FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
European cells & materials2018; 36; 156-170; doi: 10.22203/eCM.v036a12

Lentiviral-based reporter constructs for profiling chondrogenic activity in primary equine cell populations.

Abstract: Successful clinical translation of mesenchymal stem cell (MSC)-based therapies for cartilage repair will likely require the implementation of standardised protocols and broadly applicable tools to facilitate the comparisons among cell types and chondroinduction methods. The present study investigated the utility of recombinant lentiviral reporter vectors as reliable tools for comparing chondrogenic potential among primary cell populations and distinguishing cellular-level variations of chondrogenic activity in widely used three-dimensional (3D) culture systems. Primary equine MSCs and chondrocytes were transduced with vectors containing combinations of fluorescent and luciferase reporter genes under constitutive cytomeglavirus (CMV) or chondrocyte-lineage (Col2) promoters. Reporter activity was measured by fluorescence imaging and luciferase assay. In 3D cultures of MSC aggregates and polyethylene glycol-hyaluronic acid (PEG-HA) hydrogels, transforming growth factor beta 3 (TGF-β3)-mediated chondroinduction increased Col2 reporter activity, demonstrating close correlation with histology and mRNA expression levels of COL2A1 and SOX9. Comparison of chondrogenic activities among MSC populations using a secretable luciferase reporter revealed enhanced chondrogenesis in bone-marrow-derived MSCs relative to MSC populations from synovium and adipose tissues. A dual fluorescence reporter - enabling discrimination of highly chondrogenic (Col2-GFP) cells within an MSC population (CMV-tdTomato) - revealed marked heterogeneity in differentiating aggregate cultures and identified chondrogenic cells in chondrocyte-seeded PEG-HA hydrogels after 6 weeks in a subcutaneous implant model - indicating stable, long-term reporter expression in vivo. These results suggested that lentiviral reporter vectors may be used to address fundamental questions regarding chondrogenic activity in chondroprogenitor cell populations and accelerate clinical translation of cell-based cartilage repair strategies.
Get Full Text
Publication Date: 2018-10-12 PubMed ID: 30311630PubMed Central: PMC6788286DOI: 10.22203/eCM.v036a12Google 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.
LinkedInCopy
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • 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.

The research article discusses the utility of lentiviral reporter vectors as tools for comparing the potential to develop into cartilage among different primary cell populations. The study used equine MSCs and chondrocytes and found that these vectors can be used effectively in common three-dimensional cell culture systems. The study also brought light to differences in the chondrogenic activity among different types of MSCs.

Objective of the Research

  • The objective of the research was to test the utility of recombinant lentiviral reporter vectors as tools for comparing the chondrogenic activity among various primary cell populations. The study further aimed to investigate variability in chondrogenic activity in widely used three-dimensional (3D) culture systems.

Methodology and Findings

  • The researchers used primary equine mesenchymal stem cells (MSCs) and chondrocytes, which were transduced with vectors containing a combination of fluorescent and luciferase reporter genes under constitutive cytomegalovirus (CMV) or chondrocyte-lineage (Col2) promoters.
  • They then measured the reporter activity using fluorescence imaging and luciferase assays.
  • Furthermore, they discovered that in 3D cultures of MSC aggregates and polyethylene glycol-hyaluronic acid (PEG-HA) hydrogels, transforming growth factor beta 3 (TGF-β3) increased Col2 reporter activity, showing a close correlation with histology and mRNA expression levels of COL2A1 and SOX9.
  • The research revealed enhanced chondrogenesis in bone-marrow-derived MSCs compared to MSC populations from synovium and adipose tissues when using a secretable luciferase reporter.

Significant Conclusions

  • A crucial finding was that a dual fluorescence reporter could distinguish highly chondrogenic cells (Col2-GFP) within an MSC population. This indicative of marked heterogeneity in differentiating aggregate cultures was identified.
  • Moreover, the study revealed that this system could detect chondrogenic cells in chondrocyte-seeded PEG-HA hydrogels after six weeks in a subcutaneous implant model, indicating stable, long-term reporter expression in vivo.
  • Collectively, the findings suggested that lentiviral reporter vectors might be a helpful tool to explore fundamental questions regarding chondrogenic activity in chondroprogenitor cell populations and could potentially accelerate the clinical translation of cell-based cartilage repair strategies.

