Biotechnology

Biology

Stem cell

Cell biology

Immunology

Bone marrow

Genetics

Medicine

Major histocompatibility complex

Cell

Immune system

Pathology

Mesenchymal stem cell

In vivo

Proceedings of the National Academy of Sciences

Significance Mesenchymal stem cell (MSC) therapies have shown strong preclinical promise, particularly in ameliorating diseases of immune dysregulation. However, these results have largely failed to demonstrate efficacy in clinical settings, likely due to large dosages necessitated by the short residence time of infused cells, suboptimal cell phenotype, and immune rejection. We demonstrate that a microfluidic-based biomaterial encapsulation approach can increase in vivo residence time after intravenous (i.v.) delivery by more than an order of magnitude. Encapsulated cells up-regulated immunomodulatory genes upon exposure to inflammatory cytokines and promoted engraftment of major histocompatibility complex (MHC)-mismatched donor cells in a bone marrow transplant model. The ability to retain i.v. infused MSCs for longer durations may be broadly applicable toward improving MSC therapies.

Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation