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Synthetic Stem Cells Regenerate Heart Tissue in Mice

These engineered “cells” were made from the secretions and membranes of human mesenchymal stem cells.

Jun 1, 2017
Diana Kwon

STEM “CELL” SYNTHESIS: To create synthetic mesenchymal stem cells (synMSCs), the researchers start with human bone marrow-derived MSCs (1). They combine secretions from these cells with a biodegradable polymer, poly(lactic-co-glycolic acid) or PLGA, creating microparticles (2). The microparticles are then encased in cell membranes derived from human MSCs (3) to allow the synMSCs to anchor to tissues and gradually release secreted factors, mimicking real MSCs (4).© GEORGE RETSECK. REDRAWN FROM CIRC RES, doi:10.1161/CIRCRESAHA.116.310374, 2017, WITH PERMISSION

Mesenchymal stem cells (MSCs) are typically derived from adult bone marrow and fat tissue and are currently being tested in hundreds of clinical trials. They secrete proteins and other molecules that, when released to tissues, can promote regeneration, acting “like a pharmacy that provides drugs for tissues to heal,” says Ke Cheng, a biomedical engineer at North Carolina State University and the University of North Carolina at Chapel Hill.

One limitation is that these cells need to be carefully frozen to keep them alive in storage, then defrosted, expanded, and gently maintained until used. “This process is tedious and sometimes can affect the potency of the cell,” Cheng says. He also points out that some cells will inevitably die during handling, and injecting dying or dead cells into a patient can activate an inflammatory response.

To address these shortcomings, Cheng and colleagues engineered synthetic MSCs (synMSCs) built from human MSC secretions packaged in a biodegradable microparticle that was then coated with MSC cell membranes. These artificial cells withstood harsh cryopreservation and lyophilization (freeze-drying) without losing any of their properties. And when the researchers injected the membrane-bound particles into the hearts of a mouse model of myocardial infarction, the “cells” were able to promote regeneration to roughly the same degree as human MSCs.

SynMSCs could one day lead to off-the-shelf stem cell therapies, Cheng says—something that is very difficult to achieve with human- or animal-derived stem cells due to their fragility.

“I think it’s a clever idea, and it has potential,” says Joshua Hare, who develops cardiac cell therapies at the University of Miami Miller School of Medicine. “This is really a proof-of-principle demonstration, and there’s a lot they have to do to get it to the level where it could actually be usefully applied.” (Circ Res, doi:10.1161/CIRCRESAHA.116.310374, 2017) 

 

CELL TYPE MODE OF DELIVERY VIABILITY APPROXIMATE SIZE TESTED IN
Synthetic mesenchymal stem cells
 
Must be injected directly into site of action (e.g., heart) At least one week at room temperature 20 μm Mice
Mesenchymal stem cells derived from humans or other animals Can be injected into blood vessels, because they will migrate to the site of injury Around 24 hours at room temperature 20 μm Humans, in multiple clinical trials

 

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