Skip to main content
SpringerLink
Log in

Mesenchymal Stem Cells Therapeutic Applications in Cardiovascular Disorders

  • Chapter
  • First Online:
Therapeutic Applications of Mesenchymal Stem Cells in Veterinary Medicine

  • 203 Accesses

Abstract

Diseases of the heart are often serious considering the physiological role played by it. There are many heart diseases (HDs) that lack effective treatment and most of the diseases need lifelong palliative treatment. To ensure actual cardiac tissue regeneration and/or prevent any underlying ailment, regenerative medicine employing stem cells especially mesenchymal stem cells (MSCs) is being evaluated. Under in vitro environments, MSCs potentially differentiate into cardiomyocyte-like cells and secrete various paracrine pro-healing factors. In numerous in vivo experimental studies, MSCs therapeutic benefits too are reported. In veterinary cardiology, a limited literature on therapeutic efficacy of MSCs is available. Small animals like sheep and dog are utilized as translational model animals for humans especially for the ischaemic cardiomyopathies (myocardial infarction), valvular affections and biological pacemaker. However, clinical therapeutics based on MSCs remain to be standardized. Clinically, MSCs are studied for dog cardiomyopathy or myxomatous mitral valve disease (MMVD) without any significant improvement. In cat chronic degenerative valvular heart disease, an improved outcome is reported. The current chapter discusses the literature on MSCs potential therapeutic role for various cardiovascular ailments.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ahmad T, Mukherjee S, Pattnaik B, Kumar M, Singh S, Kumar M, Rehman R, Tiwari BK, Jha KA, Barhanpurkar AP et al (2014) Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy. EMBO J 33:994–1010

    CAS  PubMed  PubMed Central  Google Scholar 

  • Airey JA, Almeida-Porada G, Colletti EJ, Porada CD, Chamberlain J, Movsesian M, Sutko JL, Zanjani ED (2004) Human mesenchymal stem cells form Purkinje fibers in fetal sheep heart. Circulation 109:1401–1407

    Article  PubMed  Google Scholar 

  • Aktas MS, Ozkanlar Y, Oruc E, Sozdutmaz I, Kirbas A (2015) Myocarditis associated with foot-and-mouth disease in suckling calves. Vet Arhiv 85(3):273–282

    Google Scholar 

  • Alexakis C, Partridge T, Bou-Gharios G (2007) Implication of the satellite cell in dystrophic muscle fibrosis: a self-perpetuating mechanism of collagen overproduction. Am J Physiol Cell Physiol 293:C661–C669

    Article  CAS  PubMed  Google Scholar 

  • Alexandre N, Ribeiro J, Gärtner A, Pereira T, Amorim I, Fragoso J, Lopes A, Fernandes J, Costa E, Santos-Silva A, Rodrigues M, Santos JD, Maurício AC, Luís AL (2014) Biocompatibility and hemocompatibility of polyvinyl alcohol hydrogel used for vascular grafting—in vitro and in vivo studies. Biomed Mater Res 102(12):4262–4275

    Google Scholar 

  • Amable PR, Teixeira MV, Carias RB, Granjeiro JM, Borojevic R (2014) Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton’s jelly. Stem Cell Res Ther 5:53

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Angert D, Berretta RM, Kubo H, Zhang H, Chen X, Wang W, Ogorek B, Barbe M, Houser SR (2011) Repair of the injured adult heart involves new myocytes potentially derived from resident cardiac stem cells. Circ Res 108:1226–1237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baisan RA, Condurachi E, Turcu CA, Vu V (2021) Prevalence of cardiac diseases in small animals: a five-year single-centre retrospective study. Rev Rom Med Vet 31(2):35–40

    Google Scholar 

  • Bartunek J, Croissant JD, Wijns W, Gofflot S, de Lavareille A, Vanderheyden M, Kaluzhny Y, Mazouz N, Willemsen P, Penicka M, Mathieu M, Homsy C, De Bruyne B, McEntee K, Lee IW, Heyndrickx GR (2007) Pretreatment of adult bone marrow mesenchymal stem cells with cardiomyogenic growth factors and repair of the chronically infarcted myocardium. Am J Physiol Heart Circ Physiol 292:H1095–H1104

    Article  CAS  PubMed  Google Scholar 

  • Beigi F, Schmeckpeper J, Pow-Anpongkul P, Payne JA, Zhang L, Zhang Z, Huang J, Mirotsou M, Dzau VJ (2013) C3orf58, a novel paracrine protein, stimulates cardiomyocyte cell-cycle progression through the PI3K-AKT-CDK7 pathway. Circ Res 113:372–380

    Article  CAS  PubMed  Google Scholar 

  • Bian S, Zhang L, Duan L, Wang X, Min Y, Yu H (2014) Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model. J Mol Med (Berl) 92:387–397

    Article  CAS  Google Scholar 

  • Boemo CM, Tucker JC, Huntington PJ et al (1991) Monensin toxicity in horses: an outbreak resulting in the deaths of ten horses. Aust Vet J 9:103

    Google Scholar 

  • Bonagura JD (2019) Overview of equine cardiac disease. Vet Clin North Am Equine Pract 35(1):1–22. https://doi.org/10.1016/j.cveq.2019.01.001

    Article  PubMed  Google Scholar 

  • Borgarelli M, Buchanan JW (2012) Historical review, epidemiology and natural history of degenerative mitral valve disease. J Vet Cardiol 14:93–101