Cite This Article

APA
Martin-Pena A, Porter RM, Plumton G, McCarrel TM, Morton AJ, Guijarro MV, Ghivizzani SC, Sharma B, Palmer GD. (2018). Lentiviral-based reporter constructs for profiling chondrogenic activity in primary equine cell populations. Eur Cell Mater, 36, 156-170. https://doi.org/10.22203/eCM.v036a12

Publication

European cells & materials
ISSN: 1473-2262
NlmUniqueID: 100973416
Country: Switzerland
Language: English
Volume: 36
Pages: 156-170

Researcher Affiliations

Martin-Pena, A
    Porter, R M
      Plumton, G
        McCarrel, T M
          Morton, A J
            Guijarro, M V
              Ghivizzani, S C
                Sharma, B
                  Palmer, G D
                  • Department of Orthopaedics and Rehabilitation, University of Florida, 1600 SW Archer Rd, MSB, M2-235, Gainesville, FL, 32610, USA.glynpal@gmail.com.

                  MeSH Terms

                  • Animals
                  • Cell Aggregation
                  • Cell Differentiation
                  • Cells, Cultured
                  • Chondrocytes / cytology
                  • Chondrocytes / metabolism
                  • Chondrogenesis
                  • Collagen Type II / genetics
                  • Collagen Type II / metabolism
                  • Fluorescence
                  • Genes, Reporter
                  • Horses
                  • Hyaluronic Acid / pharmacology
                  • Hydrogen / pharmacology
                  • Implants, Experimental
                  • Lentivirus / genetics
                  • Luciferases / metabolism
                  • Mesenchymal Stem Cells / cytology
                  • Mesenchymal Stem Cells / metabolism
                  • Polyethylene Glycols / pharmacology
                  • Promoter Regions, Genetic / genetics

