FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Frontiers in veterinary science2023; 10; 1293199; doi: 10.3389/fvets.2023.1293199

Preliminary evaluation of safety and migration of immune activated mesenchymal stromal cells administered by subconjunctival injection for equine recurrent uveitis.

Abstract: Equine recurrent uveitis (ERU), an immune mediated disease characterized by repeated episodes of intra-ocular inflammation, affects 25% of horses in the USA and is the most common cause of glaucoma, cataracts, and blindness. Mesenchymal stromal cells (MSCs) have immunomodulatory properties, which are upregulated by preconditioning with toll-like receptor agonists. The objective was to evaluate safety and migration of TLR-3 agonist polyinosinic, polycytidylic acid (pIC)-activated MSCs injected subconjunctivally in healthy horses prior to clinical application in horses with ERU. We hypothesized that activated allogeneic MSCs injected subconjunctivally would not induce ocular or systemic inflammation and would remain in the conjunctiva for >14 days. Unassigned: Bulbar subconjunctiva of two horses was injected with 10 × 106 pIC-activated (10 μg/mL, 2 h) GFP-labeled MSCs from one donor three times at two-week intervals. Vehicle (saline) control was injected in the contralateral conjunctiva. Horses received physical and ophthalmic exams [slit lamp biomicroscopy, rebound tonometry, fundic examination, and semiquantitative preclinical ocular toxicology scoring (SPOTS)] every 1-3 days. Systemic inflammation was assessed via CBC, fibrinogen, and serum amyloid A (SAA). Horses were euthanized 14 days following final injection. Full necropsy and histopathology were performed to examine ocular tissues and 36 systemic organs for MSC presence via IVIS Spectrum. Anti-GFP immunohistochemistry was performed on ocular tissues. Unassigned: No change in physical examinations was noted. Bloodwork revealed fibrinogen 100-300 mg/dL (ref 100-400) and SAA 0-25 μg/mL (ref 0-20). Ocular effects of the subjconjucntival injection were similar between MSC and control eyes on SPOTS grading system, with conjunctival hypermia, chemosis and ocular discharge noted bilaterally, which improved without intervention within 14 days. All other ocular parameters were unaffected throughout the study. Necropsy and histopathology revealed no evidence of systemic inflammation. Ocular histopathology was similar between MSC and control eyes. Fluorescent imaging analysis did not locate MSCs. Immunohistochemistry did not identify intact MSCs in the conjunctiva, but GFP-labeled cellular components were present in conjunctival phagocytic cells. Unassigned: Allogeneic pIC-activated conjunctival MSC injections were well tolerated. GFP-labeled tracking identified MSC components phagocytosed by immune cells subconjunctivally. This preliminary safety and tracking information is critical towards advancing immune conditioned cellular therapies to clinical trials in horses.
Copyright © 2023 Cassano, Leonard, Martins, Vapniarsky, Morgan, Dow, Wotman and Pezzanite.
Get Full Text
Publication Date: 2023-12-14 PubMed ID: 38162475PubMed Central: PMC10757620DOI: 10.3389/fvets.2023.1293199Google 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

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 study investigates the safety and effectiveness of administering immune activated mesenchymal stromal cells (MSCs) via subconjunctival injection to potentially treat equine recurrent uveitis (ERU), a common horse disease affecting eyesight.

Background

  • The primary focus of the research was equine recurrent uveitis (ERU), a disease that affects horses and causes repeated bouts of intra-ocular inflammation. This disease is a significant concern, given its prevalence, as it impacts approximately one in every four horses in the USA.
  • The disease is the most frequent cause of certain eye conditions in horses, such as glaucoma, cataracts, and blindness.
  • The research focused on the use of mesenchymal stromal cells (MSCs), which have immunomodulatory properties. Their application in treating ERU was considered, based on their upregulated properties when preconditioned with toll-like receptor (TLR) agonists.