    Article  PubMed  Google Scholar 

  • Bortolotti F, Ruozi G, Falcione A, Doimo S, Dal Ferro M, Lesizza P, Zentilin L, Banks L, Zacchigna S, Giacca M (2017) In vivo functional selection identifies Cardiotrophin-1 as a cardiac engraftment factor for mesenchymal stromal cells. Circulation 136:1509–1524

    Article  CAS  PubMed  Google Scholar 

  • Boswood A, Haggstrom J, Gordon SG et al (2016) Effect of pimobendan in dogs with preclinical myxomatous mitral valve disease and cardiomegaly: the EPIC study—a randomized clinical trial. J Vet Intern Med 30:1765–1779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buczinski S, Fecteau G, Francoz D et al (2005) Les affections cardiaques congénitales du veau : une approche clinique diagnostique simple. Med Vet Québec 35:79–85

    Google Scholar 

  • Buczinski S, Fecteau G, DiFruscia R (2006) Ventricular septal defects in cattle: 25 cases. Can Vet J 47:246–252

    PubMed  PubMed Central  Google Scholar 

  • Carrade DD, Lame MW, Kent MS, Clark KC, Walker NJ, Borjesson DL (2012) Comparative analysis of the immunomodulatory properties of equine adult-derived mesenchymal stem cells. Cell Med 4(1):1–11

    Article  PubMed  PubMed Central  Google Scholar 

  • Cassano JM, Fortier LA, Hicks RB, Harman RM, Van de Walle GR (2018) Equine mesenchymal stromal cells from different tissue sources display comparable immune-related gene expression profiles in response to interferon gamma (IFN)-γ. Vet Immunol Immunopathol 202:25–30

    Article  CAS  PubMed  Google Scholar 

  • Cerrada I, Ruiz-Saurí A, Carrero R, Trigueros C, Dorronsoro A, Sanchez-Puelles JM, Diez-Juan A, Montero JA, Sepúlveda P (2013) Hypoxia-inducible factor 1 alpha contributes to cardiac healing in mesenchymal stem cells-mediated cardiac repair. Stem Cells Dev 22:501–511

    Article  CAS  PubMed  Google Scholar 

  • Cervio E, Barile L, Moccetti T, Vassalli G (2015) Exosomes for intramyocardial intercellular communication. Stem Cells Int 2015:482171

    Article  PubMed  PubMed Central  Google Scholar 

  • Chang X, Liu J, Liao X, Liu G (2015) Ultrasound-mediated microbubble destruction enhances the therapeutic effect of intracoronary transplantation of bone marrow stem cells on myocardial infarction. Int J Clin Exp Pathol 8(2):2221–2234

    PubMed  PubMed Central  Google Scholar 

  • Cheng Y, Yi G, Conditt GB, Sheehy A, Kolodgie FD, Tellez A, Polyakov I, Gu A, Aboodi MS, Wallace-Bradley D, Schuster M, Martens T, Itescu S, Kaluza GL, Basu S, Virmani R, Granada JF, Sherman W (2013) Catheter-based endomyocardial delivery of mesenchymal precursor cells using 3D echo guidance improves cardiac function in a chronic myocardial injury sheep model. Cell Transplant 22(12):2299–2309

    Article  PubMed  Google Scholar 

  • Chiu CP, Blau HM (1985) 5-Azacytidine permits gene activation in a previously noninducible cell type. Cell 40:417–424

    Article  CAS  PubMed  Google Scholar 

  • Chung ES, Miller L, Patel AN, Anderson RD, Mendelsohn FO, Traverse J, Silver KH, Shin J, Ewald G, Farr MJ et al (2015) Changes in ventricular remodelling and clinical status during the year following a single administration of stromal cell-derived factor-1 non-viral gene therapy in chronic ischaemic heart failure patients: the STOP-HF randomized phase II trial. Eur Heart J 36:2228–2238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cunningham M, Rush JE (2007) Transvenous pacemaker placement in a dog with atrioventricular block and persistent left cranial vena cava Suzanne. J Vet Cardiol 9:129–134

    Article  PubMed  Google Scholar 

  • Darke PGG (1985) Myocardial disease in small animals. Br Vet J 141:342

    Article  CAS  PubMed  Google Scholar 

  • Darke PGG (1986) Congenital heart defects in small animals. Br Vet J 142:203

    Article  CAS  PubMed  Google Scholar 

  • Davis JL, Gardner SY, Schwabenton B, Breuhaus BA (2002) Congestive heart failure in horses: 14 cases (1984–2001). JAVMA 220(10):1512–1515

    Article  PubMed  Google Scholar 

  • Dayan V, Sotelo V, Delfina V, Delgado N, Rodriguez C, Suanes C, Langhain M, Ferrando R, Armand K, Benech A, Touriño C (2016) Human mesenchymal stromal cells improve cardiac perfusion in an sheep immunocompetent animal model. J Invest Surg 29(4):1–8

    Article  Google Scholar 

  • De Lisio M, Jensen T, Sukiennik RA, Huntsman HD, Boppart MD (2014) Substrate and strain alter the muscle-derived mesenchymal stem cell secretome to promote myogenesis. Stem Cell Res Ther 5:74

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Di Francesco D (2010) The role of the funny current in pacemaker activity. Circ Res 106:434–446

    Article  CAS  Google Scholar 

  • Dill SG, Moise NS, Meschter CL (1986) Cardiac failure in a stallion secondary to metastasis of an anaplastic pulmonary carcinoma. Equine Vet J 18:414–417

