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Cells2021; 10(11); doi: 10.3390/cells10112972

Macroscopic, Histologic, and Immunomodulatory Response of Limb Wounds Following Intravenous Allogeneic Cord Blood-Derived Multipotent Mesenchymal Stromal Cell Therapy in Horses.

Abstract: Limb wounds are common in horses and often develop complications. Intravenous multipotent mesenchymal stromal cell (MSC) therapy is promising but has risks associated with intravenous administration and unknown potential to improve cutaneous wound healing. The objectives were to determine the clinical safety of administering large numbers of allogeneic cord blood-derived MSCs intravenously, and if therapy causes clinically adverse reactions, accelerates wound closure, improves histologic healing, and alters mRNA expression of common wound cytokines. Wounds were created on the metacarpus of 12 horses. Treatment horses were administered 1.51-2.46 × 108 cells suspended in 50% HypoThermosol FRS, and control horses were administered 50% HypoThermosol FRS alone. Epithelialization, contraction, and wound closure rates were determined using planimetric analysis. Wounds were biopsied and evaluated for histologic healing characteristics and cytokine mRNA expression. Days until wound closure was also determined. The results indicate that 3/6 of treatment horses and 1/6 of control horses experienced minor transient reactions. Treatment did not accelerate wound closure or improve histologic healing. Treatment decreased wound size and decreased all measured cytokines except transforming growth factor-β3. MSC intravenous therapy has the potential to decrease limb wound size; however, further work is needed to understand the clinical relevance of adverse reactions.
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Publication Date: 2021-11-01 PubMed ID: 34831196PubMed Central: PMC8616408DOI: 10.3390/cells10112972Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary
  • 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 assesses the potential of using multipotent mesenchymal stromal cells (MSCs) derived from cord blood, administered intravenously, in treating limb wounds in horses. The results show a potential reduction in wound size, but do not demonstrate improved wound closure or histologic healing. Adverse reactions were also noted, requiring further study.

Study Design and Objectives

  • The research aimed to investigate whether cord blood-derived MSC therapy could enhance healing of limb wounds in horses. This included assessing safety, potential adverse reactions, acceleration of wound closure, histologic healing, and changes in cytokine gene expression.
  • The study involved creating wounds on the metacarpus (part of the front leg) of 12 horses split into two groups: one receiving the MSC therapy, and the other treated with just the carrier solution, HypoThermosol FRS.

Procedure and Outcomes

  • The MSC-treated horses were administered large numbers of allogeneic cord blood-derived MSCs intravenously, while the control horses received only the HypoThermosol FRS.
  • The healing process was monitored regularly: wound closure rates were measured using planimetric analysis, biopsied wound tissue was examined histologically, and cytokine mRNA expression was analyzed.
  • Adverse reactions to the treatment were also recorded and tracked.
  • The study found that three treatment horses and one control horse experienced minor temporary reactions.

Findings and Further Research

  • MSC therapy did not accelerate wound closure or enhance histologic healing.
  • However, the treatment managed to decrease the wound size and reduced the expression of all monitored cytokines, except for transforming growth factor-β3, a molecule involved in cell differentiation and immune response.
  • Despite these encouraging findings, more research needs to be conducted to understand the clinical significance of these effects and to investigate the cause of the observed adverse reactions.

Cite This Article

APA
Mund SJK, MacPhee DJ, Campbell J, Honaramooz A, Wobeser B, Barber SM. (2021). Macroscopic, Histologic, and Immunomodulatory Response of Limb Wounds Following Intravenous Allogeneic Cord Blood-Derived Multipotent Mesenchymal Stromal Cell Therapy in Horses. Cells, 10(11). https://doi.org/10.3390/cells10112972

Publication

Cells
ISSN: 2073-4409
NlmUniqueID: 101600052
Country: Switzerland
Language: English
Volume: 10
Issue: 11

Researcher Affiliations

Mund, Suzanne J K
  • Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
MacPhee, Daniel J
  • Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Campbell, John
  • Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Honaramooz, Ali
  • Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Wobeser, Bruce
  • Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Barber, Spencer M
  • Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.

