Tenogenic differentiation of equine adipose-tissue-derived stem cells under the influence of tensile strain, growth differentiation factors and various oxygen tensions.
Abstract: Mesenchymal stem cells have become extremely interesting for regenerative medicine and tissue engineering in the horse. Stem cell therapy has been proven to be a powerful and successful instrument, in particular for the healing of tendon lesions. We pre-differentiated equine adipose-tissue-derived stem cells (ASCs) in a collagen I gel scaffold by applying tensile strain, growth differentiation factors (GDFs) and various oxygen tensions in order to determine the optimal conditions for in vitro differentiation toward the tenogenic lineage. We compared the influence of 3% versus 21% oxygen tension, the use of GDF 5, GDF 6 and GDF 7 and the application of uniaxial tensile strain versus no mechanical stimulation on differentiation results as evaluated by cell morphology and by the expression of the tendon-relevant genes collagen I, collagen III, cartilage oligomeric matrix protein and scleraxis. The best results were obtained with an oxygen tension of 21%, tensile stimulation and supplementation with GDF 5 or GDF 7. This approach raises the hope that the in vivo application of pre-differentiated stem cells will improve healing and recovery time in comparison with treatment involving undifferentiated stem cells.
Publication Date: 2013-02-22 PubMed ID: 23430474DOI: 10.1007/s00441-013-1574-1Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This study explores optimal conditions for differentiating stem cells extracted from horse fat tissue suited for treating tendon injuries. It found that best results were achieved by subjecting the cells to 21% oxygen tension, physical stretching, and bolstering with certain growth differentiation factors.
Objective and Scope of the Research
The research investigates a more effective stem cell-based therapy for tendon injuries in horses. Specifically, the researchers attempted to determine the best conditions for differentiating equine adipose-tissue-derived stem cells (ASCs), aiming to develop a tailored treatment protocol for repairing tendon lesions.
Methodology
- The team extracted mesenchymal stem cells (a type of stem cell that can differentiate into multiple cell types) from horse adipose tissue (fat).
- These adipose-tissue-derived stem cells (ASCs) were pre-differentiated in a collagen I gel scaffold, a substance that provides support for cell growth and differentiation.
- Differentiation conditions were altered using varying levels of oxygen tension, specific Growth Differentiation Factors (GDFs), and the application of uniaxial tensile strain (physical stretching).
Variable Testing
- The effect of oxygen tension was tested with concentrations of 3% and 21%.
- Growth Differentiation Factors used were GDF 5, 6, and 7, biological substances that regulate cellular activities, including differentiation.
- Half the stem cells were subjected to uniaxial tensile strain while the other half did not receive any mechanical stimulation.
Evaluating Results
- The ability of ASCs to differentiate into tenocytes (tendon cells) under different conditions was assessed by evaluating cellular morphology and examining the expression of tendon-relevant genes such as collagen I, collagen III, cartilage oligomeric matrix protein, and scleraxis.
- The experiment concluded with optimal differentiation achieved with an oxygen tension of 21%, tensile stimulation, and supplementation with GDF 5 or GDF 7.
Significance and Implications
- This research offers a potentially improved healing method for horses with tendon lesions by utilising pre-differentiated, rather than undifferentiated, stem cells for therapy.
- Understanding the influence of environmental conditions on stem cell differentiation can direct the further development of more efficient, targeted cell-based therapies in veterinary medicine.
Cite This Article
APA
Raabe O, Shell K, Fietz D, Freitag C, Ohrndorf A, Christ HJ, Wenisch S, Arnhold S.
(2013).
Tenogenic differentiation of equine adipose-tissue-derived stem cells under the influence of tensile strain, growth differentiation factors and various oxygen tensions.
Cell Tissue Res, 352(3), 509-521.
https://doi.org/10.1007/s00441-013-1574-1 Publication
Researcher Affiliations
- Institute of Veterinary Anatomy, Histology, and Embryology, Justus-Liebig University of Giessen, Frankfurterstrasse 98, 35392, Giessen, Germany. Oksana.Raabe@vetmed.uni-giessen.de
MeSH Terms
- Adipose Tissue / cytology
- Animals
- Biomarkers / metabolism
- Bioreactors
- Cell Communication / drug effects
- Cell Differentiation / drug effects
- Cell Lineage / drug effects
- Cell Shape / drug effects
- Collagen Type I / pharmacology
- Gels
- Gene Expression Regulation / drug effects
- Growth Differentiation Factors / pharmacology
- Horses
- Immunohistochemistry
- Intercellular Junctions / drug effects
- Intercellular Junctions / metabolism
- Oxygen / pharmacology
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Rats
- Stem Cells / cytology
- Stem Cells / drug effects
- Stem Cells / ultrastructure
- Tendons / cytology
- Tensile Strength / drug effects
- Tissue Scaffolds
Citations
This article has been cited 29 times.- Klymiuk MC, Speer J, Marco I, Elashry MI, Heimann M, Wenisch S, Arnhold S. Determination of the miRNA profile of extracellular vesicles from equine mesenchymal stem cells after different treatments. Stem Cell Res Ther 2025 Apr 5;16(1):162.
- Haidar-Montes AA, Mauro A, El Khatib M, Prencipe G, Pierdomenico L, Tosi U, Wouters G, Cerveró-Varona A, Berardinelli P, Russo V, Barboni B. Mechanobiological Strategies to Enhance Ovine (Ovis aries) Adipose-Derived Stem Cells Tendon Plasticity for Regenerative Medicine and Tissue Engineering Applications. Animals (Basel) 2024 Jul 31;14(15).
- Klymiuk MC, Balz N, Elashry MI, Wenisch S, Arnhold S. Effect of storage conditions on the quality of equine and canine mesenchymal stem cell derived nanoparticles including extracellular vesicles for research and therapy. Discov Nano 2024 May 3;19(1):80.
- Abdalla AA, Pendegrass CJ. Biological approaches to the repair and regeneration of the rotator cuff tendon-bone enthesis: a literature review. Biomater Transl 2023;4(2):85-103.
- Citro V, Clerici M, Boccaccini AR, Della Porta G, Maffulli N, Forsyth NR. Tendon tissue engineering: An overview of biologics to promote tendon healing and repair. J Tissue Eng 2023 Jan-Dec;14:20417314231196275.
- Shojaee A. Equine tendon mechanical behaviour: Prospects for repair and regeneration applications. Vet Med Sci 2023 Sep;9(5):2053-2069.
- Deng R, Kang R, Jin X, Wang Z, Liu X, Wang Q, Xie L. Mechanical stimulation promotes MSCs healing the lesion of intervertebral disc annulus fibrosus. Front Bioeng Biotechnol 2023;11:1137199.
- Shiroud Heidari B, Ruan R, Vahabli E, Chen P, De-Juan-Pardo EM, Zheng M, Doyle B. Natural, synthetic and commercially-available biopolymers used to regenerate tendons and ligaments. Bioact Mater 2023 Jan;19:179-197.
- Wee J, Kim H, Shin SJ, Lee T, Lee SY. Influence of mechanical and TGF-β3 stimulation on the tenogenic differentiation of tonsil-derived mesenchymal stem cells. BMC Mol Cell Biol 2022 Jan 15;23(1):3.
- Fitzgerald MJ, Mustapich T, Liang H, Larsen CG, Nellans KW, Grande DA. Tendon Transection Healing Can Be Improved With Adipose-Derived Stem Cells Cultured With Growth Differentiation Factor 5 and Platelet-Derived Growth Factor. Hand (N Y) 2023 May;18(3):436-445.
- Younesi Soltani F, Javanshir S, Dowlati G, Parham A, Naderi-Meshkin H. Differentiation of human adipose-derived mesenchymal stem cells toward tenocyte by platelet-derived growth factor-BB and growth differentiation factor-6. Cell Tissue Bank 2022 Jun;23(2):237-246.
- Stanco D, Boffito M, Bogni A, Puricelli L, Barrero J, Soldati G, Ciardelli G. 3D Bioprinting of Human Adipose-Derived Stem Cells and Their Tenogenic Differentiation in Clinical-Grade Medium. Int J Mol Sci 2020 Nov 18;21(22).
- Sheng R, Jiang Y, Backman LJ, Zhang W, Chen J. The Application of Mechanical Stimulations in Tendon Tissue Engineering. Stem Cells Int 2020;2020:8824783.
- Javanshir S, Younesi Soltani F, Dowlati G, Parham A, Naderi-Meshkin H. Induction of tenogenic differentiation of equine adipose-derived mesenchymal stem cells by platelet-derived growth factor-BB and growth differentiation factor-6. Mol Biol Rep 2020 Sep;47(9):6855-6862.
