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Home / Equine Research Bank / Stem Cells Int / Differentiation of equine mesenchymal stromal cells into cel...
Stem cells international2014; 2014; 891518; doi: 10.1155/2014/891518

Differentiation of equine mesenchymal stromal cells into cells of neural lineage: potential for clinical applications.

Abstract: Mesenchymal stromal cells (MSCs) are able to differentiate into extramesodermal lineages, including neurons. Positive outcomes were obtained after transplantation of neurally induced MSCs in laboratory animals after nerve injury, but this is unknown in horses. Our objectives were to test the ability of equine MSCs to differentiate into cells of neural lineage in vitro, to assess differences in morphology and lineage-specific protein expression, and to investigate if horse age and cell passage number affected the ability to achieve differentiation. Bone marrow-derived MSCs were obtained from young and adult horses. Following demonstration of stemness, MSCs were neurally induced and microscopically assessed at different time points. Results showed that commercially available nitrogen-coated tissue culture plates supported proliferation and differentiation. Morphological changes were immediate and all the cells displayed a neural crest-like cell phenotype. Expression of neural progenitor proteins, was assessed via western blot or immunofluorescence. In our study, MSCs generated from young and middle-aged horses did not show differences in their ability to undergo differentiation. The effect of cell passage number, however, is inconsistent and further experiments are needed. Ongoing work is aimed at transdifferentiating these cells into Schwann cells for transplantation into a peripheral nerve injury model in horses.
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Publication Date: 2014-11-24 PubMed ID: 25506367PubMed Central: PMC4260374DOI: 10.1155/2014/891518Google Scholar: Lookup
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  • Journal Article

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 researchers investigated the ability of horse mesenchymal stromal cells (MSCs) to evolve into neural lineage cells in a laboratory setting. They found that these MSCs could indeed become neuron-like cells, with the promise of future applications in nerve injury treatments.

Focus of the Study

  • The study was aimed at understanding the manipulative capability of equine mesenchymal stromal cells (MSCs) – these are prime cells that can potentially develop into a variety of cell types. More specifically, the researchers wanted to see if these cells could differentiate into neural lineage cells, effectively becoming cells that can play a role in the nervous system.

Methodology

  • MSCs were derived from the bone marrow of both young and adult horses for the experiment. The researchers applied neural inductions on the MSCs and observed them at various points of time.
  • In order to promote proliferation (a process that enables cells to reproduce and create more of their kind) and differentiation (whereby cells transform to take up specific roles), the researchers utilized commercially available nitrogen-coated tissue culture plates.
  • Morphological changes, indications of the cell’s physical transformation and its eventual ability to adjust and take on a designated function, were observed immediately, with all cells showing characteristics similar to neural crest cells.
  • The researchers also examined the expression of neural progenitor proteins, precursors to more mature neural cells, through methods such as Western blot or immunofluorescence.

Findings

  • The research noted that the MSCs derived from both young and middle-aged horses exhibited no differences in their ability to undergo the transformation process. However, the impact of cell passage number, which represents the number of times cells have been removed from their culture and replanted for growth, remained inconsistent. The authors highlighted the need for further research in this area.
  • The long-term goal of the study is to trans-differentiate these MSCs into Schwann cells, a type of cell that envelops nerve fibers in the peripheral nervous system and is vital for nerve function. The trans-differentiated cells could then potentially be implanted into a peripheral nerve injury in horses for treatment.

Cite This Article

APA
Cruz Villagrán C, Amelse L, Neilsen N, Dunlap J, Dhar M. (2014). Differentiation of equine mesenchymal stromal cells into cells of neural lineage: potential for clinical applications. Stem Cells Int, 2014, 891518. https://doi.org/10.1155/2014/891518

Publication

Stem cells international
ISSN: 1687-966X
NlmUniqueID: 101535822
Country: United States
Language: English
Volume: 2014
Pages: 891518
PII: 891518

Researcher Affiliations

Cruz Villagrán, Claudia
  • Department of Comparative and Experimental Medicine, University of Tennessee, Knoxville, TN 37996, USA ; Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, TN 37996, USA.
Amelse, Lisa
  • Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, TN 37996, USA.
Neilsen, Nancy
  • Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, TN 37996, USA.
Dunlap, John
  • Advanced Microscopy and Imaging Center, University of Tennessee, Knoxville, TN 37996, USA.
Dhar, Madhu
  • Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, TN 37996, USA.

