Encapsulation enhances stromal cell survival for safe neonatal therapy: a pilot study

Mesenchymal stromal cells (MSCs) have demonstrated therapeutic benefit in preclinical models of necrotizing enterocolitis (NEC), yet clinical translation remains limited by concerns about immune clearance and tumorigenic risk. Encapsulation strategies offer a potential solution by limiting systemic exposure while preserving efficacy. We hypothesized that encapsulation of MSCs would improve cell survival and maintain cell identity in this proof-of-concept study.

Luciferase-expressing MSCs were generated via lentiviral transduction and validated for luminescence. Mice received MSCs either intraperitoneally (n=4) or encapsulated in the surgically implanted thread-reinforced encapsulation device (THRED) (n=4). Bioluminescence imaging tracked viability over 8 days. Viability and identity of extracted cells were assessed by flow cytometry and stromal cell marker analysis.

The bioluminescent signal declined in both groups, but MSCs delivered in the THRED retained significantly greater viability on day 4 (p=0.0286) and day 8 (p=0.0286). Cells extracted from the device remained viable (p=0.0286) and maintained stromal cell marker expression matching non-implanted controls (n=4). Flow cytometry demonstrated the viability of explanted cells, as well as preserved identity based on cell surface markers.

Encapsulation within the THRED preserves MSC viability and identity in vivo. This approach provides a clinically practical method to deliver MSC therapy during initial NEC surgery or drain placement with retrieval at a later procedure. This serves as a proof-of-concept and offers a feasible solution to current barriers in neonatal MSC therapy.