MeSH Terms

  • Administration, Intravenous
  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Epithelium / pathology
  • Extremities / pathology
  • Female
  • Fetal Blood / cytology
  • Gene Expression Regulation
  • Horses
  • Immunomodulation
  • Mesenchymal Stem Cell Transplantation / veterinary
  • Mesenchymal Stem Cells / cytology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transplantation, Homologous
  • Wound Healing
  • Wounds and Injuries / immunology
  • Wounds and Injuries / pathology

Grant Funding

  • 417817 / Mark and Pat DuMont Equine Orthopedic Fund
  • 417560 / Townsend Equine Health Research Fund
  • 418751 / Townsend Equine Health Research Fund

Conflict of Interest Statement

The authors declare no conflict of interest related to this report. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

References

This article includes 68 references
  1. Theoret C., Wilmink J.M.. Exuberant granulation tissue. In: Theoret C., Schumacher J., editors. Equine Wound Management. John Wiley & Sons, Inc.; Ames, IA, USA: 2017. pp. 369–384.
  2. Wilmink J.M., Stolk P.W.T., Van Weeran P.R., Barneveld A.. Differences in second-intention wound healing between horses and ponies: Macroscopic aspects. Equine Vet. J. 1999;31:53–60.
    doi: 10.1111/j.2042-3306.1999.tb03791.xpubmed: 9952330google scholar: lookup
  3. Celeste C.J., Deschene K., Riley C.B., Theoret C.L.. Regional differences in wound oxygenation during normal healing in an equine model of cutaneous fibroproliferative disorder. Wound Repair Regen. 2011;19:89–97.
    doi: 10.1111/j.1524-475X.2010.00639.xpubmed: 20955347google scholar: lookup
  4. Theoret C.L., Moyana T.N., Barber S.M., Gordon J.R.. Preliminary observations on expression of transforming growth factors β1 and β3 in equine full-thickness skin wounds healing normally or with exuberant granulation tissue. Vet. Surg. 2002;31:266–273.
    doi: 10.1053/jvet.2002.32394pubmed: 11994855google scholar: lookup
  5. Theoret C.. Physiology of wound healing. In: Theoret C., Schumacher J., editors. Equine Wound Management. John Wiley & Sons, Inc.; Ames, IA, USA: 2017. pp. 1–13.
  6. Harper D., Young A., McNaught C.-E.. The physiology of wound healing. Surgery 2014;32:445–450.
    doi: 10.1016/j.mpsur.2014.06.010google scholar: lookup
  7. Monteiro S.O., Lepage O.M., Theoret C.L.. Effects of platelet-rich plasma on the repair of wounds on the distal aspect of the forelimb in horses. Am. J. Vet. Res. 2009;70:277–282.
    doi: 10.2460/ajvr.70.2.277pubmed: 19231962google scholar: lookup
  8. Lepault E., Celeste C., Dore M., Martineau D., Theoret C.. Comparative study on microvascular occlusion and apoptosis in body and limb wounds in the horse. Wound Repair Regen. 2005;13:520–529.
    doi: 10.1111/j.1067-1927.2005.00073.xpubmed: 16176461google scholar: lookup
  9. Theoret C.L., Barber S.M., Moyana T.N., Gordon J.R.. Expression of transforming growth factor β1, β3, and basic fibroblast growth factor in full-thickness skin wounds of equine limbs and thorax. Vet. Surg. 2001;30:269–277.
    doi: 10.1053/jvet.2001.23341pubmed: 11340559google scholar: lookup
  10. Lanci A., Merlo B., Mariella J., Castagnetti C., Iacono E.. Heterologous Wharton′s jelly derived mesenchymal stem cells application on a large chronic skin wound in a 6-month-old filly. Front. Vet. Sci. 2019;6:9.
    doi: 10.3389/fvets.2019.00009pmc: PMC6363668pubmed: 30761313google scholar: lookup