- Shojaee A, Parham A. Strategies of tenogenic differentiation of equine stem cells for tendon repair: current status and challenges. Stem Cell Res Ther 2019 Jun 18;10(1):181.
- Klymiuk MC, Balz N, Elashry MI, Heimann M, Wenisch S, Arnhold S. Exosomes isolation and identification from equine mesenchymal stem cells. BMC Vet Res 2019 Jan 28;15(1):42.
- Frauz K, Teodoro LFR, Carneiro GD, Cristina da Veiga F, Lopes Ferrucci D, Luis Bombeiro A, Waleska Simões P, Elvira Álvares L, Leite R de Oliveira A, Pontes Vicente C, Seabra Ferreira R Jr, Barraviera B, do Amaral MEC, Augusto M Esquisatto M, de Campos Vidal B, Rosa Pimentel E, Aparecida de Aro A. Transected Tendon Treated with a New Fibrin Sealant Alone or Associated with Adipose-Derived Stem Cells. Cells 2019 Jan 16;8(1).
- Norelli JB, Plaza DP, Stal DN, Varghese AM, Liang H, Grande DA. Tenogenically differentiated adipose-derived stem cells are effective in Achilles tendon repair in vivo. J Tissue Eng 2018 Jan-Dec;9:2041731418811183.
- Zhou K, Feng B, Wang W, Jiang Y, Zhang W, Zhou G, Jiang T, Cao Y, Liu W. Nanoscaled and microscaled parallel topography promotes tenogenic differentiation of ASC and neotendon formation in vitro. Int J Nanomedicine 2018;13:3867-3881.
- Pöschke A, Krähling B, Failing K, Staszyk C. Molecular Characteristics of the Equine Periodontal Ligament. Front Vet Sci 2017;4:235.
- Geburek F, Roggel F, van Schie HTM, Beineke A, Estrada R, Weber K, Hellige M, Rohn K, Jagodzinski M, Welke B, Hurschler C, Conrad S, Skutella T, van de Lest C, van Weeren R, Stadler PM. Effect of single intralesional treatment of surgically induced equine superficial digital flexor tendon core lesions with adipose-derived mesenchymal stromal cells: a controlled experimental trial. Stem Cell Res Ther 2017 Jun 5;8(1):129.
- Yang G, Rothrauff BB, Lin H, Yu S, Tuan RS. Tendon-Derived Extracellular Matrix Enhances Transforming Growth Factor-β3-Induced Tenogenic Differentiation of Human Adipose-Derived Stem Cells. Tissue Eng Part A 2017 Feb;23(3-4):166-176.
- Burk J, Plenge A, Brehm W, Heller S, Pfeiffer B, Kasper C. Induction of Tenogenic Differentiation Mediated by Extracellular Tendon Matrix and Short-Term Cyclic Stretching. Stem Cells Int 2016;2016:7342379.
- Trumbull A, Subramanian G, Yildirim-Ayan E. Mechanoresponsive musculoskeletal tissue differentiation of adipose-derived stem cells. Biomed Eng Online 2016 Apr 22;15:43.
- Rehmann MS, Luna JI, Maverakis E, Kloxin AM. Tuning microenvironment modulus and biochemical composition promotes human mesenchymal stem cell tenogenic differentiation. J Biomed Mater Res A 2016 May;104(5):1162-74.
- Arnhold S, Wenisch S. Adipose tissue derived mesenchymal stem cells for musculoskeletal repair in veterinary medicine. Am J Stem Cells 2015;4(1):1-12.
- Burk J, Gittel C, Heller S, Pfeiffer B, Paebst F, Ahrberg AB, Brehm W. Gene expression of tendon markers in mesenchymal stromal cells derived from different sources. BMC Res Notes 2014 Nov 20;7:826.
- Mohanty N, Gulati BR, Kumar R, Gera S, Kumar P, Somasundaram RK, Kumar S. Immunophenotypic characterization and tenogenic differentiation of mesenchymal stromal cells isolated from equine umbilical cord blood. In Vitro Cell Dev Biol Anim 2014 Jun;50(6):538-48.
- Yang G, Rothrauff BB, Lin H, Gottardi R, Alexander PG, Tuan RS. Enhancement of tenogenic differentiation of human adipose stem cells by tendon-derived extracellular matrix. Biomaterials 2013 Dec;34(37):9295-306.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists