FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Cells2020; 9(5); doi: 10.3390/cells9051162

Homing and Engraftment of Intravenously Administered Equine Cord Blood-Derived Multipotent Mesenchymal Stromal Cells to Surgically Created Cutaneous Wound in Horses: A Pilot Project.

Abstract: Limb wounds on horses are often slow to heal and are prone to developing exuberant granulation tissue (EGT) and close primarily through epithelialization, which results in a cosmetically inferior and non-durable repair. In contrast, wounds on the body heal rapidly and primarily through contraction and rarely develop EGT. Intravenous (IV) multipotent mesenchymal stromal cells (MSCs) are promising. They home and engraft to cutaneous wounds and promote healing in laboratory animals, but this has not been demonstrated in horses. Furthermore, the clinical safety of administering >1.00 × 108 allogeneic MSCs IV to a horse has not been determined. A proof-of-principle pilot project was performed with two horses that were administered 1.02 × 108 fluorescently labeled allogeneic cord blood-derived MSCs (CB-MSCs) following wound creation on the forelimb and thorax. Wounds and contralateral non-wounded skin were sequentially biopsied on days 0, 1, 2, 7, 14, and 33 and evaluated with confocal microscopy to determine presence of homing and engraftment. Results confirmed preferential homing and engraftment to wounds with persistence of CB-MSCs at 33 days following wound creation, without clinically adverse reactions to the infusion. The absence of overt adverse reactions allows further studies to determine effects of IV CB-MSCs on equine wound healing.
Get Full Text
Publication Date: 2020-05-08 PubMed ID: 32397125PubMed Central: PMC7290349DOI: 10.3390/cells9051162Google 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
  • 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 research explores the process and consequence of injecting horses with a specific type of cell derived from cord blood – termed multipotent mesenchymal stromal cells (MSCs) – in efforts to aid the healing of limb wounds. Initial results suggest the cells are drawn to the wound site and remained there for an extended period, with no negative side effects observed.

Horse Wound Healing Challenges

  • Unlike wounds elsewhere on their bodies, wounds on horse limbs certainly develop excess granulation tissue and heal primarily through a process called epithelialization. This provides a cosmetically unattractive result and a repair that is not long-lasting.
  • Rapid healing in horses typically happens through contraction and rarely develops any unwanted issues like excessive granulation.
  • The researchers are interested in a type of cells called MSCs which show promise for efficient wound healing. These cells are known to find their way to the wound sites and help regenerate the damaged tissues in lab animals. However, this process hasn’t been fully tested and confirmed in horses.
  • The safe dosage of these cells, when given through an intravenous (IV) method, is also unknown in horses.

Pilot Study Overview

  • To investigate the potential of these cells in wound healing in horses, the team carried out a small-scale study on two horses with artificial wounds created on their limbs and thorax.
  • They infused more than 1.00 × 10 of the MSCs, derived from cord blood and labelled with a visible marker for easy detection, into the horses.
  • Biopsies were taken from the wounds and the skin not affected by wounds on a schedule. This included day 0 (before treatment), 1, 2, 7, 14, and a month following the wound creation.

Findings and Implications

  • The microscopy evaluation of the biopsied skin tissue samples confirmed the MSCs were able to detect the wound sites and homed in on them more than non-wounded areas.
  • These cells were still identifiable at the wound site a month following the wounds’ creation, suggesting they can maintain their presence for a long time.
  • The horses didn’t exhibit any noticeable harmful effects following the MSCs infusion, making it safe for continued exploration in larger trials.
  • These findings have paved the way for further research in using IV MSCs derived from cord blood to enhance wound healing in horses.

Cite This Article

APA
Mund SJK, Kawamura E, Awang-Junaidi AH, Campbell J, Wobeser B, MacPhee DJ, Honaramooz A, Barber S. (2020). Homing and Engraftment of Intravenously Administered Equine Cord Blood-Derived Multipotent Mesenchymal Stromal Cells to Surgically Created Cutaneous Wound in Horses: A Pilot Project. Cells, 9(5). https://doi.org/10.3390/cells9051162

Publication

Cells
ISSN: 2073-4409
NlmUniqueID: 101600052
Country: Switzerland
Language: English
Volume: 9
Issue: 5

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.
Kawamura, Eiko
  • WCVM Imaging Centre, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Awang-Junaidi, Awang Hazmi
  • 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.
Wobeser, Bruce
  • Department of Veterinary Pathology, 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.
Honaramooz, Ali
  • Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.
Barber, Spencer
  • Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.

