Myogenic differentiation of mesenchymal stem cells in a newly developed neurotised AV-loop model

TY - JOUR

T1 - Myogenic differentiation of mesenchymal stem cells in a newly developed neurotised AV-loop model

AU - Bitto, Franz F

AU - Klumpp, Dorothee

AU - Lange, Claudia

AU - Boos, Anja M

AU - Arkudas, Andreas

AU - Bleiziffer, Oliver

AU - Horch, Raymund E

AU - Kneser, Ulrich

AU - Beier, Justus P

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Generation of axially vascularized muscle tissue constitutes a promising new approach to restoration of damaged muscle tissue. Mesenchymal stemcells (MSC), with their ability to be expanded to large cell numbers without losing their differentiation capacity into the myogenic lineage, could offer a promising cell source to generate neomuscle tissue. In vitro experiments showed that cocultures of primary myoblasts and MSC undergo myogenic differentiation by stimulation with bFGF and dexamethasone. A newly developed AV-Loop model with neurotization was established in this study. It encompasses axial vascularization and the additional implantation of a motor nerve serving as myogenic stimulator. Myoblasts and MSCs were coimplantated in a prevascularized isolation chamber. Cells were differentiated by addition of bFGF and dexamethasone plus implantation of a motor nerve. After 8 weeks, we could observe areas of myogenic differentiation with α -sarcomeric actin and MHC expression in the constructs. Quantitative PCR analysis showed an expression of myogenic markers in all specimens. Thus, neurotization and addition of bFGF and dexamethasone allow myogenic differentiation of MSC in an axially vascularized in vivo model for the first time. These findings are a new step towards clinical applicability of skeletal muscle tissue engineering and display its potential for regenerative medicine.

AB - Generation of axially vascularized muscle tissue constitutes a promising new approach to restoration of damaged muscle tissue. Mesenchymal stemcells (MSC), with their ability to be expanded to large cell numbers without losing their differentiation capacity into the myogenic lineage, could offer a promising cell source to generate neomuscle tissue. In vitro experiments showed that cocultures of primary myoblasts and MSC undergo myogenic differentiation by stimulation with bFGF and dexamethasone. A newly developed AV-Loop model with neurotization was established in this study. It encompasses axial vascularization and the additional implantation of a motor nerve serving as myogenic stimulator. Myoblasts and MSCs were coimplantated in a prevascularized isolation chamber. Cells were differentiated by addition of bFGF and dexamethasone plus implantation of a motor nerve. After 8 weeks, we could observe areas of myogenic differentiation with α -sarcomeric actin and MHC expression in the constructs. Quantitative PCR analysis showed an expression of myogenic markers in all specimens. Thus, neurotization and addition of bFGF and dexamethasone allow myogenic differentiation of MSC in an axially vascularized in vivo model for the first time. These findings are a new step towards clinical applicability of skeletal muscle tissue engineering and display its potential for regenerative medicine.

KW - Animals

KW - Cell Differentiation

KW - Cell Lineage

KW - Coculture Techniques

KW - Dexamethasone

KW - Fibroblast Growth Factors

KW - Humans

KW - Mesenchymal Stromal Cells

KW - Muscle, Skeletal

KW - Myoblasts

KW - Rats

KW - Regenerative Medicine

KW - Tissue Engineering

U2 - 10.1155/2013/935046

DO - 10.1155/2013/935046

M3 - SCORING: Journal article

C2 - 24106724

VL - 2013

SP - 935046

JO - BIOMED RES INT

JF - BIOMED RES INT

SN - 2314-6133

ER -