Characterization and use of Equine Bone Marrow Mesenchymal Stem Cells in Equine Cartilage Engineering. Study of their Hyaline Cartilage Forming Potential when Cultured under Hypoxia within a Biomaterial in the Presence of BMP-2 and TGF-ß1.
- Journal Article
Summary
This research article explores how equine bone marrow mesenchymal stem cells (BM-MSCs) can be used and developed into hyaline cartilage through a specific technique, potentially providing a solution for treating musculoskeletal disorders in horses.
Understanding the Study
The researchers have been looking at ways to repair articular cartilage, which does not naturally repair itself well. Damage to this type of cartilage can dramatically impact the performance of sport and racehorses, often leading to early retirement.
- The autologous chondrocyte implantation technique, which has previously been successful with human bone marrow stem cells, was used on horse BM-MSCs in this study.
- This technique required growing the stem cells in 3D collagen sponges, under low-oxygen conditions. Growth factors known to promote the formation of chondrocytes, BMP-2 and TGF-β, were applied to the cells. Additionally, the researchers used siRNA to silence the genes that produce collagen I and HtrA1, trying to stabilize the chondrocyte phenotype.
Key Findings
The BM-MSCs from horse marrow met the criteria for being stem cells, including the ability to proliferate extensively. Researchers found the cells to be very adaptable, showing different characteristics based on the conditions in which they were grown.
- The combination of BMP-2 and TGF-β significantly induced chondrogenic differentiation i.e., they helped stem cells become more similar to chondrocyte (cartilage cells) and prevented the expression of HtrA1, a gene involved in the degradation of extracellular matrix.
- The use of siRNA was successfully able to target and inhibit the collagen I (Col1a1) and HtrA1 gene expression.
- The in vitro (lab) conditions led to the creation of hyaline-type neocartilage. The derived chondrocytes displayed a phenotype similar to healthy, differentiated chondrocytes. This new cartilage potentially holds the key to repairing cartilage damage in horses.
Implications and Future Research
These positive results suggest that pre-clinical trials on horses could be a feasible next step. This future research would help to better understand how the newly-created cartilage integrates into existing tissue, and validate the therapeutic strategy in a large, living model.
Cite This Article
Publication
Researcher Affiliations
- Normandy University, Caen, France.
- UNICAEN BIOTARGEN (Biologie, génétique et thérapies ostéoarticulaires et respiratoires), EA7450; UFR Santé, Université de Caen Normandie, 14000, Caen, France.
- Center of Imaging and Research on Locomotor Affections in Equines, Ecole Vétérinaire d'Alfort, Université Paris-Est, 14430, Goustranville, France.
- Normandy University, Caen, France.
- UNICAEN BIOTARGEN (Biologie, génétique et thérapies ostéoarticulaires et respiratoires), EA7450; UFR Santé, Université de Caen Normandie, 14000, Caen, France.
- Normandy University, Caen, France.
- UNICAEN BIOTARGEN (Biologie, génétique et thérapies ostéoarticulaires et respiratoires), EA7450; UFR Santé, Université de Caen Normandie, 14000, Caen, France.
- Normandy University, Caen, France.
- UNICAEN BIOTARGEN (Biologie, génétique et thérapies ostéoarticulaires et respiratoires), EA7450; UFR Santé, Université de Caen Normandie, 14000, Caen, France.
- Normandy University, Caen, France.
- UNICAEN BIOTARGEN (Biologie, génétique et thérapies ostéoarticulaires et respiratoires), EA7450; UFR Santé, Université de Caen Normandie, 14000, Caen, France.
- Normandy University, Caen, France.
- UNICAEN BIOTARGEN (Biologie, génétique et thérapies ostéoarticulaires et respiratoires), EA7450; UFR Santé, Université de Caen Normandie, 14000, Caen, France.
- Normandy University, Caen, France.
- UNICAEN BIOTARGEN (Biologie, génétique et thérapies ostéoarticulaires et respiratoires), EA7450; UFR Santé, Université de Caen Normandie, 14000, Caen, France.
- Center of Imaging and Research on Locomotor Affections in Equines, Ecole Vétérinaire d'Alfort, Université Paris-Est, 14430, Goustranville, France.
- Center of Imaging and Research on Locomotor Affections in Equines, Ecole Vétérinaire d'Alfort, Université Paris-Est, 14430, Goustranville, France.
- Center of Imaging and Research on Locomotor Affections in Equines, Ecole Vétérinaire d'Alfort, Université Paris-Est, 14430, Goustranville, France.
- Normandy University, Caen, France.
- UNICAEN BIOTARGEN (Biologie, génétique et thérapies ostéoarticulaires et respiratoires), EA7450; UFR Santé, Université de Caen Normandie, 14000, Caen, France.
- Normandy University, Caen, France. philippe.galera@unicaen.fr.
- UNICAEN BIOTARGEN (Biologie, génétique et thérapies ostéoarticulaires et respiratoires), EA7450; UFR Santé, Université de Caen Normandie, 14000, Caen, France. philippe.galera@unicaen.fr.
MeSH Terms
- Animals
- Bone Marrow Cells / cytology
- Bone Marrow Cells / drug effects
- Bone Marrow Cells / metabolism
- Bone Morphogenetic Protein 2 / pharmacology
- Cell Differentiation / drug effects
- Cell Hypoxia
- Cell Proliferation / drug effects
- Chondrocytes / cytology
- Chondrocytes / drug effects
- Chondrocytes / metabolism
- Chondrogenesis / drug effects
- Chondrogenesis / genetics
- Collagen Type I / antagonists & inhibitors
- Collagen Type I / genetics
- Collagen Type I / metabolism
- Collagen Type I, alpha 1 Chain
- Gene Expression Regulation
- High-Temperature Requirement A Serine Peptidase 1 / antagonists & inhibitors
- High-Temperature Requirement A Serine Peptidase 1 / genetics
- High-Temperature Requirement A Serine Peptidase 1 / metabolism
- Horses
- Hyaline Cartilage / cytology
- Hyaline Cartilage / metabolism
- Mesenchymal Stem Cells / cytology
- Mesenchymal Stem Cells / drug effects
- Mesenchymal Stem Cells / metabolism
- Primary Cell Culture
- RNA, Small Interfering / genetics
- RNA, Small Interfering / metabolism
- Signal Transduction
- Tissue Engineering / methods
- Transforming Growth Factor beta1 / pharmacology
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