MeSH Terms

  • Administration, Intravenous
  • Animals
  • Biopsy
  • Extremities / pathology
  • Fetal Blood / cytology
  • Fluorescence
  • Horses
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology
  • Multipotent Stem Cells / cytology
  • Pilot Projects
  • Skin / pathology
  • Wound Healing
  • Wounds and Injuries / pathology
  • Wounds and Injuries / therapy

Conflict of Interest Statement

The authors declare no conflict of interest. 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 82 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.. 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.
  3. Theoret C.L., Wilmink J.M.. Aberrant wound healing in the horse: Naturally occurring conditions reminiscent of those observed in man.. Wound Rep. Regener. 2013;21:365–371.
    doi: 10.1111/wrr.12018pubmed: 23441750google scholar: lookup
  4. Watt S.M., Pleat J.M.. Stem cells, niches and scaffolds: Applications to burns and wound care.. Adv. Drug Deliv. Rev. 2017;123:82–106.
    doi: 10.1016/j.addr.2017.10.012pubmed: 29106911google scholar: lookup
  5. Lee H.J., Jang Y.J.. Recent understandings of biology, prophylaxis and treatment strategies for hypertrophic scars and keloids.. Int. J. Mol. Sci. 2018;19:711.
    doi: 10.3390/ijms19030711pmc: PMC5877572pubmed: 29498630google scholar: lookup
  6. Fong C.-Y., Biswas A., Subramanian A., Srinivasan A., Choolani M., Bongso A.. Human keloid cell characterization and inhibition of growth with human Wharton’s jelly stem cell extracts.. J. Cell. Biochem. 2014;115:826–838.
    doi: 10.1002/jcb.24724pubmed: 24265231google scholar: lookup
  7. 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
  8. Chen M., Przyborowski M., Berthiaume F.. Stem cells for skin tissue engineering and wound healing.. Crit. Rev. Biomed. Eng. 2009;37:399–421.
    doi: 10.1615/CritRevBiomedEng.v37.i4-5.50pmc: PMC3223487pubmed: 20528733google scholar: lookup
  9. 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
  10. 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;2013:1–13.
    doi: 10.1155/2013/732742pmc: PMC3755386pubmed: 24000286google scholar: lookup
  11. 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
  12. 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
  13. Spaas J.H., Gomiero C., Broeckx S.Y., Van Hecke L., Maccatrozzo L., Martens A., Martinello T., Patruno M.. Wound-healing markers after autologous and allogeneic epithelial-like stem cell treatment.. Cytotherapy. 2016;18:562–569.
    doi: 10.1016/j.jcyt.2016.01.008pubmed: 26971684google scholar: lookup
  14. Broeckx S.Y., Borena B.M., Van Hecke L., Chiers K., Maes S., Guest D.J., Meyer E., Duchateau L., Martens A., Spaas J.H.. Comparison of autologous versus allogeneic epithelial-like stem cell treatment in an in vivo equine skin wound model.. J. Cytother. 2015;17:1434–1446.
    doi: 10.1016/j.jcyt.2015.06.004pubmed: 26212608google scholar: lookup
  15. Ortved K.F.. Regenerative medicine and rehabilitation for tendinous and ligamentous injuries in sport horses.. Vet. Clin. North Am. - Equine Pract. 2018;34:359–373.
    doi: 10.1016/j.cveq.2018.04.012pubmed: 29803299google scholar: lookup
  16. 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
  17. 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
  18. 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
  19. Macrin D., Joseph J.P., Pillai A.A., Devi A.. Eminent sources of adult mesenchymal stem cells and their therapeutic imminence.. Stem Cell Rev. Rep. 2017;13:741–756.
    doi: 10.1007/s12015-017-9759-8pubmed: 28812219google scholar: lookup
  20. 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
