Publications (120) View all
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Article: Mesenchymal stem cell chondrogenesis: composite growth factor-bioreactor synergism for human stem cell chondrogenesis.
Marios Petrou, Philipp Niemeyer, Martin J Stoddart, Sibylle Grad, Anke Bernstein, Hermann O Mayr, Gerrit Bode, Norbert Sudkamp, Mauro Alini, Gian M Salzmann[show abstract] [hide abstract]
ABSTRACT: Background: Effective mesenchymal stem cell chondrogenesis can be accomplished by using a tailored mechanical-biochemical stimulus. To achieve this requires parallel suppression of hypertrophy and osteogenesis. Materials & methods: We compared the effects of isolated bioreactor stimulation, isolated growth factor (TGF-β1 or IGF-1) application and their combined stimulation on human bone marrow-derived mesenchymal stem cells cultured within 3D scaffolds. Free-swelling cell-matrix constructs underwent identical growth factor stimulation for control. Results: Mechanical stimulation provoked stronger chondrogenic differentiation than free-swelling culture. Chondrogenesis by the addition of TGF-β1 was enhanced compared with single physical stimulation. There were no such effects under the influence of IGF-1 alone. Composite application of multiaxial mechanical stimulation plus TGF-β1 and IGF-1 not only triggered the strongest chondrogenesis overall, but also the strongest hypertrophy and osteogenesis. Conclusion: Bioreactor-induced chondrogenic differentiation of human mesenchymal stem cells can be effectively enhanced by growth factor addition, while the partially effective suppression of unwanted signs of endochondral ossification requires further scientific input.Regenerative Medicine 03/2013; 8(2):157-70. · 3.72 Impact Factor -
SourceAvailable from: Gianluca Vadalá
Article: The transpedicular approach as an alternative route for intervertebral disc regeneration.
Gianluca Vadalà, Fabrizio Russo, Girish Patappa, Damiano Schiuma, Marianna Peroglio, Lorin Benneker, Sybille Grad, Mauro Alini, Vincenzo Denaro[show abstract] [hide abstract]
ABSTRACT: [ABSTRACT] 300 WORDS: Study Design. Descriptive anatomical study on ovine and human cadaveric lumbar spinal segments.Objective. to describe the alternative transpedicular approach to deliver therapeutic agents into intervertebral disc (IVD).Summary of Background Data. The present delivery approach of therapeutic agents (growth factors/cells/hydrogels) within the IVD is through injection, via the annulus fibrosus (AF). However, it has recently been demonstrated that small needle puncture of the AF leads to further degeneration and disc herniation. In addition, the injected material has a high chance to be extruded through the AF injury.Methods. Lumbar ovine and human spinal segments were used. Under fluoroscopy, a 2mm Kirschner wire was introduced in the caudal vertebra through the pedicle and the inferior endplate to the nucleus pulposus (NP). Gross anatomy analysis and high resolution computed tomography (HR-pQCT) were performed to assess the right position of the wire in pedicles. Discography and nucleotomy were performed using a 14G cannula insertion or a 2 mm arthroscopic shaver blade, respectively. Nucleoplasty was also performed with agarose gel/contrast agent and imaged with HR-pQCT.Results. Gross anatomy, fluoroscopy and HR-pQCT images showed that the NP could be approached through the endplate via the pedicle without affecting the spinal canal and the neural foramina. The contrast agent was delivered into the IVD and NP was removed from the disc and filled with agarose gel.Conclusion. This study describes how a transpedicular approach can be used as an alternative route to deliver therapeutic agents to the disc without disruption of the AF showing the potential use of this technique in preclinical research and highlighting its clinical relevance for IVD regeneration.Spine 01/2013; · 2.08 Impact Factor -
Article: Bioreactor-Induced Chondrocyte Maturation Is Dependent on Cell Passage and Onset of Loading
Ning Wang, Sibylle Grad, Martin J. Stoddart, Philipp Niemeyer, Norbert P. S++dkamp, Jan Pestka, Mauro Alini, Jiying Chen, Gian M. Salzmann[show abstract] [hide abstract]
ABSTRACT: Objective: To explore the effect of shifting in vitro culture conditions regarding cellular passage and onset of loading within matrix-associated bovine articular chondrocytes cultured under free-swelling and/or dynamical loading conditions on general chondrocyte maturation. Methods: Primary or passage 3 bovine chondrocytes were seeded in fibrin-polyurethane scaffolds. Constructs were cultured either free-swelling for 2 or 4 weeks, under direct mechanical loading for 2 or 4 weeks, or free swelling for 2 weeks followed by 2 weeks of loading. Samples were collected for glycosaminoglycan (GAG) quantification, mRNA expression of chondrogenic genes, immunohistochemistry, and histology. Results: Mechanical loading generally stimulated GAG synthesis, up-regulated chondrogenic genes, and improved the accumulation of matrix in cell-laden constructs when compared with free-swelling controls. Primary chondrocytes underwent more effective cartilage maturation when compared with passaged chondrocytes. Constructs ofCartilage 01/2013; -
SourceAvailable from: Daisuke Sakai
Dataset: イメージ3ニッチ
Daisuke Sakai, Yoshihiko Nakamura, Tomoko Nakai, Taishi Mishima, Shunichi Kato, Sibylle Grad, Mauro Alini, Makarand V Risbud, Danny Chan, Kathryn S E Cheah, Ken-Ichi Yamamura, Koichi Masuda, Hideyuki Okano, Kiyoshi Ando, Joji Mochida -
SourceAvailable from: Daisuke Sakai
Dataset: イメージ2 髄核前駆細胞由来コロニー3D
Daisuke Sakai, Yoshihiko Nakamura, Tomoko Nakai, Taishi Mishima, Shunichi Kato, Sibylle Grad, Mauro Alini, Makarand V Risbud, Danny Chan, Kathryn S E Cheah, Ken-Ichi Yamamura, Koichi Masuda, Hideyuki Okano, Kiyoshi Ando, Joji Mochida