Cell-matrix Interactions of Factor IX (FIX)-engineered human mesenchymal stromal cells encapsulated in RGD-alginate vs. Fibrinogen-alginate microcapsules

Abstract

The success of cell microencapsulation technology in tissue engineering and protein delivery applications depends on the viability and functionality of the encapsulated cells, which in turn are dependent upon cell/matrix interactions. In this work, we compared the viability of cord blood-derived mesenchymal stromal cells (CB MSCs), engineered to secrete factor IX (FIX) for hemophilia treatment, and encapsulated in arginine-glycine-aspartate (RGD)-alginate versus fibrinogen-alginate microcapsules. We evaluated the effect of the biomimetic matrix on cell attachment, proliferation, and secretion of FIX. Compared with nonsupplemented alginate matrix, RGD-alginate significantly enhanced the viability of the encapsulated MSCs. Further, cells in RGD-alginate displayed distinct attachment morphology, thus suggesting that RGD-alginate can potentially be used for the encapsulation of MSCs in tissue engineering applications that require enhanced cell attachment and viability. However, our data also showed that RGD-alginate microcapsules, in contrast to fibrinogen-alginate microcapsules, did not significantly improve cell proliferation of or FIX secretion by encapsulated MSCs. Our findings suggest that evidence of cell attachment alone may not accurately predict the functionality of cells in biomimetic microcapsules.

Sustained expression of coagulation factor IX by modified cord blood‐derived mesenchymal stromal cells

“…With the increased focus on biomaterials engineered to support the growth of administered cells, a number of cell scaffolds and encapsulation approaches have been developed for specific niches and tissue types . MSCs are increasingly used in conjunction with these biomaterials, which are able to promote MSC differentiation to specific lineages.…”

Cell Encapsulation Within Alginate Microcapsules: Immunological Challenges and Outlook

“…However, the viability of human mesenchymal stem cells (hMSCs) in alginate microcapsules is not optimal. We, and others, have decorated alginate with peptides or proteins that improve the cellular attachment of hMSCs on alginate (Yu et al, 2010; Sayyar et al, 2012, 2014, 2015). The addition of the amino acid residue RGD, fibrinogen or fibronectin enhanced cell viability, proliferation and/or transgene expression, as well as modulate stem cell differentiation.…”

Replacing bad (F)actors: hemophilia

“…To address these obstacles, Hortelano et al have been investigating the ability of different biomaterials to improve cord blood-derived MSC viability and FIX production after transplantation. 28 They have shown that both arginine-glycine-aspartate (RGD) and fibrinogen-coated alginate-PLL microcapsules improve cell survival over noncoated microcapsules. However, only fibrinogen-coated microcapsules improved FIX secretion.…”