Study Design

  • The researchers injected TLR-3 agonist polyinosinic, polycytidylic acid (pIC)-activated MSCs subconjunctivally, or under the conjunctiva, in healthy horses to understand the potential reactions before being used with horses already affected by ERU.
  • The study surmised that activated MSCs would not trigger inflammation either around the eyes or systemically, and they would remain in the conjunctiva for more than 14 days.
  • The scientists injected pIC-activated MSCs, marked with a green fluorescent protein (GFP) label, into the conjunctiva of two healthy horses at intervals of two weeks, three times. The other eye was injected with a control saline solution for comparison.
  • Regular physical and ophthalmic exams were conducted post-procedure every 1-3 days. Systemic inflammation was assessed via complete blood count (CBC), fibrinogen levels, and the presence of serum amyloid A (SAA).
  • Post the final injection (after 14 days), the horses were euthanized and a full necropsy and histopathology examination were conducted to look for systemic inflammation and evidence of MSC presence.

Results

  • The study didn’t observe any changes in the horses’ physical condition. The fibrinogen and SAA levels, significant indicators of systemic inflammation, remained within normal range.
  • No significant differences were noted in the ophthalmic assessments of eyes injected with MSCs compared to the control eyes.
  • Also, necropsy and histopathology revealed no signs of systemic inflammation or presence of MSCs.
  • The conducted examinations showed that MSC parts were present within the phagocytic cells in the conjunctiva, indicating that the immune system had ingested these cells.

Conclusion

  • This research concluded that the administration of pIC-activated MSCs via subconjunctival injection was well-tolerated by the horses in the study.
  • The study provided critical preliminary data on the safety and tracking of MSCs, prerequisites for advancing to clinical trials in treating ERU in horses.

Cite This Article

APA
Cassano JM, Leonard BC, Martins BC, Vapniarsky N, Morgan JT, Dow SW, Wotman KL, Pezzanite LM. (2023). Preliminary evaluation of safety and migration of immune activated mesenchymal stromal cells administered by subconjunctival injection for equine recurrent uveitis. Front Vet Sci, 10, 1293199. https://doi.org/10.3389/fvets.2023.1293199