References

This article includes 44 references
  1. Campbell WW. Evaluation and management of peripheral nerve injury.. Clin Neurophysiol 2008 Sep;119(9):1951-65.
    doi: 10.1016/j.clinph.2008.03.018pubmed: 18482862google scholar: lookup
  2. Forostyak S, Jendelova P, Sykova E. The role of mesenchymal stromal cells in spinal cord injury, regenerative medicine and possible clinical applications.. Biochimie 2013 Dec;95(12):2257-70.
    doi: 10.1016/j.biochi.2013.08.004pubmed: 23994163google scholar: lookup
  3. Woodhoo A, Alonso MB, Droggiti A, Turmaine M, D'Antonio M, Parkinson DB, Wilton DK, Al-Shawi R, Simons P, Shen J, Guillemot F, Radtke F, Meijer D, Feltri ML, Wrabetz L, Mirsky R, Jessen KR. Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity.. Nat Neurosci 2009 Jul;12(7):839-47.
    doi: 10.1038/nn.2323pmc: PMC2782951pubmed: 19525946google scholar: lookup
  4. Cardozo AJ, Gómez DE, Argibay PF. Neurogenic differentiation of human adipose-derived stem cells: relevance of different signaling molecules, transcription factors, and key marker genes.. Gene 2012 Dec 15;511(2):427-36.
    doi: 10.1016/j.gene.2012.09.038pubmed: 23000064google scholar: lookup
  5. Jessen KR, Mirsky R. The origin and development of glial cells in peripheral nerves.. Nat Rev Neurosci 2005 Sep;6(9):671-82.
    doi: 10.1038/nrn1746pubmed: 16136171google scholar: lookup
  6. Kuffler DP. An assessment of current techniques for inducing axon regeneration and neurological recovery following peripheral nerve trauma.. Prog Neurobiol 2014 May;116:1-12.
    pubmed: 24380784doi: 10.1016/j.pneurobio.2013.12.004google scholar: lookup
  7. Pan Y, Cai S. Current state of the development of mesenchymal stem cells into clinically applicable Schwann cell transplants.. Mol Cell Biochem 2012 Sep;368(1-2):127-35.
    doi: 10.1007/s11010-012-1351-6pubmed: 22782527google scholar: lookup
  8. Ren Z, Wang Y, Peng J, Zhao Q, Lu S. Role of stem cells in the regeneration and repair of peripheral nerves.. Rev Neurosci 2012 Jan 26;23(2):135-43.
    doi: 10.1515/revneuro-2011-0069pubmed: 22499672google scholar: lookup
  9. Schaakxs D, Kalbermatten DF, Raffoul W, Wiberg M, Kingham PJ. Regenerative cell injection in denervated muscle reduces atrophy and enhances recovery following nerve repair.. Muscle Nerve 2013 May;47(5):691-701.
    doi: 10.1002/mus.23662pubmed: 23504573google scholar: lookup
  10. Spejo AB, Carvalho JL, Goes AM, Oliveira AL. Neuroprotective effects of mesenchymal stem cells on spinal motoneurons following ventral root axotomy: synapse stability and axonal regeneration.. Neuroscience 2013 Oct 10;250:715-32.
    doi: 10.1016/j.neuroscience.2013.07.043pubmed: 23896572google scholar: lookup
  11. Keilhoff G, Goihl A, Langnäse K, Fansa H, Wolf G. Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelinating cells.. Eur J Cell Biol 2006 Jan;85(1):11-24.
    doi: 10.1016/j.ejcb.2005.09.021pubmed: 16373171google scholar: lookup
  12. Keilhoff G, Stang F, Goihl A, Wolf G, Fansa H. Transdifferentiated mesenchymal stem cells as alternative therapy in supporting nerve regeneration and myelination.. Cell Mol Neurobiol 2006 Oct-Nov;26(7-8):1235-52.
    doi: 10.1007/s10571-006-9029-9pubmed: 16779672google scholar: lookup
  13. Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons.. J Neurosci Res 2000 Aug 15;61(4):364-70.
    pubmed: 10931522doi: 10.1002/1097-4547(20000815)61:4<364::aid-jnr2>3.0.co;2-cgoogle scholar: lookup
  14. Barnabé GF, Schwindt TT, Calcagnotto ME, Motta FL, Martinez G Jr, de Oliveira AC, Keim LM, D'Almeida V, Mendez-Otero R, Mello LE. Chemically-induced RAT mesenchymal stem cells adopt molecular properties of neuronal-like cells but do not have basic neuronal functional properties.. PLoS One 2009;4(4):e5222.
    doi: 10.1371/journal.pone.0005222pmc: PMC2667250pubmed: 19370156google scholar: lookup
  15. Bossio C, Mastrangelo R, Morini R, Tonna N, Coco S, Verderio C, Matteoli M, Bianco F. A simple method to generate adipose stem cell-derived neurons for screening purposes.. J Mol Neurosci 2013 Oct;51(2):274-81.
    doi: 10.1007/s12031-013-9985-8pubmed: 23468184google scholar: lookup
