Immune-mediated diseases affect millions of people worldwide with an economic impact measured in the billions of dollars. Mesenchymal stem cells (MSCs) are being investigated in the treatment of certain immune mediated diseases, but their application in the treatment of the majority of these disorders remains largely unexplored. Keratoconjunctivitis sicca can occur as a result of progressive immune-mediated destruction of lacrimal tissue in dogs and humans, and immune-mediated joint disease is common to both species. In dogs, allogeneic MSC engraftment and migration have yet to be investigated in vivo in the context of repeated injections.
Methods:
With these aims in mind, the engraftment of allogeneic canine MSCs after an injection into the periocular and intra-articular regions was followed in vivo using magnetic resonance and fluorescent imaging.
Results:
The cells were shown to be resident near the site of the injection for a minimum of 2 weeks. Analysis of 61 tissues demonstrated preferential migration and subsequent engraftment of MSCs in the thymus as well as the gastrointestinal tract. These results also detail a novel in vivo imaging technique and demonstrate the differential spatial distribution of MSCs after migration away from the sites of local delivery.
Conclusion:
The active engraftment of the MSCs in combination with their previously documented immunomodulatory capabilities suggests the potential for therapeutic benefit in using MSCs for the treatment of periocular and joint diseases with immune involvement.
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References
1.
AbderrahimH., Jaramillo-BabbV.L., ZhouZ., VollrathD.Characterization of the murine TIGR/myocilin gene. Mamm.Genome., 9:673–675. 1998.
2.
ReddyP., GradO., RajagopalanK.The economic burded on dry eye a conceptual framework and preliminary assessment. Cornea, 23:751–761. 2004.
3.
LinI.-C., GuptaP.K., BoehlkeC.S., LeeP.P.Documentation of conformance to preferred practice patterns in caring for patients with dry eye. Arch. Ophthalmol., 128:619–623. 2010.
4.
YuJ., AscheC.V., FairchildC.J.The economic burden of dry eye disease in the United States: a decision tree analysis. Cornea, 30:379–387. 2011.
5.
NguyenC.Q., SharmaA., SheJ.-X., McIndoeR.A., PeckA.B.Differential gene expressions in the lacrimal gland during development and onset of keratoconjunctivitis sicca in Sjögren's syndrome (SJS)-like disease of the C57BL/6.NOD-Aec1Aec2 mouse. Exp. Eye Res., 88:398–409. 2009.
6.
ZoukhriD.Effect of inflammation on lacrimal gland function. Exp. Eye Res., 82:885–898. 2006.
7.
MossS.E., KleinR., KleinB.E.K.Incidence of dry eye in an older population. Arch. Ophthalmol., 122:369–373. 2004.
8.
BoonenA., MauW.The economic burden of disease: comparison between rheumatoid arthiritis and ankylosing spndylitis. Clin. Exp. Rheumatol., 27:S112–S117. 2009.
9.
HelmickC.G., FelsonD.T., LawrenceR.C.et al.Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part I. Arthritis Rheum., 58:15–25. 2008.
10.
GabrielS., MichaudK.Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res. Ther., 11:229. 2009.
11.
NiebauerG.W., WolfB., BasheyR.I., NewtonC.D.Antibodies to canine collagen types I and II in dogs with spontaneous cruciate ligament rupture and osteoarthritis. Arthritis Rheum., 30:319–327. 1987.
CollettiE.J., AireyJ.A., LiuW.et al.Generation of tissue-specific cells from MSC does not require fusion or donor-to-host mitochondrial/membrane transfer. Stem Cell Res., 2:125–138. 2009.
14.
NeupaneM., ChangC.-C., KiupelM., Yuzbasiyan-GurkanV.Isolation and characterization of canine adipose–derived mesenchymal stem cells. Tiss. Eng. A., 14:1007–1015. 2008.
15.
VieiraN., BandaliseV., ZucconiE., SeccoM., StraussB., ZatzM.Isolation, characterization, and differentiation potential of canine adipose-derived stem cells. Cell Transplant., 19:279–289. 2010.
16.
KernS., EichlerH., StoeveJ., KlüterH., BiebackK.Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells., 24:1294–1301. 2006.
17.
ChungD.-J., HayashiK., ToupadakisC.A., WongA., YellowleyC.E.Osteogenic proliferation and differentiation of canine bone marrow and adipose tissue derived mesenchymal stromal cells and the influence of hypoxia. Res. Vet. Sci., 2010[Epub ahead of print]10.1016/j.rsvc.2010.10.012.
18.
MartinelloT., BronziniI., MaccatrozzoL.et al.Canine adipose-derived-mesenchymal stem cells do not lose stem features after a long-term cryopreservation. Res. Vet. Sci., 91:18–24. 2011.
LeeP.H., KimJ.W., BangO.Y., AhnY.H., JooI.S., HuhK.Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy. Clin. Pharmacol. Ther., 83:723–730. 2007.
26.
TyndallA., UccelliA.Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks. Bone Marrow Transpl., 43:821–828. 2009.
JungD.-I., HaJ., KangB.-T.et al.A comparison of autologous and allogenic bone marrow-derived mesenchymal stem cell transplantation in canine spinal cord injury. J. Neurol. Sci., 285:67–77. 2009.
29.
ChungD.-J., ChoiC.-B., LeeS.-H.et al.Intraarterially delivered human umbilical cord blood-derived mesenchymal stem cells in canine cerebral ischemia. J. Neurosci. Res., 87:3554–3567. 2009.
30.
VullietP.R., GreeleyM., HalloranS.M., MacDonaldK.A., KittlesonM.D.Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet, 363:783–784. 2004.
31.
BarbashI.M., ChouraquiP., BaronJ.et al.Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation, 108:863–868. 2003.
32.
LiechtyK.W., MacKenzieT.C., ShaabanA.F.et al.Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat. Med., 6:1282–1286. 2000.
33.
ToupadakisC.A., WongA., GenetosD.C.et al.Comparison of the osteogenic potential of equine mesenchymal stem cells from bone marrow, adipose tissue, umbilical cord blood, and umbilical cord tissue. Am. J. Vet. Res., 71:1237–1245. 2010.
34.
SosnovikD., NahrendorfM., WeisslederR.Magnetic nanoparticles for MR imaging: agents, techniques and cardiovascular applications. Basic Res. Cardiol., 103:122–130. 2008.
35.
FlexmanJ., CrossD., TranL., SasakiT., KimY., MinoshimaS.Quantitative analysis of neural stem cell migration and tracer clearance in the rat brain by MRI. Mol. Imaging Biol., 13:104–111. 2011.
36.
JendelováP., HerynekV., UrdzíkováL., GlogarováK., KroupováJ., AnderssonB., BryjaV., BurianM., HájekM., SykováE.Magnetic resonance tracking of transplanted bone marrow and embryonic stem cells labeled by iron oxide nanoparticles in rat brain and spinal cord. J. Neurosci. Res., 76:232–243. 2004.
37.
MelmanS.A.Skin Diseases of Dogs and Cats. Potomac, MD: DermaPet Inc., 1994.
38.
McKeeverP.J., NuttallT., HarveyR.G.A Color Handbook of Skin Diseases of the Dog and Cat. London: Manson Publishing, 2009.
39.
PattersonS.Skin Diseases of the Dog. Oxford: Blackwell Science Ltd, 1998.
40.
CampbellK.L.The Pet Lover's Guide to Cat & Dog Skin Diseases. St. Louis, MO: Elsevier Saunders, 2006.
41.
GrossT.L., IhrkeP.J., WalderE.J., AffolterV.K.Skin Diseases of the Dog and Cat: Clinical and Histopathological Diagnosis. Oxford: Blackwell Sciences, 2005.
42.
HongS.J., TraktuevD.O., MarchK.L.Therapeutic potential of adipose-derived stem cells in vascular growth and tissue repair. Curr. Opin. Organ Transplant., 15:86–91. 2010.
43.
MizunoH.Adipose-derived stem cells for tissue repair and regeneration: ten years of research and a literature review. J. Nippon Med. Sch., 76:56–66. 2009.
44.
NakaoN., NakayamaT., YahataT.Adipose tissue-derived mesenchymal stem cells facilitate hematopoiesis in vitro and in vivo: advantages over bone marrow-derived mesenchymal stem cells. Am. J. Pathol., 177:547–554. 2010.
45.
RamasamyR., TongC.K., SeowH.F., VidyadaranS., DazziF.The immunosuppressive effects of human bone marrow-derived mesenchymal stem cells target T cell proliferation but not its effector function. Cell. Immunol., 251:131–136. 2008.
46.
RiordanN.H., IchimT.E., MinW.-P.Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis. J. Transl. Med., 7:29. 2009, 10.1186/1979.5176.7.29.
SchäfflerA., BüchlerC.Concise review: adipose tissue-derived stromal cells—basic and clinical implications for novel cell-based therapies. Stem Cells, 25:818–827. 2007.
49.
SuniaraR.K., JenkinsonE.J., OwenJ.J.T.An essential role for thymic mesenchyme in early T cell development. J. Exp. Med., 191:1051–1056. 2000.
50.
JiangY., JahagirdarB.N., ReinhardtR.L.Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418:41–49. 2002.
51.
VodyanikM.A., YuJ., ZhangX.A mesoderm-derived precursor for mesenchymal stem and endothelial cells. Cell Stem Cell, 7:718–729. 2010.
52.
WoodJ.A.Human Endothelial Progenitor Cells: A Novel and Promising Cellular Therapy for Regenerative Medicine. Reno: School of Medicine, University of Nevada, 2009.
53.
HoriY., NakamuraT., KimuraD.Experimental study on tissue engineering of the small intestine by mesenchymal stem cell seeding. J. Surg. Res., 102:156–160. 2002.
54.
NakaseY., HagiwaraA., NakamuraT.Tissue engineering of small intestinal tissue using collagen sponge scaffolds seeded with smooth muscle cells. Tiss. Eng., 12:403–412. 2006.
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