期刊论文详细信息
Acta Veterinaria Scandinavica
Evaluation of adverse reactions in dogs following intravenous mesenchymal stem cell transplantation
Min Hee Kang1  Hee Myung Park1 
[1] Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea
关键词: Pulmonary hemorrhage;    MDCT;    Intravenous injection;    Mesenchymal stem cells;    Bone marrow;   
Others  :  789216
DOI  :  10.1186/1751-0147-56-16
 received in 2013-01-14, accepted in 2014-03-17,  发布年份 2014
PDF
【 摘 要 】

Background

Recent studies have assessed the therapeutic potential and drawbacks of mesenchymal stem cells (MSCs). The adverse reactions of intravenous transplantation of bone marrow (BM)-derived MSCs were examined at varying doses and frequencies of administration.

Nine healthy beagle dogs were purchased from a commercial laboratory. The dogs were distributed equally (n = 3 per group) and randomly into three groups. All dogs received allogeneic BM-derived MSCs: 2 × 106 once (group A), 2 × 107 once (group B), and 2 × 106 for three consecutive days (group C). Various laboratory examinations, multi-detector computed tomography features and histopathology were evaluated to clarify the clinical and diagnostic features of adverse reactions of MSCs administration, prior to receiving MSCs (pre procedure) and on days 1, 3, and 7 post transplantation.

Results

Only one dog had clinical signs during and after MSCs transplantation. Dogs receiving 2 × 106 MSCs showed increased numbers of lymphocytes but the total white blood cell counts were not elevated (P < 0.01). Multi-detector computed tomography (MDCT) revealed pulmonary parenchymal changes in one dog and histopathologic examination revealed pulmonary parenchymal edema and hemorrhage in four dogs. The presence of pulmonary thromboembolism was not detected in either examination.

Conclusions

We considered the presence of pulmonary edema and hemorrhage as possible adverse reactions after intravenous MSCs transplantation; however these results should be cautiously interpreted.

【 授权许可】

   
2014 Kang and Park; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140704170118741.pdf 828KB PDF download
Figure 3. 74KB Image download
Figure 2. 67KB Image download
Figure 1. 61KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】
  • [1]Bang OY, Lee JS, Lee PH, Lee G: Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005, 57:874-882.
  • [2]Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, Coulter SC, Lin J, Ober J, Vaughn WK, Branco RV, Oliveira EM, He R, Geng YJ, Willerson JT, Perin EC: Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 2005, 111:150-156.
  • [3]Strauer BE, Brehm M, Zeus T, Köstering M, Hernandez A, Sorg RV, Kögler G, Wernet P: Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002, 106:1913-1918.
  • [4]Kursova LV, Konoplyannikov AG, Pasov VV, Ivanova IN, Poluektova MV, Konoplyannikova OA: Possibilities for the use of autologous mesenchymal stem cells in the therapy of radiation-induced lung injuries. Bull Exp Biol Med 2009, 147:542-546.
  • [5]Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T, Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators: Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002, 360:427-435.
  • [6]Chen J, Li Y, Katakowski M, Chen X, Wang L, Lu D, Lu M, Gautam SC, Chopp M: Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. J Neurosci Res 2003, 73:778-786.
  • [7]Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Choop M: Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 2001, 32:1005-1011.
  • [8]Furlani D, Ugurlucan M, Ong L, Bieback K, Pittermann E, Westien I, Wang W, Yerebakan C, Li W, Gaebel R, Li RK, Vollmar B, Steinhoff G, Ma N: Is the intravascular administration of mesenchymal stem cells safe? Mesenchymal stem cells and intravital microscopy. Microvasc Res 2009, 77:370-376.
  • [9]Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD: Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 2004, 363:783-784.
  • [10]Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A, Miller L, Guetta E, Zipori D, Kedes LH, Kloner RA, Leor J: Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 2003, 108:863-868.
  • [11]Kang WJ, Kang HJ, Kim HS, Chung JK, Lee MC, Lee DS: Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction. J Nucl Med 2006, 47:1295-1301.
  • [12]Jung DI, Kim HJ, Kim JW, Kang BT, Yoo JH, Park C, Lee JH, Park HM: Canine mesenchymal stem cells derived from bone marrow: isolation, characterization, multidifferentiation, and neurotrophic factor expression in vitro. J Vet Clin 2008, 25:458-465.
  • [13]Goncalves AC, Orton EC, Boon JA, Salman MD: Linear, logarithmic, and polynomial models of m-mode echocardiographic measurements in dogs. Am J Vet Res 2002, 63:994-999.
  • [14]Boon JA: Manual of Veterinary Echocardiography. 2nd edition. Wiley-Blackwell: West Sussex, UK; 2011.
  • [15]Borqarelli M, Tarducci A, Zanatta R, Haggstrom J: Decreased systolic function and inadequate hypertrophy in large and small breed dogs with chronic mitral valve insufficiency. J Vet Intern Med 2007, 21:61-67.
  • [16]Maeda S, Fujiwara S, Omori K, Kawano K, Kurata K, Masuda K, Ohno K, Tsujimoto H: Lesional expression of thymus and activation-regulated chemokine in canine atopic dermatitis. Vet Immunol Immunopathol 2002, 88:79-87.
  • [17]Peters IR, Helps CR, Calvert EL, Hall EJ, Day MJ: Cytokine mRNA quantification in histologically normal canine duodenal mucosa by real-time RT-PCR. Vet Immunol Immunopathol 2005, 103:101-111.
  • [18]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001, 25:402-408.
  • [19]Fischer UM, Harting MT, Jimenez F, Monzon-Posadas WO, Xue H, Savitz SI, Laine GA, Cox CS Jr: Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells Dev 2009, 18:683-692.
  • [20]Aggarwal S, Pittenger MF: Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005, 105:1815-1822.
  • [21]Newman RE, Yoo D, LeRoux MA, Danilkovitch-Miagkova A: Treatment of inflammatory diseases with mesenchymal stem cells. Inflamm Allergy Drug Targets 2009, 8:110-123.
  • [22]Ponte AL, Marais E, Gallay N, Langonné A, Delorme B, Hérault O, Charbord P, Domenech J: The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells 2007, 25:1737-1745.
  • [23]Poncelet AJ, Vercruysse J, Saliez A, Gianello P: Although pig allogeneic mesenchymal stem cells are not immunogenic in vitro, intracardiac injection elicits an immune response in vivo. Transplantation 2007, 83:783-790.
  • [24]Sundin M, Ringden O, Sundberg B, Nava S, Götherström C, Le Blanc K: No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients. Haematologica 2007, 92:1208-1215.
  • [25]Yagihara H, Uematsu Y, Koike A, Tamura K, Isotani M, Yamaguchi T, Ono K, Washizu T, Bonkobara M: Immunophenotyping and gene rearrangement analysis in dogs with lymphoproliferative disorders characterized by small-cell lymphocytosis. J Vet Diagn Invest 2009, 21:197-202.
  • [26]Lehner B, Sandner B, Marschallinger J, Lehner C, Furtner T, Couillard-Despres S, Rivera FJ, Brockhoff G, Bauer HC, Weidner N, Aigner L: The dark side of BrdU in neural stem cell biology: detrimental effects on cell cycle, differentiation and survival. Cell Tissue Res 2011, 345:313-328.
  文献评价指标  
  下载次数:40次 浏览次数:22次