    Article  CAS  PubMed  Google Scholar 

  • Dillon AR, Dell’Italia LJ, Tillson M et al (2012) Left ventricular remodeling in preclinical experimental mitral regurgitation of dogs. J Vet Cardiol 14:73–92

    Article  PubMed  Google Scholar 

  • DiVincenti LJ, Westcott R, Lee C (2014) Sheep (Ovis aries) as a model for cardiovascular surgery and management before, during, and after cardiopulmonary bypass. J Am Assoc Lab Anim Sci 53(5):439–448

    PubMed  PubMed Central  Google Scholar 

  • Dixon JA, Gorman RC, Stroud RE, Bouges S, Hirotsugu H, Gorman JH, Martens TP, Itescu S, Schuster MD, Plappert T, St John-Sutton MG, Spinale FG (2009) Mesenchymal cell transplantation and myocardial remodeling after myocardial infarction. Circulation 120(11):S220–S229

    CAS  PubMed  PubMed Central  Google Scholar 

  • Donders R, Bogie JFJ, Ravanidis S, Gervois P, Vanheusden M, Marée R, Schrynemackers M, Smeets HJM, Pinxteren J, Gijbels K et al (2018) Human Wharton’s jelly-derived stem cells display a distinct immunomodulatory and proregenerative transcriptional signature compared to bone marrow-derived stem cells. Stem Cells Dev 27:65–84

    Article  CAS  PubMed  Google Scholar 

  • Driehuys S, Van Winkle TJ, Sammarco CD, Drobatz KJ (1998) Myocardial infarction in dogs and cats: 37 cases (1985–1994). J Am Vet Med Assoc 213(10):1444–1448

    CAS  PubMed  Google Scholar 

  • Emmert MY, Weber B, Wolint P, Frauenfelder T, Zeisberger SM, Behr L, Sammut S, Scherman J, Brokopp CE, Schwartländer R, Vogel V, Vogt P, Grünenfelder J, Alkadhi H, Falk V, Boss A, Hoerstrup SP (2013) Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model: a proof of concept study. PLoS One 8(3):e57759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Engelmayr GC, Sacks MS (2006) A structural model for the flexural mechanics of nonwoven tissue engineering scaffolds. J Biomech Eng 128:610–622

    Article  PubMed  Google Scholar 

  • Ford J, McEndaffer L, Renshaw R, Molesan A, Kelly K (2017) Parvovirus infection is associated with myocarditis and myocardial fibrosis in young dogs. Vet Pathol 54(6):964–971

    Article  PubMed  Google Scholar 

  • Fu H, Chen Q (2020) Mesenchymal stem cell therapy for heart failure: a meta-analysis. Herz 45(6):557–563

    Article  CAS  PubMed  Google Scholar 

  • Fukushima S, Varela-Carver A, Coppen SR et al (2007) Direct intramyocardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model. Circulation 115:2254–2261

    Article  PubMed  Google Scholar 

  • Golpanian S, Wolf A, Hatzistergos KE, Hare JM (2016) Rebuilding the damaged heart: mesenchymal stem cells, cell-based therapy, and engineered heart tissue. Physiol Rev 96:1127–1168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grieve SM, Bhindi R, Seow J, Doyle A, Turner AJ, Tomka J, Lay W, Gill A, Hunyor SN, Figtree GA (2010) Microvascular obstruction by intracoronary delivery of mesenchymal stem cells and quantification of resulting myocardial infarction by cardiac magnetic resonance. Circ Heart Fail 3:e5–e6

    Article  PubMed  Google Scholar 

  • Gugjoo MB, Hoque M, Saxena AC, Zama MMS (2013) Radiographic, electrocardiographic and echocardiographic features of dilatation cardiomyopathy. Indian Vet J 90:19–22

    Google Scholar 

  • Gugjoo MB, Saxena AC, Hoque M, Zama MMS (2014) M–mode echocardiographic study in dogs. Afr J Agr Res 9(3):387–396

    Article  Google Scholar 

  • Gugjoo MB, Amarpal CV, Wani MY, Dhama K, Sharma GT (2018) Mesenchymal stem cell research in veterinary medicine. Curr Stem Cell Res Ther 13(8):645–657

    Article  CAS  PubMed  Google Scholar 

  • Gugjoo MB, Amarpal I, Makhdoomi DM, Sharma GT (2019) Equine mesenchymal stem cells: properties, sources, characterization and potential therapeutic applications. J Equine Vet Sci 72:16–27

    Article  PubMed  Google Scholar 

  • Gugjoo MB, Hussain S, Amarpal SRA, Dhama K (2020) Mesenchymal stem cell-mediated immuno-modulatory and anti-inflammatory mechanisms in immune and allergic disorders. Recent Pat Inflamm Allergy Drug Discov 14:000–000

    Article  CAS  Google Scholar 

  • Gugjoo MB, Dar SH, Ahamd RA, Hussain HA, Dar MD, Parrah JD, Dhama K (2021) Traumatic reticuloperitonitis in cattle and buffalo: recent advances in understanding of etiopathogenesis, diagnosis and treatment. Indian J Anim Sci 91(11):895–905

    Google Scholar 

  • Hamamoto H, Gorman JH, Ryan LP, Hinmon R, Martens TP, Schuster MD, Plappert T, Kiupel M, St John-Sutton MG, Itescu S, Gorman RC (2009) Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial infarction: the effect of cell dosage. Ann Thorac Surg 87(3):794–801

