siRNA nanoparticle functionalization of nanostructured scaffolds enables controlled multilineage differentiation of stem cells

TY - JOUR

T1 - siRNA nanoparticle functionalization of nanostructured scaffolds enables controlled multilineage differentiation of stem cells

AU - Andersen, Morten Ø

AU - Nygaard, Jens V

AU - Burns, Jorge S

AU - Raarup, Merete K

AU - Nyengaard, Jens R

AU - Bünger, Cody

AU - Besenbacher, Flemming

AU - Howard, Kenneth A

AU - Kassem, Moustapha

AU - Kjems, Jørgen

PY - 2010

Y1 - 2010

N2 - The creation of complex tissues and organs is the ultimate goal in tissue engineering. Engineered morphogenesis necessitates spatially controlled development of multiple cell types within a scaffold implant. We present a novel method to achieve this by adhering nanoparticles containing different small-interfering RNAs (siRNAs) into nanostructured scaffolds. This allows spatial retention of the RNAs within nanopores until their cellular delivery. The released siRNAs were capable of gene silencing BCL2L2 and TRIB2, in mesenchymal stem cells (MSCs), enhancing osteogenic and adipogenic differentiation, respectively. This approach for enhancing a single type of differentiation is immediately applicable to all areas of tissue engineering. Different nanoparticles localized to spatially distinct locations within a single implant allowed two different tissue types to develop in controllable areas of an implant. As a consequence of this, we predict that complex tissues and organs can be engineered by the in situ development of multiple cell types guided by spatially restricted nanoparticles.

AB - The creation of complex tissues and organs is the ultimate goal in tissue engineering. Engineered morphogenesis necessitates spatially controlled development of multiple cell types within a scaffold implant. We present a novel method to achieve this by adhering nanoparticles containing different small-interfering RNAs (siRNAs) into nanostructured scaffolds. This allows spatial retention of the RNAs within nanopores until their cellular delivery. The released siRNAs were capable of gene silencing BCL2L2 and TRIB2, in mesenchymal stem cells (MSCs), enhancing osteogenic and adipogenic differentiation, respectively. This approach for enhancing a single type of differentiation is immediately applicable to all areas of tissue engineering. Different nanoparticles localized to spatially distinct locations within a single implant allowed two different tissue types to develop in controllable areas of an implant. As a consequence of this, we predict that complex tissues and organs can be engineered by the in situ development of multiple cell types guided by spatially restricted nanoparticles.

U2 - 10.1038/mt.2010.166

DO - 10.1038/mt.2010.166

M3 - Journal article

C2 - 20808289

SN - 1525-0016

VL - 18

SP - 2018

EP - 2027

JO - Molecular Therapy

JF - Molecular Therapy

IS - 11

ER -