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 10
Pages: 1293199

Researcher Affiliations

Cassano, Jennifer M
  • Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
  • Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
Leonard, Brian C
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
  • Department of Ophthalmology & Vision Science, School of Medicine, University of California, Davis, Davis, CA, United States.
Martins, Bianca C
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
Vapniarsky, Natalia
  • Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
  • Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
Morgan, Joshua T
  • Department of Bioengineering, University of California, Riverside, Riverside, CA, United States.
Dow, Steven W
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
  • Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
Wotman, Kathryn L
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
Pezzanite, Lynn M
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 68 references
  1. Gilger BC. Equine recurrent uveitis: the viewpoint from the USA.. Equine Vet J (2010) 42:57–61.
    doi: 10.1111/j.2042-3306.2010.tb05636.xpubmed: 20939168google scholar: lookup
  2. Gerding JC, Gilger BC. Prognosis and impact of equine recurrent uveitis.. Equine Vet J (2016) 48:290–8.
    doi: 10.1111/evj.12451pubmed: 25891653google scholar: lookup
  3. Curto EM, Gemensky-Metzler AJ, Chandler HL, Wilkie DA. Equine glaucoma: a histopathologic retrospective study (1999-2012).. Vet Ophthalmol (2014) 17:334–42.
    doi: 10.1111/vop.12080pubmed: 23859597google scholar: lookup
  4. Annear MJ, Wilkie DA, Gemensky-Metzler AJ. Semiconductor diode laser transscleral cyclophotocoagulation for the treatment of glaucoma in horses: a retrospective study of 42 eyes.. Vet Ophthalmol (2010) 13:204–9.
    doi: 10.1111/j.1463-5224.2010.00779.xpubmed: 20500721google scholar: lookup
  5. Allbaugh RA. Equine recurrent uveitis: a review of clinical assessment and management.. Equine Vet Educ (2017) 29:279–88.
    doi: 10.1111/eve.12548google scholar: lookup
  6. Saldinger LK, Nelson SG, Bellone RR, Lassaline M, Mack M, Walker NJ. Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro.. Vet Ophthalmol (2019) 23:160–70.
    doi: 10.1111/vop.12704pmc: PMC6980227pubmed: 31441218google scholar: lookup
  7. Regan DP, Aarnio MC, Davis WS, Carmichael KP, Vandenplas ML, Lauderdale JD. Characterization of cytokines associated with Th17 cells in the eyes of horses with recurrent uveitis.. Vet Ophthalmol (2012) 15:145–52.
    doi: 10.1111/j.1463-5224.2011.00951.xpubmed: 22051225google scholar: lookup
  8. Deeg CA, Amann B, Raith AJ, Kaspers B. Inter- and intramolecular epitope spreading in equine recurrent uveitis.. Investig Ophthalmol Vis Sci (2006) 47:652–6.
    doi: 10.1167/iovs.05-0789pubmed: 16431964google scholar: lookup
  9. Rockwell H, Mack M, Famula T, Sandmeyer L, Bauer B, Dwyer A. Genetic investigation of equine recurrent uveitis in appaloosa horses.. Anim Genet (2020) 51:111–6.
    doi: 10.1111/age.12883pubmed: 31793009google scholar: lookup
  10. Hack Y, Pihl TH, Nielsen RK, Dwyer AE, Bellone RR. A genetic investigation of equine recurrent uveitis in the Icelandic horse breed.. Anim Genet (2022) 53:436–40.
    doi: 10.1111/age.13200pubmed: 35451153google scholar: lookup
  11. Malalana F, Blundell RJ, Pinchbeck GL, Mcgowan CM. The role of Leptospira spp. in horses affected with recurrent uveitis in the UK.. Equine Vet J (2017) 49:706–9.
    doi: 10.1111/evj.12683pmc: PMC5655720pubmed: 28321895google scholar: lookup
  12. Gilger BC, Salmon JH, Yi NY, Barden CA, Chandler HL, Wendt JA. Role of bacteria in the pathogenesis of recurrent uveitis in horses from the southeastern United States.. Am J Vet Res (2008) 69:1329–35.
    doi: 10.2460/ajvr.69.10.1329pubmed: 18828691google scholar: lookup
  13. Cassano JM, Schnabel LV, Betancourt AM, Antczak DF, Fortier LA. Mesenchymal stem cell therapy: clinical Progress and opportunities for advancement.. Curr Pathobiol Rep (2015) 3:1–7.
    doi: 10.1007/s40139-015-0064-4google scholar: lookup
  14. De Schauwer C, Van de Walle GR, Van Soom A, Meyer E. Mesenchymal stem cell therapy in horses: useful beyond orthopedic injuries?. Vet Q (2013) 33:234–41.
    doi: 10.1080/01652176.2013.800250pubmed: 23697553google scholar: lookup
  15. MacDonald ES, Barrett JG. The potential of mesenchymal stem cells to treat systemic inflammation in horses.. Front Vet Sci (2020) 6:1–14.
    doi: 10.3389/fvets.2019.00507pmc: PMC6985200pubmed: 32039250google scholar: lookup