  21. 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
  22. 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
  23. Millán-Rivero J.E., Martínez C.M., Romecín P.A., Aznar-Cervantes S.D., Carpes-Ruiz M., Cenis J.L., Moraleda J.M., Atucha N.M., García-Bernal D.. Silk fibroin scaffolds seeded with Wharton’s jelly mesenchymal stem cells enhance re-epithelialization and reduce formation of scar tissue after cutaneous wound healing.. Stem Cell Res. Ther. 2019;10:1–14.
    doi: 10.1186/s13287-019-1229-6pmc: PMC6487033pubmed: 31029166google scholar: lookup
  24. Sasaki M., Abe R., Fujita Y., Ando S., Inokuma D., Shimizu H.. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type.. J. Immunol. 2008;180:2581–2587.
    doi: 10.4049/jimmunol.180.4.2581pubmed: 18250469google scholar: lookup
  25. Wu Y., Wang J., Scott P.G., Tredget E.E.. Bone marrow-derived stem cells in wound healing: A review.. Wound Repair Regen. 2007;15:S18–S26.
    doi: 10.1111/j.1524-475X.2007.00221.xpubmed: 17727462google scholar: lookup
  26. 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
  27. Singer D.D., Singer A.J., Gordon C., Brink P.. The effects of rat mesenchymal stem cells on injury progression in a rat model.. Acad. Emerg. Med. 2013;20:398–402.
    doi: 10.1111/acem.12116pubmed: 23701348google scholar: lookup
  28. 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
  29. Espinosa P., Spriet M., Sole A., Walker N.J., Vaughan B., Galuppo L.D.. Scintigraphic Tracking of Allogeneic Mesenchymal Stem Cells in the Distal Limb After Intra-Arterial Injection in Standing Horses.. Vet. Surg. 2016;45:619–624.
    doi: 10.1111/vsu.12485pubmed: 27246971google scholar: lookup
  30. Spriet M., Trela J.M., Galuppo L.D.. Ultrasound-guided injection of the median artery in the standing sedated horse.. Equine Vet. J. 2014:1–4.
    doi: 10.1111/evj.12260pubmed: 24612194google scholar: lookup
  31. 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
  32. Kang M.H., Park H.M.. Evaluation of adverse reactions in dogs following intravenous mesenchymal stem cell transplantation.. Acta Vet. Scand. 2014;56:16.
    doi: 10.1186/1751-0147-56-16pmc: PMC3994522pubmed: 24655411google scholar: lookup
  33. Cui L.L., Kerkelä E., Bakreen A., Nitzsche F., Andrzejewska A., Nowakowski A., Janowski M., Walczak P., Boltze J., Lukomska B.. The cerebral embolism evoked by intra-arterial delivery of allogeneic bone marrow mesenchymal stem cells in rats is related to cell dose and infusion velocity.. Stem Cell Res. Ther. 2015;6:1–9.
    doi: 10.1186/scrt544pmc: PMC4429328pubmed: 25971703google scholar: lookup
  34. Pezzanite L.M., Fortier L.A., Antczak D.F., Cassano J.M., Brosnahan M.M., Miller D., Schnabel L.V.. Equine allogeneic bone marrow-derived mesenchymal stromal cells elicit antibody responses in vivo.. Stem Cell Res. Ther. 2015;6:1–11.
    doi: 10.1186/s13287-015-0053-xpmc: PMC4414005pubmed: 25889095google scholar: lookup
  35. 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
  36. 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;6:1–9.
    doi: 10.1186/s13287-015-0050-0pmc: PMC4446064pubmed: 25888916google scholar: lookup
  37. 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;2016:1–8.
    doi: 10.1155/2016/5830103pmc: PMC5018342pubmed: 27648075google scholar: lookup
  38. 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;3:1–13.
    doi: 10.3389/fvets.2016.00056pmc: PMC4956649pubmed: 27500136google scholar: lookup
