Application of enucleated cells in the treatment of diseased tissues

The findings were published in the December 20, 2021 issue of the journal Nature Biomedical Engineering

Precisely targeting a drug or therapy to diseased cells and tissues can significantly improve treatment outcomes while reducing side effects

In a mouse model of acute inflammation and pancreatitis, the researchers engineered enucleated cells called "Cargocytes" with an anti-inflammatory cytokine -- a signaling protein that stimulates immune responses and reduces inflammation and related diseases , which were then systematically injected into mice, producing high levels of the bioactive therapy at the target site in the mice, and a few days later, the disease improved

"These sac cells retain most of their cellular functions, but now also have a greatly enhanced ability to carry and deliver therapeutics specifically to target tissues in a safe manner," Klemke said

The authors say the use of enucleated, modified MSCs has several advantages over methods that use whole cells as carriers

First, regulatory approval is difficult for clinical applications of broadly engineered stem cells, which also have the ability to proliferate and differentiate, due to safety concerns

Second, primary cells collected from donors for therapy have limited bioengineering and therapeutic capabilities

Third, because sac cells are incapable of transcribing new genes, the fate of sac cells is more defined and predictable after administration, eliminating the possibility that they may produce unwanted factors, differentiate into unwanted cell types, or end up in undesired Possibility of grafting onto tissue in the desired manner

"This means that what we designed in vitro to engineer in the lab will work correctly in vivo," Klemke said

Klemke said the next steps involve optimizing the ability of Cargocytes to deliver multiple different treatments to diseased tissues in the body, exploring opportunities for engineers to account for other cells, such as immune cells, and developing a similar approach to finding and destroying metastatic cancers that have spread throughout the body

Co-authors include: Huawei Wang, Christina N.

Journal Reference :

1. Huawei Wang, Christina N.