    Article  PubMed  PubMed Central  Google Scholar 

  • Hao LJ, Hao J, Fang W, Han C, Zhang K, Wang X (2015) Dual isotope simultaneous imaging to evaluate the effects of intracoronary bone marrow-derived mesenchymal stem cells on perfusion and metabolism in canines with acute myocardial infarction. Biomed Rep 3:447–452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hatzistergos KE, Quevedo H, Oskouei BN, Hu Q, Feigenbaum GS, Margitich IS, Mazhari R, Boyle AJ, Zambrano JP, Rodriguez JE et al (2010) Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circ Res 107:913–922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hatzistergos KE, Saur D, Seidler B, Balkan W, Breton M, Valasaki K, Takeuchi LM, Landin AM, Khan A, Hare JM (2016) Stimulatory effects of mesenchymal stem cells on cKit+ cardiac stem cells are mediated by SDF1/CXCR4 and SCF/cKit signaling pathways. Circ Res 119:921–930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Healy AM (1996) Endocarditis in cattle: a review of 22 cases. Ir Vet J 49:43–48

    Google Scholar 

  • Hnatiuk AP, Ong S-G, Olea FD, Locatelli P, Riegler J, Lee WH, Jen CH, De Lorenzi A, Gimenez CS, Laguens R, Wu JC, Crottogini A (2016) Allogeneic mesenchymal stromal cells overexpressing mutant human hypoxia-inducible factor 1-a (HIF1-a) in an sheep model of acute myocardial infarction. J Am Heart Assoc 5:e003714

    Article  PubMed  PubMed Central  Google Scholar 

  • Hou Y-B, Zou C-W, Wang Y, Li D-C, Li Q-B, Li H-X, Zhang H-Z, Zhang Q, Fan Q-X (2011) Establishing a new electrical conduction pathway by anastomosis of the right auricle and right ventricle assisted by mesenchymal stem cells in a canine model. Transplant Proc 43:3980–3986

    Article  PubMed  Google Scholar 

  • Houtgraaf JH, de Jong R, Kazemi K, de Groot D, van der Spoel TI, Arslan F, Hoefer I, Pasterkamp G, Itescu S, Zijlstra F, Geleijnse ML, Serruys PW, Duckers HJ (2013) Intracoronary infusion of allogeneic mesenchymal precursor cells directly after experimental acute myocardial infarction reduces infarct size, abrogates adverse remodeling, and improves cardiac function. Circ Res 113(2):153–166

    Article  CAS  PubMed  Google Scholar 

  • Jain AK, Smith EJ, Rothman MT (2006) The coronary venous system: an alternative route of access to the myocardium. J Invasive Cardiol 18(11):563–568

    PubMed  Google Scholar 

  • Jin Y, Kong H, Stodilka RZ, Wells RG, Zabel P, Merrifield PA, Sykes J, Prato FS (2005) Determining the minimum number of detectable cardiac-transplanted 111In-tropolone-labelled bone-marrow-derived mesenchymal stem cells by SPECT. Phys Med Biol 50:4445–4455

    Article  PubMed  Google Scholar 

  • Johnson MS, Martin MWS, Henley W (2007) Results of pacemaker implantation in 104 dogs. J Small Anim Pract 48:4–11

    Article  CAS  PubMed  Google Scholar 

  • Jun C, Zhihui Z, Lu W, Yaoming N, Lei W, Yao Q, Zhiyuan S (2012) Canine bone marrow mesenchymal stromal cells with lentiviral mHCN4 gene transfer creates cardiac pacemakers. Cytotherapy 14:529–539

    Article  PubMed  CAS  Google Scholar 

  • Kalfa D, Bel A, Chen-Tournoux A, Martina AD, Rochereau P, Coz C, Bellamy V, Bensalah M, Vanneaux V, Lecourt S, Mousseaux E, Bruneval P, Larghero J, Menasche P (2010) A polydioxanone electrospun valved patch to replace the right ventricular outflow tract in a growing lamb model. Biomaterials 31:4056–4063

    Article  CAS  PubMed  Google Scholar 

  • Kim SK, Pak H-N, Park JH, Fang YF, Kim GI, Park YD, Hwang C, Kim Y-H, Kim BS (2010) Cardiac cell therapy with mesenchymal stem cell induces cardiac nerve sprouting, angiogenesis, and reduced connexin43-positive gap junctions, but concomitant electrical pacing increases connexin43-positive gap junctions in canine heart. Cardiol Young 20(3):308–317

    Article  PubMed  Google Scholar 

  • Kim U, Shin D-G, Park J-S, Kim Y-J, Park S-I, Moon Y-M, Jeong K-S (2011) Homing of adipose-derived stem cells to radiofrequency catheter ablated canine atrium and differentiation into cardiomyocyte-like cells. Int J Cardiol 146:371–378

    Article  PubMed  Google Scholar 

  • Lee WS, Suzuki Y, Graves SS, Iwata M, Venkataraman GM, Mielcarek M et al (2011) Canine bone marrow-derived mesenchymal stromal cells suppress alloreactive lymphocyte proliferation in vitro but fail to enhance engraftment in canine bone marrow transplantation. Biol Blood Marrow Transplant 17(4):465–475

    Article  PubMed  Google Scholar 

  • Liao B, Deng L, Wang F (2006) Effects of bone marrow mesenchymal stem cells enriched by small intestinal submucosal films on cardiac function and compensatory circulation after myocardial infarction in goats. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 20(12):1248–1252