  39. Honaramooz A., Megee S., Zeng W., Destrempes M.M., Overton S.A., Luo J., Galantino-Homer H., Modelski M., Chen F., Blash S.. Adeno-associated virus (AAV)-mediated transduction of male germ line stem cells results in transgene transmission after germ cell transplantation.. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2008;22:374–382.
    doi: 10.1096/fj.07-8935compubmed: 17873102google scholar: lookup
  40. Zeng W., Tang L., Bondareva A., Honaramooz A., Tanco V., Dores C., Megee S., Modelski M., Rodriguez-sosa J.R., Paczkowski M.. Viral transduction of male germline stem cells results in transgene transmission after germ cell transplantation in pigs viral transduction of male germline stem cells results in transgene transmission after germ cell transplantation in pigs.. Biol. Reprod. 2013;88:1–9.
    doi: 10.1095/biolreprod.112.104422pmc: PMC4434942pubmed: 23221397google scholar: lookup
  41. Honaramooz A., Megee S.O., Dobrinski I.. Germ Cell Transplantation in Pigs.. Biol. Reprod. 2002;66:21–28.
    doi: 10.1095/biolreprod66.1.21pubmed: 11751259google scholar: lookup
  42. Honaramooz A., Behboodi E., Blash S., Megee S.O., Dobrinski I.. Germ cell transplantation in goats.. Mol. Reprod. Dev. 2003;64:422–428.
    doi: 10.1002/mrd.10205pubmed: 12589654google scholar: lookup
  43. Theoret C.L., Barber S.M., Gordon J.R.. Temporal localization of immunoreactive transforming growth factor B1 in normal equine skin and full-thickness dermal wounds.. Vet. Surg. 2002;31:274–280.
    doi: 10.1053/jvet.2002.32397pubmed: 11994856google scholar: lookup
  44. Theoret C.L., Moyana T.N., Barber S.M., Gordon J.R.. Preliminary observations on expression of transforming growth factors B1 and B3 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
  45. Theoret C.L., Barber S.M., Moyana T.N., Gordon J.R.. Expression of transforming growth factor B1, B3, 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
  46. Wilmink J.M., Stolk P.W.T., Van Weeran P.R., Barneveld A.. Differences in second-intention wound healing between horses and ponies: Histological aspects.. Equine Vet. J. 1999;31:61–67.
    doi: 10.1111/j.2042-3306.1999.tb03792.xpubmed: 9952331google scholar: lookup
  47. 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
  48. Wilmink J.M., Veenman J.N., Van den Boom R., Rutten V.P.M.G., Niewold T.A., Broekhuisen-Davies J.M., Lees P., Armstrong S., Van Weeren P.R., Barneveld A.. Differences in polymorphonucleocyte function and local inflammatory response between horses and ponies.. Equine Vet. J. 2003;35:561–569.
    doi: 10.2746/042516403775467234pubmed: 14515955google scholar: lookup
  49. Van den Boom R., Wilmink J.M., O’Kane S., Wood J., Ferguson M.W.J.. Transforming growth factor-beta levels during second- intention healing are related to the different course of wound contraction in horses and ponies.. Wound Repair Regen. 2002;10:188–194.
    doi: 10.1046/j.1524-475X.2002.10608.xpubmed: 12100380google scholar: lookup
  50. 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
  51. Theoret C.L., Olutoye O.O., Parnell L.K.S., Hicks J.. Equine exuberant granulation tissue and human keloids: A comparative histopathologic study.. Vet. Surg. 2013;42:783–789.
    doi: 10.1111/j.1532-950X.2013.12055.xpubmed: 24015864google scholar: lookup
  52. Huang C., Murphy G.F., Akaishi S., Ogawa R.. Keloids and hypertrophic scars.. Plast. Reconstr. Surg. Glob. Open. 2013;1:e25.
    doi: 10.1097/GOX.0b013e31829c4597pmc: PMC4173836pubmed: 25289219google scholar: lookup
  53. Shaker S.A., Ayuob N.N., Hajrah N.H.. Cell talk: A phenomenon observed in the keloid scar by immunohistochemical study.. Appl. Immunohistochem. Mol. Morphol. 2011;19:153–159.
    doi: 10.1097/PAI.0b013e3181efa2efpubmed: 20881838google scholar: lookup
