Assessment of mesenchymal stem cell effect on foreign body response induced by intraperitoneally implanted alginate spheres

Abstract Foreign body response to implanted hydrogels and consequently fibrotic overgrowth on implanted spheres will decrease in vivo performance of these biomaterials. Considering the previous reports related to the immune‐privileged properties of mesenchymal stem cells (MSCs), we hypothesized that encapsulated human placenta‐derived MSCs (HP‐MSCs) will mitigate the foreign body response against alginate hydrogels. The HP‐MSC‐laden alginate hydrogel was cross‐linked with a CaCl₂ solution. Morphological and mechanical properties of alginate spheres were determined by scanning electron microscopy imaging, degradation, and swelling tests. The HP‐MSC‐laden alginate spheres or cell‐free spheres were implanted into the peritoneal cavity of BALB/c mice. After intraperitoneal implantation of spheres into BALB/c mice over a period of 14 days, capsules were recovered and precapsular fibrotic tissue on their surfaces was investigated. Assessment of encapsulated HP‐MSC viability using acridine orange/propidium iodide staining revealed that foreign body response against cell‐laden hydrogel results in fibrous overgrowth on spheres and consequently leads to the HP‐MSC necrosis. In spite of immunomodulatory effects of MSCs, the introduction of spheres into the body induces foreign body response that affects the viability of immuno‐isolated HP‐MSCs during 14‐day posttransplant period. The presence of HP‐MSCs within alginate hydrogel could not reduce the fibrotic overgrowth on spheres compared with cell‐free spheres. Therefore, there is an essential need for hydrogels that mitigate the foreign body response as a key challenge in the development of tissue engineering and drug delivery technologies.