Chondrogenic commitment of human umbilical cord blood-derived mesenchymal stem cells in collagen matrices for cartilage engineering.
Umbilical cord blood (UCB) is a promising alternative source of mesenchymal stem cells (MSCs), because UCB-MSCs are abundant and harvesting them is a painless non-invasive procedure. Potential clinical applications of UCB-MSCs have been identified, but their ability for chondrogenic differentiation has not yet been fully evaluated. The aim of our work was to characterize and determine the chondrogenic differentiation potential of human UCB-MSCs (hUCB-MSCs) for cartilage tissue engineering using an approach combining 3D culture in type I/III collagen sponges and chondrogenic factors. Our results showed that UCB-MSCs have a high proliferative capacity. These cells differentiated easily into an osteoblast lineage but not into an adipocyte lineage. Furthermore, BMP-2 and TGF-β1 potentiated chondrogenic differentiation, as revealed by a strong increase in mature chondrocyte-specific mRNA (COL2A1, COL2B, ACAN) and protein (type II collagen) markers. Although growth factors increased the transcription of hypertrophic chondrocyte markers such as COL10A1 and MMP13, the cells present in the neo-tissue maintained their phenotype and did not progress to terminal differentiation and mineralization of the extracellular matrix after subcutaneous implantation in nude mice. Our study demonstrates that our culture model has efficient chondrogenic differentiation, and that hUCB-MSCs can be a reliable source for cartilage tissue engineering.
Normandy University, Caen, France; UNICAEN EA4652 MILPAT (Laboratoire Microenvironnement Cellulaire et Pathologies); UFR de Médecine, Université de Caen, Caen Cedex 5, CS14032 Caen, France.
Tangni
T
Gómez-Leduc
Normandy University, Caen, France; UNICAEN EA4652 MILPAT (Laboratoire Microenvironnement Cellulaire et Pathologies); UFR de Médecine, Université de Caen, Caen Cedex 5, CS14032 Caen, France.
Magalie
M
Hervieu
Normandy University, Caen, France; UNICAEN EA4652 MILPAT (Laboratoire Microenvironnement Cellulaire et Pathologies); UFR de Médecine, Université de Caen, Caen Cedex 5, CS14032 Caen, France.
Florence
F
Legendre
Normandy University, Caen, France; UNICAEN EA4652 MILPAT (Laboratoire Microenvironnement Cellulaire et Pathologies); UFR de Médecine, Université de Caen, Caen Cedex 5, CS14032 Caen, France.
Mouloud
M
Bouyoucef
Normandy University, Caen, France; UNICAEN EA4652 MILPAT (Laboratoire Microenvironnement Cellulaire et Pathologies); UFR de Médecine, Université de Caen, Caen Cedex 5, CS14032 Caen, France.|Laboratoire de Cytogénétique Prénatale, Service de Génétique, CHU Caen, France.
Nicolas
N
Gruchy
Normandy University, Caen, France; UNICAEN, INSERM U1199 "Biology and Innovative Therapeutics of Locally Aggressive Cancers" Unit, Caen, France.
Laurent
L
Poulain
Service de Gynécologie-Obstétrique et Médecine de la Reproduction, CHU Caen, France.
Claire
C
de Vienne
Service de Gynécologie-Obstétrique et Médecine de la Reproduction, CHU Caen, France.
Michel
M
Herlicoviez
Normandy University, Caen, France; UNICAEN EA4652 MILPAT (Laboratoire Microenvironnement Cellulaire et Pathologies); UFR de Médecine, Université de Caen, Caen Cedex 5, CS14032 Caen, France.
Magali
M
Demoor
Normandy University, Caen, France; UNICAEN EA4652 MILPAT (Laboratoire Microenvironnement Cellulaire et Pathologies); UFR de Médecine, Université de Caen, Caen Cedex 5, CS14032 Caen, France.
Philippe
P
Galéra
D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002356:Cartilage / Q000166:cytology* / Q000502:physiology; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology; D020219:Chondrogenesis / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D059785:Karyotype; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D008855:Microscopy, Electron, Scanning; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D046509:Tissue Culture Techniques / Q000379:methods; D023822:Tissue Engineering / Q000379:methods*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D055396:Bone Morphogenetic Protein 2; D053773:Transforming Growth Factor beta1; D003094:Collagen