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Gene transfer strategies in tissue engineering.

Bleiziffer O, Eriksson E, Yao F, Horch RE, Kneser U - J. Cell. Mol. Med. (2007 Mar-Apr)

Bottom Line: Techniques of molecular biology can enhance the regenerative potential of a biomaterial by co-delivery of therapeutic genes, and several different strategies have been used to achieve that goal.Possibilities for application are many-fold and have been investigated to regenerate tissues such as skin, cartilage, bone, nerve, liver, pancreas and blood vessels.This review discusses advantages and problems encountered with the different gene delivery strategies as far as they relate to tissue engineering, analyses the positive aspects of polymeric gene delivery from matrices and discusses advances and future challenges of gene transfer strategies in selected tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Plastic and Hand Surgery, University of Erlangen Medical Center, Krankenhausstrasse 12, 91054 Erlangen, Germany.

ABSTRACT
Aiming for regeneration of severed or lost parts of the body, the combined application of gene therapy and tissue engineering has received much attention by regenerative medicine. Techniques of molecular biology can enhance the regenerative potential of a biomaterial by co-delivery of therapeutic genes, and several different strategies have been used to achieve that goal. Possibilities for application are many-fold and have been investigated to regenerate tissues such as skin, cartilage, bone, nerve, liver, pancreas and blood vessels. This review discusses advantages and problems encountered with the different gene delivery strategies as far as they relate to tissue engineering, analyses the positive aspects of polymeric gene delivery from matrices and discusses advances and future challenges of gene transfer strategies in selected tissues.

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Related in: MedlinePlus

Combination of bone tissue engineering, gene therapy based on human mesenchymal stem cells (MSCs) and silk fibroin biomaterials to study the impact of viral transfection on MSC osteogenic performance. MSCs were transduced with adenovirus containing a human BMP-2 (Ad-BMP-2) gene at clinically reasonable viral concentrations and cultured for 4 weeks. Controls with non-transfected MSCs, but exposed to exogenous BMP-2 concentrations on an analogous time profile as that secreted by the Ad-BMP-2 group, were compared. Both the Ad-BMP-2 MSC group and the exogenous protein BMP-2 group strongly expressed osteopontin and bone sialoprotein. Cells secreted a matrix that underwent mineralization on the silk fibroin scaffolds, forming clusters of osseous material, as determined by micro-computed tomography. The expression of osteogenic marker proteins and alkaline phosphatase was significantly higher in the Ad-BMP-2 MSC group than in the exogenous protein BMP-2 group, and no significant differences in mineralization were observed in two of the three MSC sources tested.The results demonstrate that transfection resulted in higher levels of expression of osteogenic marker genes, no change in proliferation rate and did not impact the capacity of the cells to calcify tissues on these protein scaffolds.These findings suggest additional options to control differentiation where exogenous additions of growth factors or morphogens can be replaced with transfected MSCs. Light microscopy of construct cross sections after 2 weeks (A–F) or 4 weeks (G–L) of cultivation in osteogenic medium (B, C, E, F, H, I, K, L) or control medium (A, D, G, J). MSC were either transduced with Ad-BMP-2 (center column) or exposed to BMP-2 concentrations as secreted and measured for the Ad-BMP-2 transduced cells (right column) or cultivated in control medium (left column). Sections were stained with H&E (A–C; G–I) or with von Kossa (D–F; J–L). Bar length is 100 μm. Reprinted from [63], with permission from Elsevier.
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fig02: Combination of bone tissue engineering, gene therapy based on human mesenchymal stem cells (MSCs) and silk fibroin biomaterials to study the impact of viral transfection on MSC osteogenic performance. MSCs were transduced with adenovirus containing a human BMP-2 (Ad-BMP-2) gene at clinically reasonable viral concentrations and cultured for 4 weeks. Controls with non-transfected MSCs, but exposed to exogenous BMP-2 concentrations on an analogous time profile as that secreted by the Ad-BMP-2 group, were compared. Both the Ad-BMP-2 MSC group and the exogenous protein BMP-2 group strongly expressed osteopontin and bone sialoprotein. Cells secreted a matrix that underwent mineralization on the silk fibroin scaffolds, forming clusters of osseous material, as determined by micro-computed tomography. The expression of osteogenic marker proteins and alkaline phosphatase was significantly higher in the Ad-BMP-2 MSC group than in the exogenous protein BMP-2 group, and no significant differences in mineralization were observed in two of the three MSC sources tested.The results demonstrate that transfection resulted in higher levels of expression of osteogenic marker genes, no change in proliferation rate and did not impact the capacity of the cells to calcify tissues on these protein scaffolds.These findings suggest additional options to control differentiation where exogenous additions of growth factors or morphogens can be replaced with transfected MSCs. Light microscopy of construct cross sections after 2 weeks (A–F) or 4 weeks (G–L) of cultivation in osteogenic medium (B, C, E, F, H, I, K, L) or control medium (A, D, G, J). MSC were either transduced with Ad-BMP-2 (center column) or exposed to BMP-2 concentrations as secreted and measured for the Ad-BMP-2 transduced cells (right column) or cultivated in control medium (left column). Sections were stained with H&E (A–C; G–I) or with von Kossa (D–F; J–L). Bar length is 100 μm. Reprinted from [63], with permission from Elsevier.