  16. Taylor SD, Serpa PBS, Santos AP, Hart KA, Vaughn SA, Moore GE. Effects of intravenous administration of peripheral blood-derived mesenchymal stromal cells after infusion of lipopolysaccharide in horses.. J Vet Intern Med (2022) 36:1491–501.
    doi: 10.1111/jvim.16447pmc: PMC9308407pubmed: 35698909google scholar: lookup
  17. Watts AE, Yeager AE, Kopyov OV, Nixon AJ. Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model.. Stem Cell Res Ther (2011) 2:4.
    doi: 10.1186/scrt45pmc: PMC3092144pubmed: 21272343google scholar: lookup
  18. 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) 46:589–95.
    doi: 10.1111/evj.12142pubmed: 23855680google scholar: lookup
  19. Baxter MA, Wynn RF, Jowitt SN, Wraith JE, Fairbairn LJ, Bellantuono I. Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion.. Stem Cells (2004) 22:675–82.
    doi: 10.1634/stemcells.22-5-675pubmed: 15342932google scholar: lookup
  20. Pate DO, Clode AB, Olivry T, Cullen JM, Salmon JH, Gilger BC. Immunohistochemical and immunopathologic characterization of superficial stromal immune-mediated keratitis in horses.. Am J Vet Res (2012) 73:1067–73.
    doi: 10.2460/ajvr.73.7.1067pubmed: 22738059google scholar: lookup
  21. Matthews A, Gilger BC. Equine immune-mediated keratopathies.. Vet Ophthalmol (2009) 12:10–6.
    doi: 10.1111/j.1463-5224.2009.00740.xpubmed: 19891646google scholar: lookup
  22. Gilger BC, Michau TM, Salmon JH. Immune-mediated keratitis in horses: 19 cases (1998-2004).. Vet Ophthalmol (2005) 8:233–9.
    doi: 10.1111/j.1463-5224.2005.00393.xpubmed: 16008702google scholar: lookup
  23. Davis AB, Schnabel LV, Gilger BC. Subconjunctival bone marrow-derived mesenchymal stem cell therapy as a novel treatment alternative for equine immune-mediated keratitis: a case series.. Vet Ophthalmol (2019) 22:674–82.
    doi: 10.1111/vop.12641pubmed: 30715781google scholar: lookup
  24. Sherman AB, Gilger BC, Berglund AK, Schnabel LV. Effect of bone marrow-derived mesenchymal stem cells and stem cell supernatant on equine corneal wound healing in vitro.. Stem Cell Res Ther (2017) 8:120.
    doi: 10.1186/s13287-017-0577-3pmc: PMC5445363pubmed: 28545510google scholar: lookup
  25. Carrade DD, Lame MW, Kent MS, Clark KC, Walker NJ, Borjesson DL. Comparative analysis of the immunomodulatory properties of equine adult-derived mesenchymal stem cells().. Cell Med (2012) 4:1–12.
    doi: 10.3727/215517912X647217pmc: PMC3495591pubmed: 23152950google scholar: lookup
  26. Caffi V, Espinosa G, Gajardo G, Morales N, Durán MC, Uberti B. Pre-conditioning of equine bone marrow-derived mesenchymal stromal cells increases their immunomodulatory capacity.. Front Vet Sci (2020) 7:1–13.
    doi: 10.3389/fvets.2020.00318pmc: PMC7325884pubmed: 32656251google scholar: lookup
  27. Gao F, Chiu SM, Motan DAL, Zhang Z, Chen L, Ji HL. Mesenchymal stem cells and immunomodulation: current status and future prospects.. Cell Death Dis (2016) 7:e2062.
    doi: 10.1038/cddis.2015.327pmc: PMC4816164pubmed: 26794657google scholar: lookup
  28. Cassano JM, Schnabel LV, Goodale MB, Fortier LA. Inflammatory licensed equine MSCs are chondroprotective and exhibit enhanced immunomodulation in an inflammatory environment.. Stem Cell Res Ther (2018) 9:82.
    doi: 10.1186/s13287-018-0840-2pmc: PMC5883371pubmed: 29615127google scholar: lookup
  29. Cassano JM, Schnabel LV, Goodale MB, Fortier LA. The immunomodulatory function of equine MSCs is enhanced by priming through an inflammatory microenvironment or TLR3 ligand.. Vet Immunol Immunopathol (2017) 195:33–9.
    doi: 10.1016/j.vetimm.2017.10.003pubmed: 29249315google scholar: lookup
  30. Krampera M. Mesenchymal stromal cell “licensing”: a multistep process.. Leuk Off J Leuk Soc Am Leuk Res Fund UK (2011) 25:1408–14.
    doi: 10.1038/leu.2011.108pubmed: 21617697google scholar: lookup
  31. Waterman RS, Henkle SL, Betancourt AM. Mesenchymal stem cell 1 (MSC1)-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis.. PLoS One (2012) 7:e45590.
    doi: 10.1371/journal.pone.0045590pmc: PMC3447765pubmed: 23029122google scholar: lookup
  32. Delarosa O, Dalemans W, Lombardo E. Toll-like receptors as modulators of mesenchymal stem cells.. Front Immunol (2012) 3:182.
    doi: 10.3389/fimmu.2012.00182pmc: PMC3387651pubmed: 22783256google scholar: lookup
  33. Lombardo E, Delarosa O. Modulation of adult mesenchymal stem cells activity by toll-like receptors: implications on therapeutic potential.. Mediat Inflamm (2010) 2010:865601.
    doi: 10.1155/2010/865601pmc: PMC2902124pubmed: 20628526google scholar: lookup
  34. Johnson V, Webb T, Norman A, Coy J, Kurihara J, Regan D. Activated mesenchymal stem cells interact with antibiotics and host innate immune responses to control chronic bacterial infections.. Sci Rep (2017) 7:9575.