  54. Kanji S., Das H.. Advances of stem cell therapeutics in cutaneous wound healing and regeneration.. Mediat. Inflamm. 2017;2017:1–14.
    doi: 10.1155/2017/5217967pmc: PMC5682068pubmed: 29213192google scholar: lookup
  55. 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;6:1–5.
    doi: 10.3389/fvets.2019.00009pmc: PMC6363668pubmed: 30761313google scholar: lookup
  56. Spaas J.H., De Schauwer C., Cornillie P., Meyer E., Van Soom A., Van de Walle G.R.. Culture and characterisation of equine peripheral blood mesenchymal stromal cells.. Vet. J. 2013;195:107–113.
    doi: 10.1016/j.tvjl.2012.05.006pubmed: 22717781google scholar: lookup
  57. Iacono E., Merlo B., Pirrone A., Antonelli C., Brunori L., Romagnoli N.. Effects of mesenchymal stem cells isolated from amniotic fluid and platelet- rich plasma gel on severe decubitus ulcers in a septic neonatal foal.. Res. Vet. Sci. 2012;93:1439–1440.
    doi: 10.1016/j.rvsc.2012.04.008pubmed: 22579411google scholar: lookup
  58. Lopez M.J., Jarazo J.. State of the art: Stem cells in equine regenerative medicine.. Equine Vet. J. 2015;47:145–154.
    doi: 10.1111/evj.12311pubmed: 24957845google scholar: lookup
  59. Paterson Y.Z., Rash N., Garvican E.R., Paillot R., Guest D.J.. Equine mesenchymal stromal cells and embryo-derived stem cells are immune privileged in vitro.. Stem Cell Res. Ther. 2014;5:90.
    doi: 10.1186/scrt479pmc: PMC4247727pubmed: 25080326google scholar: lookup
  60. Ranera B., Lyahyai J., Romero A., Vázquez F.J., Remacha A.R., Bernal M.L., Zaragoza P., Rodellar C., Martín-Burriel I.. Immunophenotype and gene expression profiles of cell surface markers of mesenchymal stem cells derived from equine bone marrow and adipose tissue.. Vet. Immunol. Immunopathol. 2011;144:147–154.
    doi: 10.1016/j.vetimm.2011.06.033pubmed: 21782255google scholar: lookup
  61. 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
  62. Colbath A.C., Dow S.W., Phillips J.N., McIlwraith W.C., Goodrich L.R.. Autologous and allogeneic equine mesenchymal stem cells exhibit equivalent immunomodulatory properties in vitro.. Stem Cells Dev. 2017;26:503–511.
    doi: 10.1089/scd.2016.0266pubmed: 27958776google scholar: lookup
  63. Barrachina L., Remacha A.R., Romero A., Vázquez F.J., Albareda J., Prades M., Ranera B., Zaragoza P., Martin-Burriel I., Rodellar C.. Effect of inflammatory environment on equine bone marrow derived mesenchymal stem cells immunogenicity and immunomodulatory properties.. Vet. Immunol. Immunopathol. 2016;171:57–65.
    doi: 10.1016/j.vetimm.2016.02.007pubmed: 26964718google scholar: lookup
  64. Remacha A.R., Barrachina L., Álvarez-Arguedas S., Ranera B., Romero A., Vazquez F.J., Zaragoza P., Yanez R., Martín-Burriel I., Rodellar C.. Expression of genes involved in immune response and in vitro immunosuppressive effect of equine MSCs.. Vet. Immunol. Immunopathol. 2015;165:107–118.
    doi: 10.1016/j.vetimm.2015.04.004pubmed: 25977164google scholar: lookup
  65. Berglund A.K., Schnabel L.V.. Allogeneic major histocompatibility complex-mismatched equine bone marrow-derived mesenchymal stem cells are targeted for death by cytotoxic anti-major histocompatibility complex antibodies.. Equine Vet. J. 2017;49:539–544.
    doi: 10.1111/evj.12647pmc: PMC5425313pubmed: 27862236google scholar: lookup
  66. Aguiar C., Theoret C., Smith O., Segura M., Lemire P., Smith L.C.. Immune potential of allogeneic equine induced pluripotent stem cells.. Equine Vet. J. 2015;47:708–714.
    doi: 10.1111/evj.12345pubmed: 25196173google scholar: lookup