  16. Gong M, Bi Y, Jiang W, Zhang Y, Chen L, Hou N, Chen J, Li T. Retinoic acid receptor beta mediates all-trans retinoic acid facilitation of mesenchymal stem cells neuronal differentiation.. Int J Biochem Cell Biol 2013 Apr;45(4):866-75.
    doi: 10.1016/j.biocel.2013.01.002pubmed: 23318218google scholar: lookup
  17. Wislet-Gendebien S, Leprince P, Moonen G, Rogister B. Regulation of neural markers nestin and GFAP expression by cultivated bone marrow stromal cells.. J Cell Sci 2003 Aug 15;116(Pt 16):3295-302.
    doi: 10.1242/jcs.00639pubmed: 12840074google scholar: lookup
  18. Muñoz-Elías G, Woodbury D, Black IB. Marrow stromal cells, mitosis, and neuronal differentiation: stem cell and precursor functions.. Stem Cells 2003;21(4):437-48.
    doi: 10.1634/stemcells.21-4-437pubmed: 12832697google scholar: lookup
  19. Himeno T, Kamiya H, Naruse K, Cheng Z, Ito S, Kondo M, Okawa T, Fujiya A, Kato J, Suzuki H, Kito T, Hamada Y, Oiso Y, Isobe K, Nakamura J. Mesenchymal stem cell-like cells derived from mouse induced pluripotent stem cells ameliorate diabetic polyneuropathy in mice.. Biomed Res Int 2013;2013:259187.
    doi: 10.1155/2013/259187pmc: PMC3844199pubmed: 24319678google scholar: lookup
  20. Nishida H, Nakayama M, Tanaka H, Kitamura M, Hatoya S, Sugiura K, Suzuki Y, Ide C, Inaba T. Evaluation of transplantation of autologous bone marrow stromal cells into the cerebrospinal fluid for treatment of chronic spinal cord injury in dogs.. Am J Vet Res 2011 Aug;72(8):1118-23.
    doi: 10.2460/ajvr.72.8.1118pubmed: 21801071google scholar: lookup
  21. Voulgari-Kokota A, Fairless R, Karamita M, Kyrargyri V, Tseveleki V, Evangelidou M, Delorme B, Charbord P, Diem R, Probert L. Mesenchymal stem cells protect CNS neurons against glutamate excitotoxicity by inhibiting glutamate receptor expression and function.. Exp Neurol 2012 Jul;236(1):161-70.
    doi: 10.1016/j.expneurol.2012.04.011pubmed: 22561409google scholar: lookup
  22. Hameed A-T, Ibrahim R, Karim A-J, Zuki A, Azmi T, Ramasamy R. Neurobiological observations of bone mesenchymal stem cells in vitro and in vivo of injured sciatic nerve in rabbit. Journal of Animal and Veterinary Advances 2011;10(6):686–691.
    doi: 10.3923/javaa.2011.686.691google scholar: lookup
  23. Tremp M, Meyer Zu Schwabedissen M, Kappos EA, Engels PE, Fischmann A, Scherberich A, Schaefer DJ, Kalbermatten DF. The regeneration potential after human and autologous stem cell transplantation in a rat sciatic nerve injury model can be monitored by MRI.. Cell Transplant 2015;24(2):203-11.
    doi: 10.3727/096368913X676934pubmed: 24380629google scholar: lookup
  24. Stassart RM, Fledrich R, Velanac V, Brinkmann BG, Schwab MH, Meijer D, Sereda MW, Nave KA. A role for Schwann cell-derived neuregulin-1 in remyelination.. Nat Neurosci 2013 Jan;16(1):48-54.
    doi: 10.1038/nn.3281pubmed: 23222914google scholar: lookup
  25. Carter-Arnold JL, Neilsen NL, Amelse LL, Odoi A, Dhar MS. In vitro analysis of equine, bone marrow-derived mesenchymal stem cells demonstrates differences within age- and gender-matched horses.. Equine Vet J 2014 Sep;46(5):589-95.
    doi: 10.1111/evj.12142pubmed: 23855680google scholar: lookup
  26. Kasashima Y, Ueno T, Tomita A, Goodship AE, Smith RK. Optimisation of bone marrow aspiration from the equine sternum for the safe recovery of mesenchymal stem cells.. Equine Vet J 2011 May;43(3):288-94.
    doi: 10.1111/j.2042-3306.2010.00215.xpubmed: 21492205google scholar: lookup
  27. Arnhold SJ, Goletz I, Klein H, Stumpf G, Beluche LA, Rohde C, Addicks K, Litzke LF. Isolation and characterization of bone marrow-derived equine mesenchymal stem cells.. Am J Vet Res 2007 Oct;68(10):1095-105.
    doi: 10.2460/ajvr.68.10.1095pubmed: 17916017google scholar: lookup
  28. Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains.. Proc Natl Acad Sci U S A 1999 Sep 14;96(19):10711-6.
    doi: 10.1073/pnas.96.19.10711pmc: PMC17948pubmed: 10485891google scholar: lookup
  29. Bossolasco P, Cova L, Calzarossa C, Rimoldi SG, Borsotti C, Deliliers GL, Silani V, Soligo D, Polli E. Neuro-glial differentiation of human bone marrow stem cells in vitro.. Exp Neurol 2005 Jun;193(2):312-25.
    doi: 10.1016/j.expneurol.2004.12.013pubmed: 15869934google scholar: lookup
  30. Hermann A, Liebau S, Gastl R, Fickert S, Habisch HJ, Fiedler J, Schwarz J, Brenner R, Storch A. Comparative analysis of neuroectodermal differentiation capacity of human bone marrow stromal cells using various conversion protocols.. J Neurosci Res 2006 Jun;83(8):1502-14.
    doi: 10.1002/jnr.20840pubmed: 16612831google scholar: lookup
  31. Tremain N, Korkko J, Ibberson D, Kopen GC, DiGirolamo C, Phinney DG. MicroSAGE analysis of 2,353 expressed genes in a single cell-derived colony of undifferentiated human mesenchymal stem cells reveals mRNAs of multiple cell lineages.. Stem Cells 2001;19(5):408-18.
    doi: 10.1634/stemcells.19-5-408pubmed: 11553849google scholar: lookup
  32. Woodbury D, Reynolds K, Black IB. Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis.. J Neurosci Res 2002 Sep 15;69(6):908-17.
    doi: 10.1002/jnr.10365pubmed: 12205683google scholar: lookup
  33. Sanchez-Ramos JR. Neural cells derived from adult bone marrow and umbilical cord blood.. J Neurosci Res 2002 Sep 15;69(6):880-93.
    doi: 10.1002/jnr.10337pubmed: 12205681google scholar: lookup
  34. Hermann A, Gastl R, Liebau S, Popa MO, Fiedler J, Boehm BO, Maisel M, Lerche H, Schwarz J, Brenner R, Storch A. Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells.. J Cell Sci 2004 Sep 1;117(Pt 19):4411-22.
    doi: 10.1242/jcs.01307pubmed: 15304527google scholar: lookup
  35. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells.. Science 1999 Apr 2;284(5411):143-7.
    doi: 10.1126/science.284.5411.143pubmed: 10102814google scholar: lookup
  36. Reynolds BA, Tetzlaff W, Weiss S. A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes.. J Neurosci 1992 Nov;12(11):4565-74.
    pmc: PMC6575989pubmed: 1432110doi: 10.1523/jneurosci.12-11-04565.1992google scholar: lookup
  37. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, Freeman TB, Saporta S, Janssen W, Patel N, Cooper DR, Sanberg PR. Adult bone marrow stromal cells differentiate into neural cells in vitro.. Exp Neurol 2000 Aug;164(2):247-56.
    doi: 10.1006/exnr.2000.7389pubmed: 10915564google scholar: lookup
  38. Choong PF, Mok PL, Cheong SK, Leong CF, Then KY. Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro.. Cytotherapy 2007;9(2):170-83.
    doi: 10.1080/14653240701196829pubmed: 17453969google scholar: lookup
  39. Tondreau T, Lagneaux L, Dejeneffe M, Massy M, Mortier C, Delforge A, Bron D. Bone marrow-derived mesenchymal stem cells already express specific neural proteins before any differentiation.. Differentiation 2004 Sep;72(7):319-26.
    doi: 10.1111/j.1432-0436.2004.07207003.xpubmed: 15554943google scholar: lookup
  40. Foudah D, Monfrini M, Donzelli E, Niada S, Brini AT, Orciani M, Tredici G, Miloso M. Expression of neural markers by undifferentiated mesenchymal-like stem cells from different sources.. J Immunol Res 2014;2014:987678.
    doi: 10.1155/2014/987678pmc: PMC3987801pubmed: 24741639google scholar: lookup
  41. Boulland JL, Mastrangelopoulou M, Boquest AC, Jakobsen R, Noer A, Glover JC, Collas P. Epigenetic regulation of nestin expression during neurogenic differentiation of adipose tissue stem cells.. Stem Cells Dev 2013 Apr 1;22(7):1042-52.
    doi: 10.1089/scd.2012.0560pubmed: 23140086google scholar: lookup
  42. Hyder CL, Isoniemi KO, Torvaldson ES, Eriksson JE. Insights into intermediate filament regulation from development to ageing.. J Cell Sci 2011 May 1;124(Pt 9):1363-72.
    doi: 10.1242/jcs.041244pubmed: 21502133google scholar: lookup
  43. Jin X, Jin X, Jung JE, Beck S, Kim H. Cell surface Nestin is a biomarker for glioma stem cells.. Biochem Biophys Res Commun 2013 Apr 19;433(4):496-501.
    doi: 10.1016/j.bbrc.2013.03.021pubmed: 23524267google scholar: lookup
  44. Michalczyk K, Ziman M. Nestin structure and predicted function in cellular cytoskeletal organisation.. Histol Histopathol 2005 Apr;20(2):665-71.
    pubmed: 15736068doi: 10.14670/hh-20.665google scholar: lookup