    doi: 10.1038/s41598-017-08311-4pmc: PMC5575141pubmed: 28851894google scholar: lookup
  35. Vidal MA, Walker NJ, Napoli E, Borjesson DL. Evaluation of senescence in mesenchymal stem cells isolated from equine bone marrow, adipose tissue, and umbilical cord tissue.. Stem Cells Dev (2012) 21:273–83.
    doi: 10.1089/scd.2010.0589pubmed: 21410356google scholar: lookup
  36. Barberini DJ, Aleman M, Aristizabal F, Spriet M, Clark KC, Walker NJ. Safety and tracking of intrathecal allogeneic mesenchymal stem cell transplantation in healthy and diseased horses.. Stem Cell Res Ther (2018) 9:96.
    doi: 10.1186/s13287-018-0849-6pmc: PMC5891950pubmed: 29631634google scholar: lookup
  37. Joswig AJ, Mitchell A, Cummings KJ, Levine GJ, Gregory CA, Smith R III. 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
  38. Bernardino PN, Smith WA, Galuppo LD, Mur PE, Cassano JM. Therapeutics prior to mesenchymal stromal cell therapy improves outcome in equine orthopedic injuries.. Am J Vet Res (2022) 83:ajvr.22.04.0072.
    doi: 10.2460/ajvr.22.04.0072pubmed: 35973004google scholar: lookup
  39. Wood JA, Chung DJ, Park SA, Zwingenberger AL, Reilly CM, Ly I. Periocular and intra-articular injection of canine adipose-derived mesenchymal stem cells: an in vivo imaging and migration study.. J Ocul Pharmacol Ther (2012) 28:307–17.
    doi: 10.1089/jop.2011.0166pmc: PMC3361184pubmed: 22175793google scholar: lookup
  40. Ferris DJ, Frisbie DD, Kisiday JD, McIlwraith CW, Hague BA, Major MD. Clinical outcome after intra-articular administration of bone marrow derived mesenchymal stem cells in 33 horses with stifle injury.. Vet Surg (2014) 43:255–65.
    doi: 10.1111/j.1532-950X.2014.12100.xpubmed: 24433318google scholar: lookup
  41. Long A, Nolen-Walston R. Equine inflammatory markers in the twenty-first century: a focus on serum amyloid a.. Vet Clin North Am Equine Pract (2020) 36:147–60.
    doi: 10.1016/j.cveq.2019.12.005pmc: PMC7135104pubmed: 32007299google scholar: lookup
  42. Eaton JS, Miller PE, Bentley E, Thomasy SM, Murphy CJ. The SPOTS system: an ocular scoring system optimized for use in modern preclinical drug development and toxicology.. J Ocul Pharmacol Ther (2017) 33:718–34.
    doi: 10.1089/jop.2017.0108pubmed: 29239680google scholar: lookup
  43. Lim CC, Reilly CM, Thomasy SM, Kass PH, Maggs DJ. Effects of feline herpesvirus type 1 on tear film break-up time, Schirmer tear test results, and conjunctival goblet cell density in experimentally infected cats.. Am J Vet Res (2009) 70:394–403.
    doi: 10.2460/ajvr.70.3.394pubmed: 19254153google scholar: lookup
  44. Thomasy SM, Lim CC, Reilly CM, Kass PH, Lappin MR, Maggs DJ. Evaluation of orally administered famciclovir in cats experimentally infected with feline herpesvirus type-1.. Am J Vet Res (2011) 72:85–95.
    doi: 10.2460/ajvr.72.1.85pubmed: 21194340google scholar: lookup
  45. Zarychta-Wiśniewska W, Burdzinska A, Zagozdzon R, Dybowski B, Butrym M, Gajewski Z. In vivo imaging system for explants analysis—a new approach for assessment of cell transplantation effects in large animal models.. PLoS One (2017) 12:e0184588–21.
    doi: 10.1371/journal.pone.0184588pmc: PMC5607129pubmed: 28931067google scholar: lookup
  46. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T. Fiji: an open-source platform for biological-image analysis.. Nat Methods (2012) 9:676–82.
    doi: 10.1038/nmeth.2019pmc: PMC3855844pubmed: 22743772google scholar: lookup
  47. Angeluci GC, Ricci CL, Passareli JVGC, Estanho GJG, Oliveira AS, Santos SGA. Comparison of four tonometers in the measurement of intraocular pressure in healthy horses.. Equine Vet J (2022) 55:1104–11.
    doi: 10.1111/evj.13911pubmed: 36537844google scholar: lookup
  48. Xu Y, Liu X, Li Y, Dou H, Liang H, Hou Y. SPION-MSCs enhance therapeutic efficacy in sepsis by regulating MSC-expressed TRAF1-dependent macrophage polarization.. Stem Cell Res Ther (2021) 12:531–20.
    doi: 10.1186/s13287-021-02593-2pmc: PMC8501658pubmed: 34627385google scholar: lookup
  49. Voga M, Adamic N, Vengust M, Majdic G. Stem cells in veterinary medicine—current state and treatment options.. Front Vet Sci (2020) 7:1–20.
    doi: 10.3389/fvets.2020.00278pmc: PMC7326035pubmed: 32656249google scholar: lookup
  50. Schnabel LV, Fortier L, CW MI, Nobert KM. Therapeutic use of stem cells in horses: which type, how, and when?. Vet J (2013) 197:570–7.
    doi: 10.1016/j.tvjl.2013.04.018pubmed: 23778257google scholar: lookup
  51. Magri C, Schramme M, Febre M, Cauvin E, Labadie F, Saulnier N. Comparison of efficacy and safety of single versus repeated intra-articular injection of allogeneic neonatal mesenchymal stem cells for treatment of osteoarthritis of the metacarpophalangeal/metatarsophalangeal joint in horses: a clinical pilot study.. PLoS One (2019) 14:e0221317.