    PubMed  Google Scholar 

  • Ling Z-Y, Shu S-Y, Zhong S-G, Luo J, Su L, Liu Z-Z, Lan X-B, Yuan GB, Zheng Y-Y, Ran H-T, Wang Z-G, Y-H YIN (2013) Ultrasound targeted microbubble destruction promotes angiogenesis and heart function by inducing myocardial microenvironment change. Ultrasound Med Biol 39(11):2001–2010

    Article  PubMed  Google Scholar 

  • Liu Y, Song J, Liu W et al (2003) Growth and differentiation of rat bone marrow stromal cells: does 5-azacytidine trigger their cardiomyogenic differentiation? Cardiovasc Res 58:460–468

    Article  CAS  PubMed  Google Scholar 

  • Locatelli P, Olea FD, Hnatiuk A, De Lorenzi A, Cerdá M, Giménez CS, Sepúlveda D, Laguens R, Crottogini A (2015) Mesenchymal stromal cells overexpressing vascular endothelial growth factor in sheep myocardial infarction. Gene Ther 22(6):449–457

    Article  CAS  PubMed  Google Scholar 

  • Loffredo FS, Steinhauser ML, Gannon J, Lee RT (2011) Bone marrow derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell 8:389–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu W, Yaoming N, Boli R, Jun C, Changhai Z, Yang Z, Zhiyuan S (2013) mHCN4 genetically modified canine mesenchymal stem cells provide biological Pacemaking function in complete dogs with atrioventricular block. PACE 36:1138–1149

    Article  PubMed  Google Scholar 

  • Ma N, Ding F, Zhang J, Bao C, Zhong H, Mei J (2013) Myocardial structural protein expression in umbilical cord blood mesenchymal stem cells after myogenic induction. Cell Biol Int 37:899–904

    Article  CAS  PubMed  Google Scholar 

  • Margaryan R, Assanta N, Menciassi A, Burchielli S, Matteucci M, Agostini S, Lionetti V, Luchi C, Cariati E, Pucci A, Coceani F, Murzi B (2020) Selective perfusion of coronary vasculature in preterm sheep: a methodological innovation undermined by unfavourable operation of the foramen ovale. Can J Physiol Pharmacol 98:211–218

    Article  CAS  PubMed  Google Scholar 

  • Marr CM, Reef VB, Brazil TJ et al (1998) Aorto-cardiac fistulas in seven horses. Vet Radiol Ultrasound 39:22–31

    Article  CAS  PubMed  Google Scholar 

  • Mathieu M, Bartunek J, El Oumeiri B, Touihri K, Hadad I, Thoma P, Metens T, da Costa AM, Mahmoudabady M, Egrise D, Blocklet D, Mazouz N, Naeije R, Heyndrickx G, McEntee K (2009) Cell therapy with autologous bone marrow mononuclear stem cells is associated with superior cardiac recovery compared with use of nonmodified mesenchymal stem cells in a canine model of chronic myocardial infarction. J Thorac Cardiovasc Surg 138(3):646–653

    Article  PubMed  Google Scholar 

  • Menasché P (2009) Stem cell therapy for heart failure: are arrhythmias a real safety concern? Circulation 119(20):2735–2740

    Article  PubMed  Google Scholar 

  • Mendelson K, Aikawa E, Mettler BA, Sales V, Martin D, Mayer JE, Schoen FJ (2007) Healing and remodeling of bioengineered pulmonary artery patches implanted in sheep. Cardiovasc Pathol 16:277–282

    Article  CAS  PubMed  Google Scholar 

  • Mettler BA, Sales VL, Stucken CL, Anttila V, Mendelson K, Bischoff J, Mayer JE (2008) Stem cell–derived, tissue-engineered pulmonary artery augmentation patches in vivo. Ann Thorac Surg 86:132

    Article  PubMed  Google Scholar 

  • Mias C, Lairez O, Trouche E, Roncalli J, Calise D, Seguelas MH, Ordener C, Piercecchi-Marti MD, Auge N, Salvayre AN et al (2009) Mesenchymal stem cells promote matrix metalloproteinase secretion by cardiac fibroblasts and reduce cardiac ventricular fibrosis after myocardial infarction. Stem Cells 27:2734–2743

    Article  CAS  PubMed  Google Scholar 

  • Miller PJ, Holmes JR (1985) Observations on seven cases of mitral insufficiency in the horse. Equine Vet J 17:181–190

    Article  CAS  PubMed  Google Scholar 

  • Minguell JJ, Florenzano FM, Ramírez MR, Martínez RF, Lasala GP (2010) Intracoronary infusion of a combination of bone marrow-derived stem cells in dogs. Exp Clin Cardiol 15(2):17–20

    PubMed  PubMed Central  Google Scholar 

  • Mirotsou M, Zhang Z, Deb A, Zhang L, Gnecchi M, Noiseux N, Mu H, Pachori A, Dzau V (2007) Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci U S A 104:1643–1648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakanishi C, Nagaya N, Ohnishi S, Yamahara K, Takabatake S, Konno T, Hayashi K, Kawashiri MA, Tsubokawa T, Yamagishi M (2011) Gene and protein expression analysis of mesenchymal stem cells derived from rat adipose tissue and bone marrow. Circ J 75:2260–2268

    Article  CAS  PubMed  Google Scholar 

  • Nart P, Thompson H, Barrett DC et al (2004) Clinical and pathological features of dilated cardiomyopathy in Holstein-Friesian cattle. Vet Rec 155:355–361

    Article  CAS  PubMed  Google Scholar 

  • Nout YS, Hinchcliff KW, Bonagura JD, Meurs KM, Papenfuss TL (2003) Cardiac amyloidosis in a horse. J Vet Intern Med 17:588–592