                  Grant Funding

                  • R21 AR069844 / NIAMS NIH HHS

                  References

                  This article includes 59 references
                  1. Anderson DE, Markway BD, Bond D, McCarthy HE, Johnstone B. Responses to altered oxygen tension are distinct between human stem cells of high and low chondrogenic capacity.. Stem Cell Res Ther 2016 Oct 20;7(1):154.
                    pmc: PMC5073443pubmed: 27765063doi: 10.1186/s13287-016-0419-8google scholar: lookup
                  2. Bornes TD, Adesida AB, Jomha NM. Mesenchymal stem cells in the treatment of traumatic articular cartilage defects: a comprehensive review.. Arthritis Res Ther 2014;16(5):432.
                    pmc: PMC4289291pubmed: 25606595doi: 10.1186/s13075-014-0432-1google scholar: lookup
                  3. Boyette LB, Creasey OA, Guzik L, Lozito T, Tuan RS. Human bone marrow-derived mesenchymal stem cells display enhanced clonogenicity but impaired differentiation with hypoxic preconditioning.. Stem Cells Transl Med 2014 Feb;3(2):241-54.
                    pmc: PMC3925051pubmed: 24436440doi: 10.5966/sctm.2013-0079google scholar: lookup
                  4. Cohen S, Samadikuchaksaraei A, Polak JM, Bishop AE. Antibiotics reduce the growth rate and differentiation of embryonic stem cell cultures.. Tissue Eng 2006 Jul;12(7):2025-30.
                    pubmed: 16889530doi: 10.1089/ten.2006.12.2025google scholar: lookup
                  5. Connell JP, Augustini E, Cheng S, Benavides OM, Ruano R, Jacot JG. Effect of passage, sorting, and media on differentiation capacity and marker expression in amniotic fluid stem cells.. Cel Mol Bioeng 2016;9:139–150.
                  6. Danisovic L, Varga I, Polák S, Ulicná M, Hlavacková L, Böhmer D, Vojtassák J. Comparison of in vitro chondrogenic potential of human mesenchymal stem cells derived from bone marrow and adipose tissue.. Gen Physiol Biophys 2009 Mar;28(1):56-62.
                    pubmed: 19390137
                  7. Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D, Naldini L. A third-generation lentivirus vector with a conditional packaging system.. J Virol 1998 Nov;72(11):8463-71.
                    pmc: PMC110254pubmed: 9765382doi: 10.1128/jvi.72.11.8463-8471.1998google scholar: lookup
                  8. Estes BT, Wu AW, Guilak F. Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6.. Arthritis Rheum 2006 Apr;54(4):1222-32.
                    pubmed: 16572454doi: 10.1002/art.21779google scholar: lookup
                  9. Goldberg A, Mitchell K, Soans J, Kim L, Zaidi R. The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.. J Orthop Surg Res 2017 Mar 9;12(1):39.
                    pmc: PMC5345159pubmed: 28279182doi: 10.1186/s13018-017-0534-ygoogle scholar: lookup
                  10. He F, Chen X, Pei M. Reconstruction of an in vitro tissue-specific microenvironment to rejuvenate synovium-derived stem cells for cartilage tissue engineering.. Tissue Eng Part A 2009 Dec;15(12):3809-21.
                    pubmed: 19545204doi: 10.1089/ten.tea.2009.0188google scholar: lookup
                  11. Hennig T, Lorenz H, Thiel A, Goetzke K, Dickhut A, Geiger F, Richter W. Reduced chondrogenic potential of adipose tissue derived stromal cells correlates with an altered TGFbeta receptor and BMP profile and is overcome by BMP-6.. J Cell Physiol 2007 Jun;211(3):682-91.
                    pubmed: 17238135doi: 10.1002/jcp.20977google scholar: lookup
                  12. Hirschhaeuser F, Menne H, Dittfeld C, West J, Mueller-Klieser W, Kunz-Schughart LA. Multicellular tumor spheroids: an underestimated tool is catching up again.. J Biotechnol 2010 Jul 1;148(1):3-15.
                    pubmed: 20097238doi: 10.1016/j.jbiotec.2010.01.012google scholar: lookup
                  13. Huang YZ, Xie HQ, Silini A, Parolini O, Zhang Y, Deng L, Huang YC. Mesenchymal Stem/Progenitor Cells Derived from Articular Cartilage, Synovial Membrane and Synovial Fluid for Cartilage Regeneration: Current Status and Future Perspectives.. Stem Cell Rev Rep 2017 Oct;13(5):575-586.
                    pubmed: 28721683doi: 10.1007/s12015-017-9753-1google scholar: lookup
                  14. Hung CT, Henshaw DR, Wang CC, Mauck RL, Raia F, Palmer G, Chao PH, Mow VC, Ratcliffe A, Valhmu WB. Mitogen-activated protein kinase signaling in bovine articular chondrocytes in response to fluid flow does not require calcium mobilization.. J Biomech 2000 Jan;33(1):73-80.
                    pubmed: 10609520doi: 10.1016/s0021-9290(99)00176-1google scholar: lookup
                  15. Hurtig MB, Buschmann MD, Fortier LA, Hoemann CD, Hunziker EB, Jurvelin JS, Mainil-Varlet P, McIlwraith CW, Sah RL, Whiteside RA. Preclinical Studies for Cartilage Repair: Recommendations from the International Cartilage Repair Society.. Cartilage 2011 Apr;2(2):137-52.
