TY - JOUR
T1 - Encapsulation of factor IX-engineered mesenchymal stem cells in fibrinogen-alginate microcapsules enhances their viability and transgene secretion
AU - Sayyar, Bahareh
AU - Dodd, Megan
AU - Wen, Jianping
AU - Ma, Shirley
AU - Marquez-Curtis, Leah
AU - Janowska-Wieczorek, Anna
AU - Hortelano, Gonzalo
N1 - Funding Information:
This study was funded in part by a grant from Canadian Blood Services Research and Development to G.H. and A.J.W. and from NSERC CREATE grant.
PY - 2012/12
Y1 - 2012/12
N2 - Cell microencapsulation holds significant promise as a strategy for cellular therapies; however, inadequate survival and functionality of the enclosed cells limit its application in hemophilia treatment. Here, we evaluated the use of alginatebased microcapsules to enhance the viability and transgene secretion of human cord blood-derived mesenchymal stem cells in three-dimensional cultures. Given the positive effects of extracellular matrix molecules on mesenchymal stem cell growth, we tested whether fibrinogen-supplemented alginate microcapsules can improve the efficiency of encapsulated factor IX-engineered mesenchymal stem cells as a treatment of hemophilia B. We found that fibrinogen-supplemented alginate microcapsules (a) significantly enhanced the viability and proliferation of factor IX-engineered mesenchymal stem cells and (b) increased factor IX secretion by mesenchymal stem cells compared to mesenchymal stem cells in nonsupplemented microcapsules. Moreover, we observed the osteogenic, but not chondrogenic or adipogenic, differentiation capability of factor IX-engineered cord blood mesenchymal stem cells and their efficient factor IX secretion while encapsulated in fibrinogen-supplemented alginate microcapsules. Thus, the use of engineered mesenchymal stem cells encapsulated in fibrinogen-modified microcapsules may have potential application in the treatment of hemophilia or other protein deficiency diseases.
AB - Cell microencapsulation holds significant promise as a strategy for cellular therapies; however, inadequate survival and functionality of the enclosed cells limit its application in hemophilia treatment. Here, we evaluated the use of alginatebased microcapsules to enhance the viability and transgene secretion of human cord blood-derived mesenchymal stem cells in three-dimensional cultures. Given the positive effects of extracellular matrix molecules on mesenchymal stem cell growth, we tested whether fibrinogen-supplemented alginate microcapsules can improve the efficiency of encapsulated factor IX-engineered mesenchymal stem cells as a treatment of hemophilia B. We found that fibrinogen-supplemented alginate microcapsules (a) significantly enhanced the viability and proliferation of factor IX-engineered mesenchymal stem cells and (b) increased factor IX secretion by mesenchymal stem cells compared to mesenchymal stem cells in nonsupplemented microcapsules. Moreover, we observed the osteogenic, but not chondrogenic or adipogenic, differentiation capability of factor IX-engineered cord blood mesenchymal stem cells and their efficient factor IX secretion while encapsulated in fibrinogen-supplemented alginate microcapsules. Thus, the use of engineered mesenchymal stem cells encapsulated in fibrinogen-modified microcapsules may have potential application in the treatment of hemophilia or other protein deficiency diseases.
KW - Alginate
KW - Cell encapsulation
KW - Fibrinogen
KW - Hemophilia
KW - Mesenchymal stem cells
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U2 - 10.1177/2041731412462018
DO - 10.1177/2041731412462018
M3 - Article
AN - SCOPUS:84889012204
SN - 2041-7314
VL - 3
SP - 1
EP - 12
JO - Journal of Tissue Engineering
JF - Journal of Tissue Engineering
IS - 1
ER -