    Article  PubMed  Google Scholar 

  • Ouyang H, Zhang JB, Liu Y, Li Q, Peng YH, Kang XJ, Wang YM, Wei XF, Yi DH, Liu WY (2008) Research on application of modified polyethylene glycol hydrogels in the construction of tissue engineered heart valve. Zhonghua Wai KeZaZhi 46(22):1723–1726

    Google Scholar 

  • Parker HG, Kilroy-Glynn P (2012) Myxomatous mitral valve disease in dogs: does size matter? J Vet Cardiol 14(1):19–29

    Article  PubMed  PubMed Central  Google Scholar 

  • Perin EC, Silva GV, Assad JA, Vela D, Buja LM, Sousa AL et al (2008) Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. J Mol Cell Cardiol 44(3):486–495

    Article  CAS  PubMed  Google Scholar 

  • Petchdee S, Sompeewong S (2016) Intravenous administration of puppy deciduous teeth stem cells in degenerative valve disease. Vet World 9(12):1429–1434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petchdee S, Chanda M, Cherdchutham W (2018) Pacemaker implantation in horse with bradycardia-tachycardia syndrome. Asian J Anim Vet Adv 13:35–42

    Article  Google Scholar 

  • Plotnikov AN, Shlapakova I, Szabolcs MJ, Danilo P, Lorell BH, Potapova IA, Lu Z, Rosen AB, Mathias RT, Brink PR, Robinson RB, Cohen IS, Rosen MR (2007) Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart. Circulation 116:706–713

    Article  PubMed  Google Scholar 

  • Pogue B, Estrada AH, Sosa-Samper I, Maisenbacher HW, Lamb KE, Mincey BD, Erger KE, Conlon TJ (2013) Stem-cell therapy for dilated cardiomyopathy: a pilot study evaluating retrograde coronary venous delivery. J Small Anim Pract 54(7):361–366

    Article  CAS  PubMed  Google Scholar 

  • Potapova IA, Doronin SV, Kelly DJ, Rosen AB, Schuldt AJT, Lu Z, Kochupura PV, Robinson RB, Rosen MR, Brink PR, Gaudette GR, Cohen IS (2008) Enhanced recovery of mechanical function in the canine heart by seeding an extracellular matrix patch with mesenchymal stem cells committed to a cardiac lineage. Am J Physiol Heart Circ Physiol 295:H2257–H2263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Psaltis PJ, Carbone A, Nelson A et al (2008) An ovine model of toxic, nonischemic cardiomyopathy—assessment by cardiac magnetic resonance imaging. J Card Fail 14:785–795

    Article  PubMed  Google Scholar 

  • Psaltis PJ, Carbone A, Nelson AJ, Lau DH, Jantzen T, Manavis J, Williams K, Itescu S, Sanders P, Gronthos S, Zannettino ACW, Worthley SG (2010) Reparative effects of allogeneic mesenchymal precursor cells delivered transendocardially in experimental nonischemic cardiomyopathy. J Am Coll Cardiol Intv 3(9):974–983

    Article  Google Scholar 

  • Qian Q, Qian H, Zhang X et al (2012) 5-Azacytidine induces cardiac differentiation of human umbilical cord-derived mesenchymal stem cells by activating extracellular regulated kinase. Stem Cells Dev 21:67–75

    Article  CAS  PubMed  Google Scholar 

  • Rabbani S, Soleimani M, Sahebjam M et al (2017) Effects of endothelial and mesenchymal stem cells on improving myocardial function in a sheep animal model. J Tehran Heart Cent 12(2):65–71

    PubMed  PubMed Central  Google Scholar 

  • Ramaswamy S, Gottlieb D, Engelmayr GC Jr, Aikawa E, Schmidt DE, Gaitan-Leon DM, Sales VL, Mayer JE Jr, Sacks MS (2010) The role of organ level conditioning on the promotion of engineered heart valve tissue development in-vitro using mesenchymal stem cells. Biomaterials 31:1114–1125

    Article  CAS  PubMed  Google Scholar 

  • Ramaswamy S, Boronyak SM, Le T, Holmes A, Sotiropoulos F, Sacks MS (2014) A novel bioreactor for Mechanobiological studies of engineered heart valve tissue formation under pulmonary arterial physiological flow conditions. J Biomech Eng 136(12):121009

    Article  PubMed  Google Scholar 

  • Reef VB (1990) A monensin outbreak in horses in the eastern United States: pathogenesis, clinical signs, and epidemiology. In: Proceedings of the 8th Annual Vet Med Forum, May 11–13, Washington, DC, p 619

    Google Scholar 

  • Reef VB (1995) Evaluation of ventricular septal defects in horses using two-dimensional and Doppler echocardiography. Equine Vet J Suppl 19:86–96

    Google Scholar 

  • Reef VB (1999) Cardiomyopathy and myocarditis in horses. World Equine Vet Rev 4:18–22

    Google Scholar 

  • Reef VB, Mcguirk SM (2015) Disease of cardiovascular system. In: Smith BP (ed) Large internal medicine, 5th edn. Elsevier, Amsterdam, pp 427–260

    Google Scholar 

  • Reef VB, Bain FT, Spencer PA (1998) Severe mitral regurgitation in horses: clinical, echocardiographic and pathologic findings. Equine Vet J 30:18–27

    Article  CAS  PubMed  Google Scholar 

  • Rothuizen J, Van Den Inch TSGAM, VoorholI G, Van Der Leur RJT, Wouda W (1982) Congenital porto-systemic shunts in sixteen dogs and three cats. J Small Anim Pract 23:67