                    pmc: PMC4300779pubmed: 26069576doi: 10.1177/1947603511401905google scholar: lookup
                  16. Jayasuriya CT, Chen Q. Potential benefits and limitations of utilizing chondroprogenitors in cell-based cartilage therapy.. Connect Tissue Res 2015;56(4):265-71.
                    pmc: PMC4772698pubmed: 26075411doi: 10.3109/03008207.2015.1040547google scholar: lookup
                  17. Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells.. Exp Cell Res 1998 Jan 10;238(1):265-72.
                    pubmed: 9457080doi: 10.1006/excr.1997.3858google scholar: lookup
                  18. Kan A, Ikeda T, Saito T, Yano F, Fukai A, Hojo H, Ogasawara T, Ogata N, Nakamura K, Chung UI, Kawaguchi H. Screening of chondrogenic factors with a real-time fluorescence-monitoring cell line ATDC5-C2ER: identification of sorting nexin 19 as a novel factor.. Arthritis Rheum 2009 Nov;60(11):3314-23.
                    pubmed: 19877062doi: 10.1002/art.24878google scholar: lookup
                  19. Khan WS, Adesida AB, Tew SR, Longo UG, Hardingham TE. Fat pad-derived mesenchymal stem cells as a potential source for cell-based adipose tissue repair strategies.. Cell Prolif 2012 Apr;45(2):111-20.
                    pmc: PMC6496625pubmed: 22260253doi: 10.1111/j.1365-2184.2011.00804.xgoogle scholar: lookup
                  20. Kim JH, Lee SR, Li LH, Park HJ, Park JH, Lee KY, Kim MK, Shin BA, Choi SY. High cleavage efficiency of a 2A peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice.. PLoS One 2011;6(4):e18556.
                    pmc: PMC3084703pubmed: 21602908doi: 10.1371/journal.pone.0018556google scholar: lookup
                  21. Kohli N, Wright KT, Sammons RL, Jeys L, Snow M, Johnson WE. An In Vitro Comparison of the Incorporation, Growth, and Chondrogenic Potential of Human Bone Marrow versus Adipose Tissue Mesenchymal Stem Cells in Clinically Relevant Cell Scaffolds Used for Cartilage Repair.. Cartilage 2015 Oct;6(4):252-63.
                    pmc: PMC4568730pubmed: 26425263doi: 10.1177/1947603515589650google scholar: lookup
                  22. Kumar M, Keller B, Makalou N, Sutton RE. Systematic determination of the packaging limit of lentiviral vectors.. Hum Gene Ther 2001 Oct 10;12(15):1893-905.
                    pubmed: 11589831doi: 10.1089/104303401753153947google scholar: lookup
                  23. Kurth T, Hedbom E, Shintani N, Sugimoto M, Chen FH, Haspl M, Martinovic S, Hunziker EB. Chondrogenic potential of human synovial mesenchymal stem cells in alginate.. Osteoarthritis Cartilage 2007 Oct;15(10):1178-89.
                    pubmed: 17502159doi: 10.1016/j.joca.2007.03.015google scholar: lookup
                  24. Lam J, Lu S, Kasper FK, Mikos AG. Strategies for controlled delivery of biologics for cartilage repair.. Adv Drug Deliv Rev 2015 Apr;84:123-34.
                    pmc: PMC4280354pubmed: 24993610doi: 10.1016/j.addr.2014.06.006google scholar: lookup
                  25. Laurent J, Frongia C, Cazales M, Mondesert O, Ducommun B, Lobjois V. Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D.. BMC Cancer 2013 Feb 8;13:73.
                    pmc: PMC3598667pubmed: 23394599doi: 10.1186/1471-2407-13-73google scholar: lookup
                  26. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.. Methods 2001 Dec;25(4):402-8.
                    pubmed: 11846609doi: 10.1006/meth.2001.1262google scholar: lookup
                  27. Lo Monaco M, Merckx G, Ratajczak J, Gervois P, Hilkens P, Clegg P, Bronckaers A, Vandeweerd JM, Lambrichts I. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures.. Stem Cells Int 2018;2018:9079538.
                    pmc: PMC5832141pubmed: 29535784doi: 10.1155/2018/9079538google scholar: lookup
                  28. Mackay AM, Beck SC, Murphy JM, Barry FP, Chichester CO, Pittenger MF. Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow.. Tissue Eng 1998 Winter;4(4):415-28.
                    pubmed: 9916173doi: 10.1089/ten.1998.4.415google scholar: lookup
                  29. Martín-Peña A, Acebes A, Rodríguez JR, Sorribes A, de Polavieja GG, Fernández-Fúnez P, Ferrús A. Age-independent synaptogenesis by phosphoinositide 3 kinase.. J Neurosci 2006 Oct 4;26(40):10199-208.
                    pmc: PMC6674615pubmed: 17021175doi: 10.1523/jneurosci.1223-06.2006google scholar: lookup
                  30. Matricali GA, Dereymaeker GP, Luyten FP. Donor site morbidity after articular cartilage repair procedures: a review.. Acta Orthop Belg 2010 Oct;76(5):669-74.
                    pubmed: 21138224
                  31. McCarthy HE, Bara JJ, Brakspear K, Singhrao SK, Archer CW. The comparison of equine articular cartilage progenitor cells and bone marrow-derived stromal cells as potential cell sources for cartilage repair in the horse.. Vet J 2012 Jun;192(3):345-51.
                    pubmed: 21968294doi: 10.1016/j.tvjl.2011.08.036google scholar: lookup
                  32. McLeod CM, Mauck RL. On the origin and impact of mesenchymal stem cell heterogeneity: new insights and emerging tools for single cell analysis.. Eur Cell Mater 2017 Oct 27;34:217-231.
                    pmc: PMC7735381pubmed: 29076514doi: 10.22203/ecm.v034a14google scholar: lookup
                  33. Miyamoto C, Matsumoto T, Sakimura K, Shindo H. Osteogenic protein-1 with transforming growth factor-beta1: potent inducer of chondrogenesis of synovial mesenchymal stem cells in vitro.. J Orthop Sci 2007 Nov;12(6):555-61.
                    pubmed: 18040638doi: 10.1007/s00776-007-1176-4google scholar: lookup
                  34. Nathan S, Das De S, Thambyah A, Fen C, Goh J, Lee EH. Cell-based therapy in the repair of osteochondral defects: a novel use for adipose tissue.. Tissue Eng 2003 Aug;9(4):733-44.
                    pubmed: 13678450doi: 10.1089/107632703768247412google scholar: lookup
                  35. Orth P, Madry H. Complex and elementary histological scoring systems for articular cartilage repair.. Histol Histopathol 2015 Aug;30(8):911-9.
                    pubmed: 25876650doi: 10.14670/hh-11-620google scholar: lookup
                  36. Outani H, Okada M, Yamashita A, Nakagawa K, Yoshikawa H, Tsumaki N. Direct induction of chondrogenic cells from human dermal fibroblast culture by defined factors.. PLoS One 2013;8(10):e77365.
                    pmc: PMC3797820pubmed: 24146984doi: 10.1371/journal.pone.0077365google scholar: lookup
                  37. Padmashali RM, Mistriotis P, Liang MS, Andreadis ST. Lentiviral arrays for live-cell dynamic monitoring of gene and pathway activity during stem cell differentiation.. Mol Ther 2014 Nov;22(11):1971-82.
                    pmc: PMC4429726pubmed: 24895998doi: 10.1038/mt.2014.103google scholar: lookup
                  38. Palmer GD, Chao Ph PH, Raia F, Mauck RL, Valhmu WB, Hung CT. Time-dependent aggrecan gene expression of articular chondrocytes in response to hyperosmotic loading.. Osteoarthritis Cartilage 2001 Nov;9(8):761-70.
                    pubmed: 11795996doi: 10.1053/joca.2001.0473google scholar: lookup
                  39. Pei M, Luo J, Chen Q. Enhancing and maintaining chondrogenesis of synovial fibroblasts by cartilage extracellular matrix protein matrilins.. Osteoarthritis Cartilage 2008 Sep;16(9):1110-7.
                    pmc: PMC2596998pubmed: 18282772doi: 10.1016/j.joca.2007.12.011google scholar: lookup
                  40. Porter RM, Liu F, Ferreira E, Lunstord EP, Robichaud K, Evans CH. Characterization of a fluorescence-luminescence reporter construct for extended evaluation of chondrogenesis in vitro and in vivo.. Trans Orthop Res Soc 2012;0559.
                  41. Rey-Rico A, Cucchiarini M. Smart and Controllable rAAV Gene Delivery Carriers in Progenitor Cells for Human Musculoskeletal Regenerative Medicine with a Focus on the Articular Cartilage.. Curr Gene Ther 2017;17(2):127-138.
                    pubmed: 28494738doi: 10.2174/1566523217666170510162459google scholar: lookup
                  42. Roelofs AJ, Rocke JP, De Bari C. Cell-based approaches to joint surface repair: a research perspective.. Osteoarthritis Cartilage 2013 Jul;21(7):892-900.
                    pmc: PMC3694304pubmed: 23598176doi: 10.1016/j.joca.2013.04.008google scholar: lookup
                  43. Roh KH, Nerem RM, Roy K. Biomanufacturing of Therapeutic Cells: State of the Art, Current Challenges, and Future Perspectives.. Annu Rev Chem Biomol Eng 2016 Jun 7;7:455-78.
                    pubmed: 27276552doi: 10.1146/annurev-chembioeng-080615-033559google scholar: lookup
                  44. Sakaguchi Y, Sekiya I, Yagishita K, Muneta T. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source.. Arthritis Rheum 2005 Aug;52(8):2521-9.
                    pubmed: 16052568doi: 10.1002/art.21212google scholar: lookup
                  45. Sharma B, Williams CG, Khan M, Manson P, Elisseeff JH. In vivo chondrogenesis of mesenchymal stem cells in a photopolymerized hydrogel.. Plast Reconstr Surg 2007 Jan;119(1):112-120.
                    pubmed: 17255664doi: 10.1097/01.prs.0000236896.22479.52google scholar: lookup
                  46. Shintani N, Hunziker EB. Chondrogenic differentiation of bovine synovium: bone morphogenetic proteins 2 and 7 and transforming growth factor beta1 induce the formation of different types of cartilaginous tissue.. Arthritis Rheum 2007 Jun;56(6):1869-79.