Mentions: Meinel et al. transduced MSCs with adenovirus containing a human BMP-2 gene at clinically reasonable viral concentrations and cultured for 4 weeks. Cells secreted a matrix that underwent mineralization on the silk fibroin scaffolds, forming clusters of osseous material and the expression of osteogenic marker proteins, and alkaline phosphates was significantly higher in the Ad-BMP-2 MSC group than in the control group that had received exogenous protein BMP-2. The results demonstrate that transfection resulted in higher levels of expression of osteogenic marker genes, no change in proliferation rate and did not impact the capacity of the cells to calcify tissues on these protein scaffolds, suggesting that exogenous addition of growth factors or morphogens can be replaced with transfected MSCs [63, Fig. 2, printed with permission from Elsevier].


Gene transfer strategies in tissue engineering.

Bleiziffer O, Eriksson E, Yao F, Horch RE, Kneser U - J. Cell. Mol. Med. (2007 Mar-Apr)

Combination of bone tissue engineering, gene therapy based on human mesenchymal stem cells (MSCs) and silk fibroin biomaterials to study the impact of viral transfection on MSC osteogenic performance. MSCs were transduced with adenovirus containing a human BMP-2 (Ad-BMP-2) gene at clinically reasonable viral concentrations and cultured for 4 weeks. Controls with non-transfected MSCs, but exposed to exogenous BMP-2 concentrations on an analogous time profile as that secreted by the Ad-BMP-2 group, were compared. Both the Ad-BMP-2 MSC group and the exogenous protein BMP-2 group strongly expressed osteopontin and bone sialoprotein. Cells secreted a matrix that underwent mineralization on the silk fibroin scaffolds, forming clusters of osseous material, as determined by micro-computed tomography. The expression of osteogenic marker proteins and alkaline phosphatase was significantly higher in the Ad-BMP-2 MSC group than in the exogenous protein BMP-2 group, and no significant differences in mineralization were observed in two of the three MSC sources tested.The results demonstrate that transfection resulted in higher levels of expression of osteogenic marker genes, no change in proliferation rate and did not impact the capacity of the cells to calcify tissues on these protein scaffolds.These findings suggest additional options to control differentiation where exogenous additions of growth factors or morphogens can be replaced with transfected MSCs. Light microscopy of construct cross sections after 2 weeks (A–F) or 4 weeks (G–L) of cultivation in osteogenic medium (B, C, E, F, H, I, K, L) or control medium (A, D, G, J). MSC were either transduced with Ad-BMP-2 (center column) or exposed to BMP-2 concentrations as secreted and measured for the Ad-BMP-2 transduced cells (right column) or cultivated in control medium (left column). Sections were stained with H&E (A–C; G–I) or with von Kossa (D–F; J–L). Bar length is 100 μm. Reprinted from [63], with permission from Elsevier.
© Copyright Policy
Related In: Results  -  Collection