  11. Textor J.A., Clark K.C., Walker N.J., Aristizobal F.A., Kol A., LeJeune S.S., Bledsoe A., Davidyan A., Gray S.N., Bohannon-Worsley L.K.. Allogeneic stem cells alter gene expression and improve healing of distal limb wounds in horses. Stem Cells Transl. Med. 2018;7:98–108.
    doi: 10.1002/sctm.17-0071pmc: PMC5746157pubmed: 29063737google scholar: lookup
  12. Liubaviciute A., Kaseta V., Vaitkuviene A., Mackiewicz Z., Biziuleviciene G.. Regenerative potential of partially differentiated mesenchymal stromal cells in a mouse model of a full-thickness wound. EXCLI J. 2018;17:871–888.
    pmc: PMC6141819pubmed: 30233286
  13. Liu L., Yu Y., Hou Y., Chai J., Duan H., Chu W., Zhang H., Hu Q., Du J.. Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats. PLoS ONE 2014;9:e88348.
    doi: 10.1371/journal.pone.0088348pmc: PMC3930522pubmed: 24586314google scholar: lookup
  14. Rustad K.C., Gurtner G.C.. Mesenchymal stem cells home to sites of injury and inflammation. Adv. Wound Care 2012;1:147–152.
    doi: 10.1089/wound.2011.0314pmc: PMC3623614pubmed: 24527296google scholar: lookup
  15. Maxson S., Lopez E.A., Yoo D., Danilkovitch-Miagkova A., LeRoux M.A.. Concise review: Role of mesenchymal stem cells in wound repair. Stem Cells Transl. Med. 2012;1:142–149.
    doi: 10.5966/sctm.2011-0018pmc: PMC3659685pubmed: 23197761google scholar: lookup
  16. Kean T.J., Lin P., Caplan A.I., Dennis J.E., Kean J.. MSCs: Delivery routes and engraftment, cell-targeting strategies, and immune modulation. Stem Cells Int. 2013;2013:732742.
    doi: 10.1155/2013/732742pmc: PMC3755386pubmed: 24000286google scholar: lookup
  17. De Schauwer C.. Stem cell therapy in the horse: From laboratory to clinic. Vet. J. 2015;203:137.
    doi: 10.1016/j.tvjl.2014.12.033pubmed: 25599901google scholar: lookup
  18. Williams L.B., Tessier L., Koenig J.B., Koch T.G.. Post-thaw non-cultured and post-thaw cultured equine cord blood mesenchymal stromal cells equally suppress lymphocyte proliferation in vitro. PLoS ONE 2014;9:e113615.
    doi: 10.1371/journal.pone.0113615pmc: PMC4249887pubmed: 25438145google scholar: lookup
  19. White S.V., Czisch C.E., Han M.H., Plant C.D., Harvey A.R., Plant G.W.. Intravenous transplantation of mesenchymal progenitors distribute solely to the lungs and improve outcomes in cervical spinal cord injury. Stem Cells 2016;34:1812–1825.
    doi: 10.1002/stem.2364pubmed: 26989838google scholar: lookup
  20. Kol A., Wood J.A., Carrade Holt D.D., Gillette J.A., Bohannon-Worsley L.K., Puchalski S.M., Walker N.J., Clark K.C., Watson J.L., Borjesson D.L.. Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses. Stem Cell Res. Ther. 2015;6:73.
    doi: 10.1186/s13287-015-0050-0pmc: PMC4446064pubmed: 25888916google scholar: lookup
  21. Williams L.B., Co C., Koenig J.B., Tse C., Lindsay E., Koch T.G.. Response to intravenous allogeneic equine cord blood-derived mesenchymal stromal cells administered from chilled or frozen state in serum and protein-free media. Front. Vet. Sci. 2016;3:56.
    doi: 10.3389/fvets.2016.00056pmc: PMC4956649pubmed: 27500136google scholar: lookup
  22. Broeckx S., Borena B.M., Zimmerman M., Marien T., Serys B., Suls M., Duchateau L., Spaas J.H.. Intravenous application of allogeneic peripheral blood-derived mesenchymal stem cells: A safety assessment in 291 equine recipients. Curr. Stem Cell Res. Ther. 2014;9:452–457.
    doi: 10.2174/1574888X09666140220003847pubmed: 24548143google scholar: lookup