    Article  Google Scholar 

  • Row S, Swartz DD, Andreadis ST (2017) Animal models of cardiovascular disease as test beds of bioengineered vascular grafts. Drug Discov Today Dis Model 24:37

    Article  Google Scholar 

  • Scansen BA (2019) Equine congenital heart disease. Vet Clin North Am Equine Pract 35(1):103–117

    Article  PubMed  Google Scholar 

  • Scheinowitz M, Abramov D, Eldar M (1997) The role of insulin-like and basic fibroblast growth factors on ischemic and infarcted myocardium: a mini review. Int J Cardiol 59(1):1–5

    Article  CAS  PubMed  Google Scholar 

  • Schoen FJ, Hirsch D, Bianco RW, Levy RJ (1994) Onset and progression of calcification in porcine aortic bioprosthetic valves implanted as orthotopic mitral valve replacements in juvenile sheep. J Thorac Cardiovasc Surg 108(5):880–887

    Article  CAS  PubMed  Google Scholar 

  • Seppen J, Barry SC, Harder B, Osborne WR (2001) Lentivirus administration to rat muscle provides efficient sustained expression of erythropoietin. Blood 98:594–596

    Article  CAS  PubMed  Google Scholar 

  • Shabbir A, Zisa D, Lin H, Mastri M, Roloff G, Suzuki G, Lee T (2010) Activation of host tissue trophic factors through JAK-STAT3 signaling: a mechanism of mesenchymal stem cell-mediated cardiac repair. Am J Physiol Heart Circ Physiol 299:H1428–H1438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silva GV, Litovsky S, Assad JAR, Sousa ALS, Martin BJ, Vela D, Coulter SC, Lin J, Ober J, Vaughn WK, Branco RVC, Oliveira EM, He R, Geng Y-J, Willerson JT, Perin EC (2005) Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111:150–156

    Article  CAS  PubMed  Google Scholar 

  • Sinclair KA, Yerkovich ST, Hopkins PMA, Chambers DC (2016) Characterization of intercellular communication and mitochondrial donation by mesenchymal stromal cells derived from the human lung. Stem Cell Res Ther 7(1):91

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sinzobahamvya N, Boscheinen M, Blaschczok HC, Kallenberg R, Photiadis J, Haun C et al (2008) Survival and reintervention after neonatal repair of truncus arteriosus with valved conduit. Eur J Cardiothorac Surg 34:732–737

    Article  PubMed  Google Scholar 

  • Soltani L, Rahmani HR, Joupari MD, Ghaneialvar H, Mahdavi AH, Shamsara M (2016) Ovine fetal mesenchymal stem cell differentiation to cardiomyocytes, effects of co-culture, role of small molecules; reversine and 5-azacytidine. Cell Biochem Funct 34:250–261

    Article  CAS  PubMed  Google Scholar 

  • Sousa MG, Paulino-Junior D, Pascon JPE, Pereira-Neto GB, Carareto R, Champion T, Camacho AA (2011) Cardiac function in dogs with chronic Chagas cardiomyopathy undergoing autologous stem cell transplantation into the coronary arteries. Can Vet J 52(8):869–874

    PubMed  PubMed Central  Google Scholar 

  • Sun Q-W, Zhen L, Wang Q, Sun Y, Yang J, Li Y-J, Li R-J, Ma N, Li Z-A, Wang L-Y, Nie S-P, Yang Y (2016) Assessment of retrograde coronary venous infusion of mesenchymal stem cells combined with basic fibroblast growth factor in canine myocardial infarction using strain values derived from speckle-tracking echocardiography. Ultrasound Med Biol 42(1):272–281

    Article  PubMed  Google Scholar 

  • Suzuki G, Iyer V, Lee TC, Canty JM Jr (2011) Autologous mesenchymal stem cells mobilize cKit+ and CD133+ bone marrow progenitor cells and improve regional function in hibernating myocardium. Circ Res 109:1044–1054

    Article  CAS  PubMed  Google Scholar 

  • Taghavi S, Sharp TE, Duran JM, Makarewich CA, Berretta RM, Starosta T, Kubo H, Barbe M (2015) Autologous c-kit+ mesenchymal stem cell injections provide superior therapeutic benefit as compared to c-kit+ cardiac-derived stem cells in a feline model of isoproterenol-induced cardiomyopathy. Clin Transl Sci 8(5):425–431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uccelli A, Pistoia V, Moretta L (2007) Mesenchymal stem cells: a new strategy for immunosuppression? Trends Immunol 28:219–226

    Article  CAS  PubMed  Google Scholar 

  • Uechi M (2012) Mitral valve repair in dogs. J Vet Cardiol 14:185–192

    Article  PubMed  Google Scholar 

  • Urbich C, Dimmeler S (2004) Endothelial progenitor cells functional characterization. Trends Cardiovasc Med 14:318–322

    Article  CAS  PubMed  Google Scholar 

  • Vela DC, Silva GV, Assad JAR, Sousa ALS, Coulter S, Fernandes MR, Perin EC, Willerson JT, Buja LM (2009) Histopathological study of healing after allogenic mesenchymal stem cell delivery in myocardial infarction in dogs. J Histochem Cytochem 57:167–176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vollmar C, Vollmarb A, Keenec BW, Foxd PR, Reesee S, Kohn B (2019) Dilated cardiomyopathy in 151 Irish wolfhounds: characteristic clinical findings, life expectancy and causes of death. Vet J 245:15–21

