According to research led by a professor from Northeastern University, the reprogramming of human skin cells into heart valve cells will be used to transplant a pig heart valve into a rodent effectively. The research does not reprogram the skin cells to pluripotent stem cells, nor does it involve the use of a virus in the form of a vector. This approach may become a new way to successfully transplant organs in humans.
“Even though this idea works in theory, similar tissue or organ replacement procedure could be carried out as long as the intended tissue or organ cell types can be induced and seeded onto a decellularized animal (like a pig) tissue or organ, which could potentially come up with engineered, functional tissues or organs,” said Ning Wang, professor of bioengineering at Northeastern.
Wang provided the idea and led the research, which was executed by two labs led by Junwei Chen at Huazhong University of Science and Technology in China. This work is featured in the journal Bioactive Materials.
Around 30,000 Americans die each year due to the failure of the aortic valve in their heart. The latest strategy approaches, such as using bioprosthetic or mechanical valves made of metal and rubber as substitutes have limitations, particularly in patients who are in their growing stage. Wang and colleagues say that a new frontier in treatment involves using aortic valves from pigs, which have a heart structure similar to humans. “These valves can grow along with the patient,” says Wang.
The human body has no use for foreign parts and, especially, none that come from a swine. The pig heart valve will be rejected because the valve has different, incompatible cells within its lining. Wang and the team came up, with making human valve cells that make the pig heart valve compatible.
Using a combined strategy of soluble chemicals, cytokines, and substrate stiffness modulation, mouse embryonic fibroblasts and human primary adult fibroblasts are effectively transdifferentiated into induced aortic endothelial cell-like cells (iAECs) and induced valvular endothelial cell-like cells (hiVECs), respectively, without expressing pluripotency markers. These cells express VEC-specific genes, proteins, and the marker NFATC1 and function well in culture and on decellularized porcine aortic valves for 60 days post-transplantation into immune-compromised rats. Unlike iPSC-derived cells, which express pluripotency markers and form teratomas, hiVECs do not.
“Our findings show an efficient method to convert fibroblasts into iAECs and hiVECs, enabling their seeding onto decellularized aortic valves to safely produce autologous tissue-engineered aortic valves without using viruses or initial reprogramming into pluripotent stem cells. The simplest viruses and pluripotent stem cells that are problematic can cause a tumor or infections,” says Wang.
“Recent advancements in 3D-printing heart tissues, will be interesting to explore whether our protocol can be used in the future to produce and seed autologous hiVECs onto a 3D-printed aortic valve, producing a functional tissue-engineered human aortic valve,” says Wang and colleagues.
Reference: Tang P, Wei F, Qiao W, et al. Engineering aortic valves via transdifferentiating fibroblasts into valvular endothelial cells without using viruses or iPS cells. Bioact Mater. 2024;45:181-200. doi:10.1016/j.bioactmat.2024.11.018‌
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