  23. Owens S.D., Kol A., Walker N.J., Borjesson D.L.. Allogeneic mesenchymal stem cell treatment induces specific alloantibodies in horses. Stem Cells Int. 2016;2016:5830103.
    doi: 10.1155/2016/5830103pmc: PMC5018342pubmed: 27648075google scholar: lookup
  24. Kanji S., Das H.. Advances of stem cell therapeutics in cutaneous wound healing and regeneration. Mediat. Inflamm. 2017;2017:5217967.
    doi: 10.1155/2017/5217967pmc: PMC5682068pubmed: 29213192google scholar: lookup
  25. Wilmink J.M.. Differences in wound healing between horses and ponies. In: Theoret C., Schumacher J., editors. Equine Wound Management. John Wiley & Sons, Inc.; Ames, IA, USA: 2017. pp. 14–29.
  26. Mund S.J.K., Kawamura E., Awang-Junaidi A.H., Campbell J., Wobeser B., MacPhee D.J., Honaramooz A., Barber S.. Homing and engraftment of intravenously administered equine cord blood-derived multipotent mesenchymal stromal cells to surgically created cutaneous wounds in horses: A pilot project. Cells 2020;9:1162.
    doi: 10.3390/cells9051162pmc: PMC7290349pubmed: 32397125google scholar: lookup
  27. Dart A.J., Perkins N.R., Dart C.M., Jeffcott L.B., Canfield P.. Effect of bandaging on second intention healing of wounds of the distal limb in horses. Aust. Vet. J. 2009;87:215–218.
    doi: 10.1111/j.1751-0813.2009.00428.xpubmed: 19489777google scholar: lookup
  28. Hanson R.R.. Medical Therapy in Equine Wound Management. Vet. Clin. N. Am. Equine Pract. 2018;34:591–603.
    doi: 10.1016/j.cveq.2018.07.008pubmed: 30342803google scholar: lookup
  29. Huss M.K., Felt S.A., Pacharinsak C.. Influence of pain and analgesia on orthopedic and wound-healing models in rats and mice. Comp. Med. 2019;69:535–545.
    doi: 10.30802/AALAS-CM-19-000013pmc: PMC6935707pubmed: 31561753google scholar: lookup
  30. Koch T.G., Thomsen P.D., Betts D.H.. Improved isolation protocol for equine cord blood-derived mesenchymal stromal cells. Cytotherapy 2009;11:443–447.
    doi: 10.1080/14653240902887259pubmed: 19513899google scholar: lookup
  31. Tessier L., Bienzle D., Williams L.B., Koch T.G.. Phenotypic and immunomodulatory properties of equine cord blood-derived mesenchymal stromal cells. PLoS ONE 2015;10:e0122954.
    doi: 10.1371/journal.pone.0122954pmc: PMC4406608pubmed: 25902064google scholar: lookup
  32. Yang Y., Honaramooz A.. Effects of medium and hypothermic temperatures on preservation of isolated porcine testis cells. Reprod. Fertil. Dev. 2010;22:523–532.
    doi: 10.1071/RD09206pubmed: 20188025google scholar: lookup
  33. Correia C., Koshkin A., Carido M., Espinha N., Saric T., Lima P.A., Serra M., Alves P.M.. Effective hypothermic storage of human pluripotent stem cell-derived cardiomyocytes compatible with global distribution of cells for clinical applications and toxicology testing. Stem Cells Transl. Med. 2016;5:658–669.
    doi: 10.5966/sctm.2015-0238pmc: PMC4835249pubmed: 27025693google scholar: lookup
  34. Freitas-Ribeiro S., Carvalho A.F., Costa M., Cerqueira M.T., Marques A.P., Reis R.L., Pirraco R.P.. Strategies for the hypothermic preservation of cell sheets of human adipose stem cells. PLoS ONE 2019;14:e0222597.
    doi: 10.1371/journal.pone.0222597pmc: PMC6793945pubmed: 31613935google scholar: lookup
  35. Petrenko Y., Chudickova M., Vackova I., Groh T., Kosnarova E., Cejkova J., Turnovcova K., Petrenko A., Sykova E., Kubinova S.. Clinically relevant solution for the hypothermic storage and transportation of human multipotent mesenchymal stromal cells. Stem Cells Int. 2019;2019:5909524.