                    pubmed: 17530715doi: 10.1002/art.22701google scholar: lookup
                  47. Shirasawa S, Sekiya I, Sakaguchi Y, Yagishita K, Ichinose S, Muneta T. In vitro chondrogenesis of human synovium-derived mesenchymal stem cells: optimal condition and comparison with bone marrow-derived cells.. J Cell Biochem 2006 Jan 1;97(1):84-97.
                    pubmed: 16088956doi: 10.1002/jcb.20546google scholar: lookup
                  48. Tanavde V, Vaz C, Rao MS, Vemuri MC, Pochampally RR. Research using Mesenchymal Stem/Stromal Cells: quality metric towards developing a reference material.. Cytotherapy 2015 Sep;17(9):1169-77.
                    pmc: PMC4943322pubmed: 26276001doi: 10.1016/j.jcyt.2015.07.008google scholar: lookup
                  49. Stokes DG, Liu G, Dharmavaram R, Hawkins D, Piera-Velazquez S, Jimenez SA. Regulation of type-II collagen gene expression during human chondrocyte de-differentiation and recovery of chondrocyte-specific phenotype in culture involves Sry-type high-mobility-group box (SOX) transcription factors.. Biochem J 2001 Dec 1;360(Pt 2):461-70.
                    pmc: PMC1222247pubmed: 11716775doi: 10.1042/0264-6021:3600461google scholar: lookup
                  50. Veronesi F, Maglio M, Tschon M, Aldini NN, Fini M. Adipose-derived mesenchymal stem cells for cartilage tissue engineering: state-of-the-art in in vivo studies.. J Biomed Mater Res A 2014 Jul;102(7):2448-66.
                    pubmed: 23894033doi: 10.1002/jbm.a.34896google scholar: lookup
                  51. Vidal MA, Robinson SO, Lopez MJ, Paulsen DB, Borkhsenious O, Johnson JR, Moore RM, Gimble JM. Comparison of chondrogenic potential in equine mesenchymal stromal cells derived from adipose tissue and bone marrow.. Vet Surg 2008 Dec;37(8):713-24.
                    pmc: PMC2746327pubmed: 19121166doi: 10.1111/j.1532-950x.2008.00462.xgoogle scholar: lookup
                  52. Watson RS, Broome TA, Levings PP, Rice BL, Kay JD, Smith AD, Gouze E, Gouze JN, Dacanay EA, Hauswirth WW, Nickerson DM, Dark MJ, Colahan PT, Ghivizzani SC. scAAV-mediated gene transfer of interleukin-1-receptor antagonist to synovium and articular cartilage in large mammalian joints.. Gene Ther 2013 Jun;20(6):670-7.
                    pmc: PMC3577988pubmed: 23151520doi: 10.1038/gt.2012.81google scholar: lookup
                  53. Wickham MQ, Erickson GR, Gimble JM, Vail TP, Guilak F. Multipotent stromal cells derived from the infrapatellar fat pad of the knee.. Clin Orthop Relat Res 2003 Jul;(412):196-212.
                    pubmed: 12838072doi: 10.1097/01.blo.0000072467.53786.cagoogle scholar: lookup
                  54. Williams R, Khan IM, Richardson K, Nelson L, McCarthy HE, Analbelsi T, Singhrao SK, Dowthwaite GP, Jones RE, Baird DM, Lewis H, Roberts S, Shaw HM, Dudhia J, Fairclough J, Briggs T, Archer CW. Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage.. PLoS One 2010 Oct 14;5(10):e13246.
                    pmc: PMC2954799pubmed: 20976230doi: 10.1371/journal.pone.0013246google scholar: lookup
                  55. Yoo JU, Barthel TS, Nishimura K, Solchaga L, Caplan AI, Goldberg VM, Johnstone B. The chondrogenic potential of human bone-marrow-derived mesenchymal progenitor cells.. J Bone Joint Surg Am 1998 Dec;80(12):1745-57.
                    pubmed: 9875932doi: 10.2106/00004623-199812000-00004google scholar: lookup
                  56. Yoshimura H, Muneta T, Nimura A, Yokoyama A, Koga H, Sekiya I. Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle.. Cell Tissue Res 2007 Mar;327(3):449-62.
                    pubmed: 17053900doi: 10.1007/s00441-006-0308-zgoogle scholar: lookup
                  57. Zanoni M, Piccinini F, Arienti C, Zamagni A, Santi S, Polico R, Bevilacqua A, Tesei A. 3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained.. Sci Rep 2016 Jan 11;6:19103.
                    pmc: PMC4707510pubmed: 26752500doi: 10.1038/srep19103google scholar: lookup
                  58. Zhang XY, La Russa VF, Bao L, Kolls J, Schwarzenberger P, Reiser J. Lentiviral vectors for sustained transgene expression in human bone marrow-derived stromal cells.. Mol Ther 2002 May;5(5 Pt 1):555-65.
                    pubmed: 11991746doi: 10.1006/mthe.2002.0585google scholar: lookup
                  59. Zhou G, Lefebvre V, Zhang Z, Eberspaecher H, de Crombrugghe B. Three high mobility group-like sequences within a 48-base pair enhancer of the Col2a1 gene are required for cartilage-specific expression in vivo.. J Biol Chem 1998 Jun 12;273(24):14989-97.
                    pubmed: 9614106doi: 10.1074/jbc.273.24.14989google scholar: lookup