    Article  CAS  PubMed  Google Scholar 

  • Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD (2004) Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 363:783–784

    Article  PubMed  Google Scholar 

  • Wang JS, Shum-Tim D, Galipeau J, Chedrawy E, Eliopoulos N, Chiu RC (2000) Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages. J Thorac Cardiovasc Surg 120:999–1005

    Article  CAS  PubMed  Google Scholar 

  • Wang G, Zhuo Z, Xia H, Zhang Y, He Y, Tan W, Gao Y (2013) Investigation into the impact of diagnostic ultrasound with microbubbles on the capillary permeability of rat hepatomas. Ultrasound Med Biol 39:628–637

    Article  PubMed  Google Scholar 

  • Wang X, Nie S-P, Zhen L, Miao H-T, Wu X-X, Ren H-M, Shi S-T (2014) Retrograde coronary venous infusion provides targeted cell engraftment into infarcted myocardium. Int J Cardiol 172:e279–e281

    Article  PubMed  Google Scholar 

  • Wang X, Zhen L, Miao H, Sun Q, Yang Y, Que B, Lopes Lao EP, Wu X, Ren H, Shi S, Lau WB, Ma X, Ma C, Nie S (2015) Concomitant retrograde coronary venous infusion of basic fibroblast growth factor enhances engraftment and differentiation of bone marrow mesenchymal stem cells for cardiac repair after myocardial infarction. Theranostics 5(9):995–1006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • West HJ (1988) Congenital anomalies of the bovine heart. Br Vet J 144:123–130

    Article  CAS  PubMed  Google Scholar 

  • Whitlock RH, White NA, Rowland GN et al (1978) Monensin toxicosis in horses: clinical manifestations. In: Proceedings. Annual Meetings of the American Association of Equine Practitioners, pp 473–486

    Google Scholar 

  • Worth LT, Reef VB (1998) Pericarditis in horses: 18 cases (1986–1995). J Am Vet Med Assoc 212:248–253

    CAS  PubMed  Google Scholar 

  • Xiao H, Yang Y-J, Lin Y-Z, Peng S, Lin S, Song Z-Y (2018) Transcription factor Tbx18 induces the differentiation of c-kit+ canine mesenchymal stem cells (cMSCs) into SAN-like pacemaker cells in a co-culture model in vitro. Am J Transl Res 10(8):2511–2528

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang VK, Meola DM, Davis A, Barton B, Hoffman AM (2021) Intravenous administration of allogeneic Wharton jelly–derived mesenchymal stem cells for treatment of dogs with congestive heart failure secondary to myxomatous mitral valve disease. Am J Vet Res 82(6):487–493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoon YS, Park JS, Tkebuchava T, Luedeman C, Losordo DW (2004) Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction. Circulation 109:3154–3157

    Article  PubMed  Google Scholar 

  • Yoshida J, Ohmori K, Takeuchi H, Shinomiya K, Namba T, Kondo I, Kiyomoto H, Kohno M (2005) Treatment of ischemic limbs based on local recruitment of vascular endothelial growth factor-producing inflammatory cells with ultrasonic microbubble destruction. J Am Coll Cardiol 46:899–905

    Article  PubMed  Google Scholar 

  • Zhang W, Huo Y, Wang X, Jia Y, Su L, Wang C, Li Y, Yang Y, Liu Y (2016a) Decellularized ovine arteries as biomatrix scaffold support endothelial of mesenchymal stem cells. Heart Vessels 31:1874–1881

    Article  PubMed  Google Scholar 

  • Zhang Z, Yang J, Yan W, Li Y, Shen Z, Asahara T (2016b) Pretreatment of cardiac stem cells with exosomes derived from mesenchymal stem cells enhances myocardial repair. J Am Heart Assoc 5:e002856

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao Y, Zhang S, Zhou J, Wang J, Zhen M, Liu Y, Chen J, Qi Z (2010) The development of a tissue-engineered artery using decellularized scaffold and autologous sheep mesenchymal stem cells. Biomaterials 31(2):296–307

    Article  PubMed  CAS  Google Scholar 

  • Zhao Y, Li T, Wei X, Bianchi G, Hu J, Sanchez PG, Xu K, Zhang P, Pittenger MF, WU J, Griffith BP. (2012) Mesenchymal stem cell transplantation improves regional cardiac remodeling following ovine infarction. Stem Cells Transl Med 1:685–695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng Y, Sampaio LC, Li K, Silva GV, Cabreira-Hansen M, Vela D, Segura AM, Bovè C, Perin EC (2013) Safety and feasibility of mapping and stem cell delivery in the presence of an implanted left ventricular assist device: a preclinical investigation in sheep. Tex Heart Inst J 40(3):229–234

    PubMed  PubMed Central  Google Scholar 

  • Zhou S, Chen LS, Miyauchi Y et al (2004) Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs. Circ Res 95:76–83

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Veterinary Clinical Complex, Faculty of Veterinary Sciences & Animal Husbandry, Sher-e-Kashmir University of Agricultural Sciences & Technology of Kashmir (SKUAST-K), Srinagar, Jammu and Kashmir, India

    Mudasir Bashir Gugjoo PhD

Authors
  1. Mudasir Bashir Gugjoo PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gugjoo, M.B. (2022). Mesenchymal Stem Cells Therapeutic Applications in Cardiovascular Disorders. In: Therapeutic Applications of Mesenchymal Stem Cells in Veterinary Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-19-3277-9_6

Download citation

Publish with us

Policies and ethics

Search

Navigation