    doi: 10.1155/2019/5909524pmc: PMC6360551pubmed: 30805009google scholar: lookup
  36. Yeh D.D., Nazarian R.M., Demetri L., Mesar T., Dijkink S., Larentzakis A., Velmahos G., Sadik K.W.. Histopathological assessment of OASIS Ultra on critical-sized wound healing: A pilot study. J. Cutan. Pathol. 2017;44:523–529.
    doi: 10.1111/cup.12925pubmed: 28256051google scholar: lookup
  37. Korchunjit W., Laikul A., Taylor J., Watchrarat K., Ritruechai P., Supokawej A., Wongtawan T.. Characterization and allogeneic transplantation of equine bone marrow–derived multipotent mesenchymal stromal cells collected from cadavers. J. Equine Vet. Sci. 2019;73:15–23.
    doi: 10.1016/j.jevs.2018.11.004google scholar: lookup
  38. Kawata Y., Tsuchiya A., Seino S., Watanabe Y., Kojima Y., Ikarashi S., Tominaga K., Yokoyama J., Yamagiwa S., Terai S.. Early injection of human adipose tissue-derived mesenchymal stem cell after inflammation ameliorates dextran sulfate sodium-induced colitis in mice through the induction of M2 macrophages and regulatory T cells. Cell Tissue Res. 2019;376:257–271.
    doi: 10.1007/s00441-018-02981-wpubmed: 30635774google scholar: lookup
  39. Gugjoo M.B., Sharma G.T.. Equine mesenchymal stem cells: Properties, sources, characterization, and potential therapeutic applications. J. Equine Vet. Sci. 2019;72:16–27.
    doi: 10.1016/j.jevs.2018.10.007pubmed: 30929778google scholar: lookup
  40. Huang X.P., Sun Z., Miyagi Y., Kinkaid H.M., Zhang L., Weisel R.D., Li R.K.. Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation 2010;122:2419–2429.
    doi: 10.1161/CIRCULATIONAHA.110.955971pubmed: 21098445google scholar: lookup
  41. Tano N., Kaneko M., Ichihara Y., Ikebe C., Coppen S.R., Shiraishi M., Shintani Y., Yashiro K., Warrens A., Suzuki K.. Allogeneic mesenchymal stromal cells transplanted onto the heart surface achieve therapeutic myocardial repair despite immunologic responses in rats. J. Am. Heart Assoc. 2016;5:e002815.
    doi: 10.1161/JAHA.115.002815pmc: PMC4802488pubmed: 26896478google scholar: lookup
  42. Pigott J.H., Ishihara A., Wellman M.L., Russell D.S., Bertone A.L.. Inflammatory effects of autologous, genetically modified autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses. Vet. Comp. Orthop. Traumatol. 2013;26:453–460.
    pubmed: 24080668
  43. Ankrum J.A., Ong J.F., Karp J.M.. Mesenchymal stem cells: Immune evasive, not immune privileged. Nat. Biotechnol. 2014;32:252–260.
    doi: 10.1038/nbt.2816pmc: PMC4320647pubmed: 24561556google scholar: lookup
  44. Williams L.B., Koenig J.B., Black B., Gibson T.W.G., Sharif S., Koch T.G.. Equine allogeneic umbilical cord blood derived mesenchymal stromal cells reduce synovial fluid nucleated cell count and induce mild self-limiting inflammation when evaluated in an lipopolysaccharide induced synovitis model. Equine Vet. J. 2016;48:619–625.
    doi: 10.1111/evj.12477pubmed: 26114736google scholar: lookup
  45. Barrachina L., Remacha A.R., Romero A., Vitoria A., Albareda J., Prades M., Roca M., Zaragoza P., Vázquez F.J., Rodellar C.. Assessment of effectiveness and safety of repeat administration of proinflammatory primed allogeneic mesenchymal stem cells in an equine model of chemically induced osteoarthritis. BMC Vet. Res. 2018;14:241.
    doi: 10.1186/s12917-018-1556-3pmc: PMC6098603pubmed: 30119668google scholar: lookup
