TY - JOUR
T1 - Fibronectin-Alginate microcapsules improve cell viability and protein secretion of encapsulated Factor IX-engineered human mesenchymal stromal cells
AU - Sayyar, Bahareh
AU - Dodd, Megan
AU - Marquez-Curtis, Leah
AU - Janowska-Wieczorek, Anna
AU - Hortelano, Gonzalo
N1 - Publisher Copyright:
Copyright © 2013 Informa Healthcare USA, Inc.
PY - 2015
Y1 - 2015
N2 - Continuous delivery of proteins by engineered cells encapsulated in biocompatible polymeric microcapsules is of considerable therapeutic potential. However, this technology has not lived up to expectations due to inadequate cell - matrix interactions and subsequent cell death. In this study we hypothesize that the presence of fibronectin in an alginate matrix may enhance the viability and functionality of encapsulated human cord blood-derived mesenchymal stromal cells (MSCs) expressing the human Factor IX (FIX) gene. MSCs were encapsulated in alginate-PLL microcapsules containing 10, 100, or 500 μ g/ml fibronectin to ameliorate cell survival. MSCs in microcapsules with 100 and 500 μ g/ml fibronectin demonstrated improved cell viability and proliferation and higher FIX secretion compared to MSCs in non-supplemented microcapsules. In contrast, 10 μ g/ml fibronectin did not significantly affect the viability and protein secretion from the encapsulated cells. Differentiation studies demonstrated osteogenic (but not chondrogenic or adipogenic) differentiation capability and efficient FIX secretion of the enclosed MSCs in the fibronectin-alginate suspension culture. Thus, the use of recombinant MSCs encapsulated in fibronectin-alginate microcapsules in basal or osteogenic cultures may be of practical use in the treatment of hemophilia B.
AB - Continuous delivery of proteins by engineered cells encapsulated in biocompatible polymeric microcapsules is of considerable therapeutic potential. However, this technology has not lived up to expectations due to inadequate cell - matrix interactions and subsequent cell death. In this study we hypothesize that the presence of fibronectin in an alginate matrix may enhance the viability and functionality of encapsulated human cord blood-derived mesenchymal stromal cells (MSCs) expressing the human Factor IX (FIX) gene. MSCs were encapsulated in alginate-PLL microcapsules containing 10, 100, or 500 μ g/ml fibronectin to ameliorate cell survival. MSCs in microcapsules with 100 and 500 μ g/ml fibronectin demonstrated improved cell viability and proliferation and higher FIX secretion compared to MSCs in non-supplemented microcapsules. In contrast, 10 μ g/ml fibronectin did not significantly affect the viability and protein secretion from the encapsulated cells. Differentiation studies demonstrated osteogenic (but not chondrogenic or adipogenic) differentiation capability and efficient FIX secretion of the enclosed MSCs in the fibronectin-alginate suspension culture. Thus, the use of recombinant MSCs encapsulated in fibronectin-alginate microcapsules in basal or osteogenic cultures may be of practical use in the treatment of hemophilia B.
KW - Alginate
KW - Bioactivity
KW - Cell encapsulation
KW - Factor IX
KW - Fibronectin
KW - Hemophilia B
KW - Mesenchymal stromal cells
UR - http://www.scopus.com/inward/record.url?scp=84946402797&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946402797&partnerID=8YFLogxK
U2 - 10.3109/21691401.2014.885446
DO - 10.3109/21691401.2014.885446
M3 - Article
C2 - 24564349
AN - SCOPUS:84946402797
SN - 2169-1401
VL - 43
SP - 318
EP - 327
JO - Artificial Cells, Nanomedicine and Biotechnology
JF - Artificial Cells, Nanomedicine and Biotechnology
IS - 5
ER -