemented blastocysts matured into normal fetuses. Remarkably, more than two thirds of the resulting rat neonates contained a pair of kidneys derived from the mouse stem cells. Further screening showed that all of the kidneys were structurally intact, and at least half could potentially produce urine. "Our findings confirm that interspecific blastocyst complementation is a viable method for kidney generation. In the future, this approach could be used to generate human stem cell-derived organs in livestock, potentially extending the lifespan and improving the quality of life of millions of people worldwide."

Generation of pluripotent stem cell-derived mouse kidneys in Sall1-targeted anephric rats

Regeneration of human kidneys in animal models would help combat the severe shortage of donors in transplantation therapy. Previously, we demonstrated by interspecific blastocyst complementation between mouse and rats, generation of pluripotent stem cell (PSC)-derived functional pancreas, in apancreatic Pdx1 mutant mice. We, however, were unable to obtain rat PSC-derived kidneys in anephric Sall1 mutant mice, likely due to the poor contribution of rat PSCs to the mouse metanephric mesenchyme, a nephron progenitor.

Here, conversely, we show that mouse PSCs can efficiently differentiate into the metanephric mesenchyme in rat, allowing the generation of mouse PSC-derived kidney in anephric Sall1 mutant rat. Glomerular epithelium and renal tubules in the kidneys are entirely composed of mouse PSC-derived cells expressing key functional markers. Importantly, the ureter-bladder junction is normally formed. This data provides proof-of-principle for interspecific blastocyst complementation as a viable approach for kidney generation.


View the full article at FightAging




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