Citations

This article has been cited 6 times.
  1. Ferreira LVO, Kamura BDC, Oliveira JPM, Chimenes ND, Carvalho M, Santos LAD, Dias-Melicio LA, Amorim RL, Amorim RM. In Vitro Transdifferentiation Potential of Equine Mesenchymal Stem Cells into Schwann-Like Cells.. Stem Cells Dev 2023 Jul;32(13-14):422-432.
    doi: 10.1089/scd.2022.0274pubmed: 37071193google scholar: lookup
  2. Cequier A, Sanz C, Rodellar C, Barrachina L. The Usefulness of Mesenchymal Stem Cells beyond the Musculoskeletal System in Horses.. Animals (Basel) 2021 Mar 25;11(4).
    doi: 10.3390/ani11040931pubmed: 33805967google scholar: lookup
  3. Jahromi IR, Mehrabani D, Mohammadi A, Seno MM, Dianatpour M, Zare S, Tamadon A. Emergence of signs of neural cells after exposure of bone marrow-derived mesenchymal stem cells to fetal brain extract.. Iran J Basic Med Sci 2017 Mar;20(3):301-307.
    doi: 10.22038/ijbms.2017.8360pubmed: 28392903google scholar: lookup
  4. Cruz Villagrán C, Schumacher J, Donnell R, Dhar MS. A Novel Model for Acute Peripheral Nerve Injury in the Horse and Evaluation of the Effect of Mesenchymal Stromal Cells Applied In Situ on Nerve Regeneration: A Preliminary Study.. Front Vet Sci 2016;3:80.
    doi: 10.3389/fvets.2016.00080pubmed: 27695697google scholar: lookup
  5. Khanabdali R, Saadat A, Fazilah M, Bazli KF, Qazi RE, Khalid RS, Hasan Adli DS, Moghadamtousi SZ, Naeem N, Khan I, Salim A, Shamsuddin SA, Mohan G. Promoting effect of small molecules in cardiomyogenic and neurogenic differentiation of rat bone marrow-derived mesenchymal stem cells.. Drug Des Devel Ther 2016;10:81-91.
    doi: 10.2147/DDDT.S89658pubmed: 26766903google scholar: lookup
  6. Guo SL, Zhang ZY, Xu Y, Zhi YX, Han CJ, Zhou YH, Liu F, Lin HY, Zhang CS. Bone marrow-derived, neural-like cells have the characteristics of neurons to protect the peripheral nerve in microenvironment.. Stem Cells Int 2015;2015:941625.
    doi: 10.1155/2015/941625pubmed: 25861281google scholar: lookup
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