Online citations, reference lists, and bibliographies.

Repair Of Chronic Osteochondral Defects Using Predifferentiated Mesenchymal Stem Cells In An Ovine Model

Matthias Zscharnack, Pierre Hepp, Robert Richter, Thomas Aigner, Ronny M. Schulz, Jeremy S Somerson, Christoph Josten, Augustinus Bader, Bastian Marquaß
Published 2010 · Medicine
Cite This
Download PDF
Analyze on Scholarcy
Background: The use of mesenchymal stem cells (MSCs) to treat osteochondral defects caused by sports injuries or disease is of particular interest. However, there is a lack of studies in large-animal models examining the benefits of chondrogenic predifferentiation in vitro for repair of chronic osteochondral defects. Hypothesis: Chondrogenic in vitro predifferentiation of autologous MSCs embedded in a collagen I hydrogel currently in clinical trial use for matrix-associated autologous chondrocyte transplantation facilitates the regeneration of a chronic osteochondral defect in an ovine stifle joint. Study Design: Controlled laboratory study. Methods: The optimal predifferentiation period of ovine MSCs within the type I collagen hydrogel in vitro was defined by assessment of several cellular and molecular biological parameters. For the animal study, osteochondral lesions (diameter 7 mm) were created at the medial femoral condyles of the hind legs in 10 merino sheep. To achieve a chronic defect model, implantation of the ovine MSCs/hydrogel constructs was not performed until 6 weeks after defect creation. The 40 defects were divided into 4 treatment groups: (1) chondrogenically predifferentiated ovine MSC/hydrogel constructs (preMSC-gels), (2) undifferentiated ovine MSC/hydrogel constructs (unMSC-gels), (3) cell-free collagen hydrogels (CF-gels), and (4) untreated controls (UCs). Evaluation followed after 6 months. Results: With regard to proteoglycan content, cell count, gel contraction, apoptosis, compressive properties, and progress of chondrogenic differentiation, a differentiation period of 14 days in vitro was considered optimal. After 6 months in vivo, the defects treated with preMSC-gels showed significantly better histologic scores with morphologic characteristics of hyaline cartilage such as columnarization and presence of collagen type II. Conclusion: Matrix-associated autologous chondrocyte transplantation with predifferentiated MSCs may be a promising approach for repair of focal, chronic osteochondral defects. Clinical Relevance: The results suggest an encouraging method for future treatment of focal osteochondral defects to prevent progression to osteoarthritis.
This paper references
Directing stem cell differentiation into the chondrogenic lineage in vitro.
Boon Chin Heng (2004)
Cartilage tissue engineering by collagen matrix associated bone marrow derived mesenchymal stem cells.
Ronny M. Schulz (2008)
Cartilage regeneration using mesenchymal stem cells and a three-dimensional poly-lactic-glycolic acid (PLGA) scaffold.
Kota Uematsu (2005)
Cartilage repair: generations of autologous chondrocyte transplantation.
Stefan Marlovits (2006)
Enhanced tissue integration during cartilage repair in vitro can be achieved by inhibiting chondrocyte death at the wound edge.
Sophie J. Gilbert (2009)
Microfracture: surgical technique and rehabilitation to treat chondral defects.
J. Richard Steadman (2001)
Joint homeostasis. The discrepancy between old and fresh defects in cartilage repair.
D B F Saris (2003)
Role of mesenchymal stem cells in regenerative medicine: application to bone and cartilage repair.
Froilán Granero-Moltó (2008)
The use of mesenchymal stem cells for chondrogenesis.
Karoliina Pelttari (2008)
The effect of cartilage and bone density of mushroom-shaped, photooxidized, osteochondral transplants: an experimental study on graft performance in sheep using transplants originating from different species
Anja C Waselau (2005)
Perilesional changes of focal osteochondral defects in an ovine model and their relevance to human osteochondral injuries.
Pierre Hepp (2009)
Repair of full-thickness femoral condyle cartilage defects using allogeneic synovial cell-engineered tissue constructs.
Ming Pei (2009)
Repair of osteochondral defects with biphasic cartilage-calcium polyphosphate constructs in a sheep model.
Rita A Kandel (2006)
Stem cell-coated titanium implants for the partial joint resurfacing of the knee.
Karl-Heinz Frosch (2006)
Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)--5-year follow-up.
Peter J. Behrens (2006)
Quantum dots for human mesenchymal stem cells labeling. A size-dependent autophagy activation.
Oleksandr Seleverstov (2006)
Repair of osteochondral defects with hyaluronan- and polyester-based scaffolds.
Luis A. Solchaga (2005)
Repair of superficial osteo - chondral defects with an autologous scaffold - free cartilage construct in a caprine model : implantation method and short - term results
W Brehm (2006)
Histological Assessment of Cartilage Repair: A Report by the Histology Endpoint Committee of the International Cartilage Repair Society (ICRS)
Pierre Mainil-Varlet (2003)
Mechano-regulation of stem cell differentiation and tissue regeneration in osteochondral defects.
Daniel J Kelly (2005)
Autologous Chondrocyte Transplantation
Lars Peterson (2002)
Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects.
Ernst Bruno Hunziker (2002)
Long term in-vivo studies of a photo-oxidized bovine osteochondral transplant in sheep
Margarete K Akens (2001)
Animal models for cartilage reconstruction. Biomaterials
GG Reinholz (2004)
Influence of Scaffold Stiffness on Subchondral Bone and Subsequent Cartilage Regeneration in an Ovine Model of Osteochondral Defect Healing
Karin Schlichting (2008)
Validation of a simple histological-histochemical cartilage scoring system.
Shawn W. O'driscoll (2001)
Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells from bone marrow.
G I Im (2001)
Mesenchymal stem cells: clinical applications and biological characterization.
Frank Barry (2004)
Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage.
Shigeyuki Wakitani (1994)
TGF-beta3: A promising growth factor in engineered organogenesis.
Jinghua Hao (2008)
TGF-β3: A promising growth factor in engineered organogenesis
Jinghua Hao (2008)
Multilineage potential of adult human mesenchymal stem cells.
Mark F. Pittenger (1999)
Osteochondral defect repair using a novel tissue engineering approach: sheep model study.
Robert M. Pilliar (2007)
Animal models for cartilage reconstruction.
Gregory G. Reinholz (2004)
Transplantation of De Novo Scaffold-Free Cartilage Implants into Sheep Knee Chondral Defects
Axel Jubel (2008)
Repair of articular cartilage defects treated by microfracture and a three-dimensional collagen matrix.
Ronald Dorotka (2005)
A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee.
George Bentley (2003)
Repair of superficial osteochondral defects with an autologous scaffold-free cartilage construct in a caprine model: implantation method and short-term results.
Walter Brehm (2006)
Cartilage integration: evaluation of the reasons for failure of integration during cartilage repair. A review.
I M Khan (2008)