  46. Broeckx S.Y., Seys B., Suls M., Vandenberghe A., Mariën T., Adriaensen E., Declercq J., Van Hecke L., Braun G., Hellmann K.. Equine allogeneic chondrogenic induced mesenchymal stem cells are an effective treatment for degenerative joint disease in horses. Stem Cells Dev. 2019;28:410–422.
    doi: 10.1089/scd.2018.0061pmc: PMC6441287pubmed: 30623737google scholar: lookup
  47. Lutton B.V., Cho P.S., Hirsh E.L., Ferguson K.K., Teague A.G.S., Hanekamp J.S., Chi N., Goldman S.N., Messina D.J., Houser S.. Approaches to avoid immune responses induced by repeated subcutaneous injections of allogeneic umbilical cord tissue-derived cells. Transplantation 2010;90:494–501.
    doi: 10.1097/TP.0b013e3181c6ff73pmc: PMC3740357pubmed: 21451445google scholar: lookup
  48. Furlani D., Ugurlucan M., Ong L., Bieback K., Pittermann E., Westien I., Wang W., Yerebakan C., Li W., Gaebel R.. Is the intravascular administration of mesenchymal stem cells safe? Mesenchymal stem cells and intravital microscopy. Microvasc. Res. 2009;77:370–376.
    doi: 10.1016/j.mvr.2009.02.001pubmed: 19249320google scholar: lookup
  49. Monnet X., Teboul J.L.. Transpulmonary thermodilution: Advantages and limits. Crit. Care 2017;21:147.
    doi: 10.1186/s13054-017-1739-5pmc: PMC5474867pubmed: 28625165google scholar: lookup
  50. Argueta E.E., Paniagua D.. Thermodilution cardiac output: A concept over 250 years in the making. Cardiol. Rev. 2019;27:138–144.
    doi: 10.1097/CRD.0000000000000223pubmed: 30946701google scholar: lookup
  51. Taylor M., Bailes J., Elrifai A., Shih S.-R., Teeple E., Leavitt M., Baust J., Maroon J.. A new solution for life without blood: Asanguineous low-flow perfusion of a whole-body perfusate during 3 hours of cardiac arrest and profound hypothermia. Circulation 1995;91:431–444.
    doi: 10.1161/01.CIR.91.2.431pubmed: 7805248google scholar: lookup
  52. Fielding C.L.. Potassium homeostasis and derangements. In: Fielding C.L., Magdesian K.G., editors. Equine Fluid Therapy. John Wiley & Sons, Inc.; Ames, IA, USA: 2015. pp. 27–44.
  53. Carvalho A.É.S., Sousa M.R.R., Alencar-Silva T., Carvalho J.L., Saldanha-Araujo F.. Mesenchymal stem cells immunomodulation: The road to IFN-γ licensing and the path ahead. Cytokine Growth Factor Rev. 2019;47:32–42.
    doi: 10.1016/j.cytogfr.2019.05.006pubmed: 31129018google scholar: lookup
  54. Kim S.Y., Nair M.G.. Macrophages in wound healing: Activation and plasticity. Immunol. Cell Biol. 2019;97:258–267.
    doi: 10.1111/imcb.12236pmc: PMC6426672pubmed: 30746824google scholar: lookup
  55. Sole A., Spriet M., Galuppo L.D., Padgett K.A., Borjesson D.L., Wisner E.R., Brosnan R.J., Vidal M.A.. Scintigraphic evaluation of intra-arterial and intravenous regional limb perfusion of allogeneic bone marrow-derived mesenchymal stem cells in the normal equine distal limb using (99m) Tc-HMPAO. Equine Vet. J. 2012;44:594–599.
    doi: 10.1111/j.2042-3306.2011.00530.xpubmed: 22212017google scholar: lookup
  56. Sole A., Spriet M., Padgett K.A., Vaughan B., Galuppo L.D., Borjesson D.L., Wisner E.R., Vidal M.A.. Distribution and persistence of technetium-99 hexamethyl propylene amine oxime-labelled bone marrow-derived mesenchymal stem cells in experimentally induced tendon lesions after intratendinous injection and regional perfusion of the equine distal limb. Equine Vet. J. 2013;45:726–731.
    doi: 10.1111/evj.12063pubmed: 23574488google scholar: lookup