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fig02: Combination of bone tissue engineering, gene therapy based on human mesenchymal stem cells (MSCs) and silk fibroin biomaterials to study the impact of viral transfection on MSC osteogenic performance. MSCs were transduced with adenovirus containing a human BMP-2 (Ad-BMP-2) gene at clinically reasonable viral concentrations and cultured for 4 weeks. Controls with non-transfected MSCs, but exposed to exogenous BMP-2 concentrations on an analogous time profile as that secreted by the Ad-BMP-2 group, were compared. Both the Ad-BMP-2 MSC group and the exogenous protein BMP-2 group strongly expressed osteopontin and bone sialoprotein. Cells secreted a matrix that underwent mineralization on the silk fibroin scaffolds, forming clusters of osseous material, as determined by micro-computed tomography. The expression of osteogenic marker proteins and alkaline phosphatase was significantly higher in the Ad-BMP-2 MSC group than in the exogenous protein BMP-2 group, and no significant differences in mineralization were observed in two of the three MSC sources tested.The results demonstrate that transfection resulted in higher levels of expression of osteogenic marker genes, no change in proliferation rate and did not impact the capacity of the cells to calcify tissues on these protein scaffolds.These findings suggest additional options to control differentiation where exogenous additions of growth factors or morphogens can be replaced with transfected MSCs. Light microscopy of construct cross sections after 2 weeks (A–F) or 4 weeks (G–L) of cultivation in osteogenic medium (B, C, E, F, H, I, K, L) or control medium (A, D, G, J). MSC were either transduced with Ad-BMP-2 (center column) or exposed to BMP-2 concentrations as secreted and measured for the Ad-BMP-2 transduced cells (right column) or cultivated in control medium (left column). Sections were stained with H&E (A–C; G–I) or with von Kossa (D–F; J–L). Bar length is 100 μm. Reprinted from [63], with permission from Elsevier.
Mentions: Meinel et al. transduced MSCs with adenovirus containing a human BMP-2 gene at clinically reasonable viral concentrations and cultured for 4 weeks. Cells secreted a matrix that underwent mineralization on the silk fibroin scaffolds, forming clusters of osseous material and the expression of osteogenic marker proteins, and alkaline phosphates was significantly higher in the Ad-BMP-2 MSC group than in the control group that had received exogenous protein BMP-2. The results demonstrate that transfection resulted in higher levels of expression of osteogenic marker genes, no change in proliferation rate and did not impact the capacity of the cells to calcify tissues on these protein scaffolds, suggesting that exogenous addition of growth factors or morphogens can be replaced with transfected MSCs [63, Fig. 2, printed with permission from Elsevier].

Bottom Line: Techniques of molecular biology can enhance the regenerative potential of a biomaterial by co-delivery of therapeutic genes, and several different strategies have been used to achieve that goal.Possibilities for application are many-fold and have been investigated to regenerate tissues such as skin, cartilage, bone, nerve, liver, pancreas and blood vessels.This review discusses advantages and problems encountered with the different gene delivery strategies as far as they relate to tissue engineering, analyses the positive aspects of polymeric gene delivery from matrices and discusses advances and future challenges of gene transfer strategies in selected tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Plastic and Hand Surgery, University of Erlangen Medical Center, Krankenhausstrasse 12, 91054 Erlangen, Germany.

ABSTRACT
Aiming for regeneration of severed or lost parts of the body, the combined application of gene therapy and tissue engineering has received much attention by regenerative medicine. Techniques of molecular biology can enhance the regenerative potential of a biomaterial by co-delivery of therapeutic genes, and several different strategies have been used to achieve that goal. Possibilities for application are many-fold and have been investigated to regenerate tissues such as skin, cartilage, bone, nerve, liver, pancreas and blood vessels. This review discusses advantages and problems encountered with the different gene delivery strategies as far as they relate to tissue engineering, analyses the positive aspects of polymeric gene delivery from matrices and discusses advances and future challenges of gene transfer strategies in selected tissues.

Show MeSH
Related in: MedlinePlus