This paper is referenced by
Stem Cell Therapies for Knee Cartilage Repair
John A. Anderson (2014)
Prospects and Retrospect of Clinical Applications of Stem Cells in Veterinary Animals
Guttula Taru Sharma (2017)
Cells for Cartilage Regeneration
Gerjo J.V.M. van Osch (2018)
Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics
Giuseppe Filardo (2012)
Preservation of Independent Ambulation 14 Years after Biological Knee Reconstruction: A Case Report
Hisashi Mera (2016)
Biomimetic Approaches for the Engineering of Osteochondral Tissues
Le-Ping Yan (2017)
Age-related morphometric changes of the tidemark in the ovine stifle.
Fanny Hontoir (2019)
Modular assembly for in vitro investigation and engineering of articular cartilage
Benjamin S. Schon (2014)
Mesenchymal stromal cells from unconventional model organisms.
Raquel Calloni (2014)
Engineering articular cartilage from human infrapatellar fat pad stem cells for transplantation therapy
Raed Felimban (2015)
Mesenchymal stem cell-collagen microspheres for articular cartilage repair: cell density and differentiation status.
Y Y Li (2014)
Isolation and morphological characterization of ovine amniotic fluid mesenchymal stem cells
Yunyun Tian (2016)
The Current Status of Preclinical and Clinical Studies
Farshid Guilak (2014)
Engineering of hyaline cartilage with a calcified zone using bone marrow stromal cells.
Whitaik David Lee (2015)
Stem cells and their clinical/therapeutic applications in biomedical and veterinary science - the perspectives.
Amarpal (2013)
Tissue-Engineering Strategies to Repair Chondral and Osteochondral Tissue in Osteoarthritis: Use of Mesenchymal Stem Cells
Susanne Grässel (2014)
Repair of Osteochondral Defects With Predifferentiated Mesenchymal Stem Cells of Distinct Phenotypic Character Derived From a Nanotopographic Platform
Yingnan Wu (2020)
Stem cell-based tissue engineering in veterinary orthopaedics
Walter Brehm (2011)
Temporal activation of β-catenin signaling in the chondrogenic process of mesenchymal stem cells affects the phenotype of the cartilage generated.
Zheng Yang (2012)
Hypoxic culture of bone marrow-derived mesenchymal stromal stem cells differentially enhances in vitro chondrogenesis within cell-seeded collagen and hyaluronic acid porous scaffolds
Troy D. Bornes (2015)
L'Ingénierie tissulaire du cartilage : effet de l'âge du donneur et des contraintes mécanique et chimique du microenvironnement
Ophélie Pollet (2018)
Predifferentiated Mesenchymal Stem Cells for Osteochondral Defects: Letter
Andreas Schmitt (2011)
Repair of articular cartilage defects with intra-articular injection of autologous rabbit synovial fluid-derived mesenchymal stem cells
Zhaofeng Jia (2018)
Isolation and Characterization of CD271+ Stem Cells Derived from Sheep Dermal Skin
Roomina Jahroomishirazi (2014)
Somatic Stem Cells
Shree Ram Singh (2012)
Characterisation and evaluation of the regenerative capacity of Stro-4+ enriched bone marrow mesenchymal stromal cells using bovine extracellular matrix hydrogel and a novel biocompatible melt electro-written medical-grade polycaprolactone scaffold
Cameron R M Black (2020)
Characterization of the cell secretomes from undifferentiated and chondro-induced stem cells —
Inigo Zubiavrre Martinez (2015)
Análisis de un implante para cartílago de células madre mesenquimales modificadas genéticamente con factores condrogénicos en ovis aries
Espinoza Juárez (2012)
Comparison of Undifferentiated Versus Chondrogenic Predifferentiated Mesenchymal Stem Cells Derived From Human Umbilical Cord Blood for Cartilage Repair in a Rat Model
Yong-Beom Park (2019)
Nucleated cells circulating in the peripheral blood contribute to the repair of osteochondral defects only in the early phase of healing.
Tadashi Okano (2014)
Potential for Tumorigenesis and Repair of Osteochondral Defects by iPS Cell Transplantation in Rat
Hisashi Mera (2014)
Use of mesenchymal stem cells seeded on the scaffold in articular cartilage repair
Kaoru Yamagata (2018)
See more
Semantic Scholar Logo Some data provided by SemanticScholar