  67. Joswig A.J., Mitchell A., Cummings K.J., Levine G.J., Gregory C.A., Smith R., Watts A.E.. Repeated intra-articular injection of allogeneic mesenchymal stem cells causes an adverse response compared to autologous cells in the equine model.. Stem Cell Res. Ther. 2017;8:42.
    doi: 10.1186/s13287-017-0503-8pmc: PMC5329965pubmed: 28241885google scholar: lookup
  68. Grigg A., Gibson R., Bardy P., Szer J.. Acute portal vein thrombosis after autologous stem cell transplantation.. Bone Marrow Transplant. 1996;18:949–953.
    pubmed: 8932850
  69. Ra J.C., Shin I.S., Kim S.H., Kang S.K., Kang B.C., Lee H.Y., Kim Y.J., Jo J.Y., Yoon E.J., Choi H.J.. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans.. Stem Cells Dev. 2011;20:1297–1308.
    doi: 10.1089/scd.2010.0466pubmed: 21303266google scholar: lookup
  70. Kim Y., Jo S., Kim W.H., Kweon O.-K.. Antioxidant and anti-inflammatory effects of intravenously injected adipose derived mesenchymal stem cells in dogs with acute spinal cord injury.. Stem Cell Res. Ther. 2015;6:1–10.
    doi: 10.1186/s13287-015-0236-5pmc: PMC4660672pubmed: 26612085google scholar: lookup
  71. Gu L.-H., Zhang T.-T., Li Y., Yan H.-J., Qi H., Li F.-R.. Immunogenicity of allogeneic mesenchymal stem cells transplanted via different routes in diabetic rats.. Cell. Mol. Immunol. 2015:444–455.
    doi: 10.1038/cmi.2014.70pmc: PMC4496541pubmed: 25242276google scholar: lookup
  72. Kabat M., Bobkov I., Kumar S., Grumet M.. Trends in mesenchymal stem cell clinical trials 2004–2018: Is efficacy optimal in a narrow dose range?. Stem Cells Transl. Med. 2020;9:17–27.
    doi: 10.1002/sctm.19-0202pmc: PMC6954709pubmed: 31804767google scholar: lookup
  73. Conway A., Vazin T., Spelke D.P., Rode N.A., Healy K.E., Kane R.S., Schaffer D.V.. Multivalent ligands control stem cell behaviour in vitro and in vivo.. Nat. Nanotechnol. 2013;8:831–838.
    doi: 10.1038/nnano.2013.205pmc: PMC3830932pubmed: 24141540google scholar: lookup
  74. Gattazzo F., Urciuolo A., Bonaldo P.. Extracellular matrix: A dynamic microenvironment for stem cell niche.. Biochim. Biophys. Acta. 2014;1840:2506–2519.
    doi: 10.1016/j.bbagen.2014.01.010pmc: PMC4081568pubmed: 24418517google scholar: lookup
  75. 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
  76. Lin W., Xu L., Zwingenberger S., Gibon E., Goodman S.B., Li G.. Mesenchymal stem cells homing to improve bone healing.. J. Orthop. Transl. 2017;9:19–27.
    doi: 10.1016/j.jot.2017.03.002pmc: PMC5822957pubmed: 29662796google scholar: lookup
  77. 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
  78. Wu Y., Chen L., Scott P.G., Tredget E.E.. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis.. Stem Cells (Dayt. Ohio) 2007;25:2648–2659.
    doi: 10.1634/stemcells.2007-0226pubmed: 17615264google scholar: lookup
  79. Li M., Luo X., Lv X., Liu V., Zhao G., Zhang X., Cao W., Wang R., Wang W.. In vivo human adipose-derived mesenchymal stem cell tracking after intra-articular delivery in a rat osteoarthritis model.. Stem Cell Res. Ther. 2016;7:1–13.
    doi: 10.1186/s13287-016-0420-2pmc: PMC5103374pubmed: 27832815google scholar: lookup
  80. 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
  81. Shin L., Peterson D.A.. Human mesenchymal stem cell grafts enhance normal and impaired wound healing by recruiting existing endogenous tissue stem/progenitor cells.. Stem Cells Transl. Med. 2013;2:33–42.
    doi: 10.5966/sctm.2012-0041pmc: PMC3659748pubmed: 23283490google scholar: lookup
  82. 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

Citations

This article has been cited 9 times.
Subscribe to our newsletter
Join 99,780 horse owners like you who receive our email updates on horse health and nutrition.