                  Citations

                  This article has been cited 3 times.
                  1. Bianchi A, Velot É, Kempf H, Elkhoury K, Sanchez-Gonzalez L, Linder M, Kahn C, Arab-Tehrany E. Nanoliposomes from Agro-Resources as Promising Delivery Systems for Chondrocytes. Int J Mol Sci 2020 May 13;21(10).
                    doi: 10.3390/ijms21103436pubmed: 32414043google scholar: lookup
                  2. De la Vega RE, Scheu M, Brown LA, Evans CH, Ferreira E, Porter RM. Specific, Sensitive, and Stable Reporting of Human Mesenchymal Stromal Cell Chondrogenesis. Tissue Eng Part C Methods 2019 Mar;25(3):176-190.
                    doi: 10.1089/ten.TEC.2018.0295pubmed: 30727864google scholar: lookup
                  3. Celik B, Rintz E, Khan S, Leal AF, Nidhi F, Tomatsu S. In vivo direct lentiviral gene therapy improves disease pathology in a mucopolysaccharidosis IVA murine model. Mol Ther Methods Clin Dev 2025 Sep 11;33(3):101514.
                    doi: 10.1016/j.omtm.2025.101514pubmed: 40677837google scholar: lookup
                  Subscribe to our newsletter
                  Join 99,727 horse owners like you who receive our email updates on horse health and nutrition.