    doi: 10.1371/journal.pone.0221317pmc: PMC6715221pubmed: 31465445google scholar: lookup
  52. Schnabel LV, Pezzanite LM, Antczak DF, Felippe MJ, Fortier LA. Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in MHC class II expression and capable of inciting an immune response in vitro.. Stem Cell Res Ther (2014) 5:13.
    doi: 10.1186/scrt402pmc: PMC4055004pubmed: 24461709google scholar: lookup
  53. Pezzanite LM, Fortier LA, Antczak DF, Cassano JM, Brosnahan MM, Miller D. Equine allogeneic bone marrow-derived mesenchymal stromal cells elicit antibody responses in vivo.. Stem Cell Res Ther (2015) 6:54.
    doi: 10.1186/s13287-015-0053-xpmc: PMC4414005pubmed: 25889095google scholar: lookup
  54. Peister A, Mellad J, Larson BL, Hall BM, Gibson LF, Prockop DJ. Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential.. Blood (2004) 103:1662–8.
    doi: 10.1182/blood-2003-09-3070pubmed: 14592819google scholar: lookup
  55. Chow L, Johnson V, Impastato R, Coy J, Strumpf A, Dow S. Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells.. Stem Cells Transl Med (2020) 9:235–49.
    doi: 10.1002/sctm.19-0092pmc: PMC6988770pubmed: 31702119google scholar: lookup
  56. Pezzanite LM, Chow L, Phillips J, Griffenhagen GM, Moore AR, Schaer TP. TLR-activated mesenchymal stromal cell therapy and antibiotics to treat multi-drug resistant staphylococcal septic arthritis in an equine model.. Ann Transl Med (2022) 10:1157–7.
    doi: 10.21037/atm-22-1746pmc: PMC9708491pubmed: 36467344google scholar: lookup
  57. Pezzanite LM, Chow L, Strumpf A, Johnson V, Dow SW. Immune activated cellular therapy for drug resistant infections: rationale, mechanisms, and implications for veterinary medicine.. Vet Sci (2022) 9:610.
    doi: 10.3390/vetsci9110610pmc: PMC9695672pubmed: 36356087google scholar: lookup
  58. Pezzanite LM, Chow L, Johnson V, Griffenhagen GM, Goodrich L, Dow S. Toll-like receptor activation of equine mesenchymal stromal cells to enhance antibacterial activity and immunomodulatory cytokine secretion.. Vet Surg (2021) 50:858–71.
    doi: 10.1111/vsu.13628pubmed: 33797775google scholar: lookup
  59. Chow L, Johnson V, Coy J, Regan D, Dow S. Mechanisms of immune suppression utilized by canine adipose and bone marrow-derived mesenchymal stem cells.. Stem Cells Dev (2017) 26:374–89.
    doi: 10.1089/scd.2016.0207pmc: PMC5327053pubmed: 27881051google scholar: lookup
  60. Johnson V, Chow L, Harrison J, Soontararak S, Dow S. Activated mesenchymal stromal cell therapy for treatment of multi-drug resistant bacterial infections in dogs.. Front Vet Sci (2022) 9:925701.
    doi: 10.3389/fvets.2022.925701pmc: PMC9260693pubmed: 35812842google scholar: lookup
  61. Quintavalla J, Uziel-Fusi S, Yin J, Boehnlein E, Pastor G, Blancuzzi V. Fluorescently labeled mesenchymal stem cells (MSCs) maintain multilineage potential and can be detected following implantation into articular cartilage defects.. Biomaterials (2002) 23:109–19.
    doi: 10.1016/s0142-9612(01)00086-2pubmed: 11762829google scholar: lookup
  62. Guest DJ, Smith MRW, Allen WR. 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) 42:636–42.
    doi: 10.1111/j.2042-3306.2010.00112.xpubmed: 20840579google scholar: lookup
  63. Stewart MC, Stewart AA. Mesenchymal stem cells: characteristics, sources, and mechanisms of action.. Vet Clin North Am Equine Pract (2011) 27:243–61.
    doi: 10.1016/j.cveq.2011.06.004pubmed: 21872757google scholar: lookup
  64. Meyerrose TE, De Ugarte DA, Hofling AA, Herrbrich PE, Cordonnier TD, Shultz LD. In vivo distribution of human adipose-derived mesenchymal stem cells in novel xenotransplantation models.. Stem Cells (2007) 25:220–7.
    doi: 10.1634/stemcells.2006-0243pmc: PMC4382309pubmed: 16960135google scholar: lookup
  65. Peterson JD. General and technical considerations for background subtraction in 2D fluorescence using IVIS imaging systems.. Revvity, Inc (2023).
  66. Billinton N, Knight AW. Seeing the wood through the trees: a review of techniques for distinguishing green fluorescent protein from endogenous autofluorescence.. Anal Biochem (2001) 291:175–97.
    doi: 10.1006/abio.2000.5006pubmed: 11401292google scholar: lookup
  67. Troy T, Jekic-McMullen D, Sambucetti L, Rice B. Quantitative comparison of the sensitivity of detection of fluorescent and bioluminescent reporters in animal models.. Mol Imaging (2004) 3:9–23.
    doi: 10.1162/15353500200403196pubmed: 15142408google scholar: lookup
  68. Mcmullen RJ, Passler T. Diseases of the eye.. In: Sheep, Goat, and Cervid Medicine. 3rd edn. (2020). p. 349–84.