  57. Trela J.M., Spriet M., Padgett K.A., Galuppo L.D., Vaughan B., Vidal M.A.. Scintigraphic comparison of intra-arterial injection and distal intravenous regional limb perfusion for administration of mesenchymal stem cells to the equine foot. Equine Vet. J. 2014;46:479–483.
    doi: 10.1111/evj.12137pubmed: 23834199google scholar: lookup
  58. Becerra P., Valdés Vázquez M.A., Dudhia J., Fiske-Jackson A.R., Neves F., Hartman N.G., Smith R.K.W.. Distribution of injected technetium99m-labeled mesenchymal stem cells in horses with naturally occurring tendinopathy. J. Orthop. Res. 2013;31:1096–1102.
    doi: 10.1002/jor.22338pubmed: 23508674google scholar: lookup
  59. Nitzsche F., Müller C., Lukomska B., Jolkkonen J., Deten A., Boltze J.. The MSC adhesion cascade—Insights into homing and transendothelial migration. Stem Cells 2017;35:1446–1460.
    doi: 10.1002/stem.2614pubmed: 28316123google scholar: lookup
  60. Ezquer F.E., Ezquer M.E., Vicencio J.M., Calligaris S.D.. Two complementary strategies to improve cell engraftment in mesenchymal stem cell-based therapy: Increasing transplanted cell resistance and increasing tissue receptivity. Cell Adhes. Migr. 2017;11:110–119.
    doi: 10.1080/19336918.2016.1197480pmc: PMC5308221pubmed: 27294313google scholar: lookup
  61. Guest D.J., Smith M.R.W., Allen W.R.. Equine embryonic stem-like cells and mesenchymal stromal cells have different survival rates and migration patterns following their injection into damaged superficial digital flexor tendon. Equine Vet. J. 2010;42:636–642.
    doi: 10.1111/j.2042-3306.2010.00112.xpubmed: 20840579google scholar: lookup
  62. Carvalho A.M., Yamada A.L.M., Golim M.A., Álvarez L.E.C., Hussni C.A., Alves A.L.G.. Evaluation of mesenchymal stem cell migration after equine tendonitis therapy. Equine Vet. J. 2014;46:635–638.
    doi: 10.1111/evj.12173pubmed: 23998777google scholar: lookup
  63. Spriet M., Trela J.M., Galuppo L.D.. Ultrasound-guided injection of the median artery in the standing sedated horse. Equine Vet. J. 2015;47:245–248.
    doi: 10.1111/evj.12260pubmed: 24612194google scholar: lookup
  64. Xu J., Xiong Y.-Y., Li Q., Hu M.-J., Huang P.-S., Xu J.-Y., Tian X.-Q., Jin C., Liu J.-D., Qian L.. Optimization of timing and times for administration of atorvastatin-oretreated mesenchymal stem cells in a preclinical model of acute myocardial infarction. Stem Cells Transl. Med. 2019;8:1068–1083.
    doi: 10.1002/sctm.19-0013pmc: PMC6766601pubmed: 31245934google scholar: lookup
  65. Othman O.E., Mahrous K.F., Shafey H.I.. Mitochondrial DNA genetic variations among four horse populations in Egypt. J. Genet. Eng. Biotechnol. 2017;15:469–474.
    doi: 10.1016/j.jgeb.2017.06.004pmc: PMC6296616pubmed: 30647688google scholar: lookup
  66. Silva G.M., Vogel C.. Quantifying gene expression: The importance of being subtle. Mol. Syst. Biol. 2016;12:885.
    doi: 10.15252/msb.20167325pmc: PMC5081482pubmed: 27951528google scholar: lookup
  67. Mills M.G., Gallagher E.P.. A targeted gene expression platform allows for rapid analysis of chemical-induced antioxidant mRNA expression in zebrafish larvae. PLoS ONE 2017;12:e0171025.
    doi: 10.1371/journal.pone.0171025pmc: PMC5315391pubmed: 28212397google scholar: lookup
  68. Flagella M., Bui S., Zheng Z., Nguyen C.T., Zhang A., Pastor L., Ma Y., Yang W., Crawford K.L., McMaster G.K.. A multiplex branched DNA assay for parallel quantitative gene expression profiling. Anal. Biochem. 2006;352:50–60.
    doi: 10.1016/j.ab.2006.02.013pubmed: 16545767google scholar: lookup
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