Citations

This article has been cited 4 times.
  1. Young KAS, Schnabel LV, Gilger BC. Cell and Gene Therapy in Equine Ocular Disease. Vet Ophthalmol 2026 Mar;29(2):e70151.
    doi: 10.1111/vop.70151pubmed: 41623202google scholar: lookup
  2. Shi L, Khan MZ, Ullah A, Liang H, Geng M, Akhtar MF, Na J, Han Y, Wang C. Advancements in Stem Cell Applications for Livestock Research: A Review. Vet Sci 2025 Apr 23;12(5).
    doi: 10.3390/vetsci12050397pubmed: 40431490google scholar: lookup
  3. Fleischer AB, Amann B, von Toerne C, Degroote RL, Schmalen A, Weißer T, Hauck SM, Deeg CA. Differential Expression of ARG1 and MRC2 in Retinal Müller Glial Cells During Autoimmune Uveitis. Biomolecules 2025 Feb 14;15(2).
    doi: 10.3390/biom15020288pubmed: 40001591google scholar: lookup
  4. An W, Zhang W, Qi J, Xu W, Long Y, Qin H, Yao K. Mesenchymal stem cells and mesenchymal stem cell-derived exosomes: a promising strategy for treating retinal degenerative diseases. Mol Med 2025 Feb 21;31(1):75.
    doi: 10.1186/s10020-025-01120-wpubmed: 39984849google scholar: lookup
Subscribe to our newsletter
Join 99,658 horse owners like you who receive our email updates on horse health and nutrition.