Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
June-2014 Volume 33 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2014 Volume 33 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin‑induced diabetes in miniature pigs: Real‑time tracing with MRI in vivo

  • Authors:
    • Kuanxiao Tang
    • Xiaoyan Xiao
    • Dayue Liu
    • Yunfeng Shen
    • Yingming Chen
    • Yu Wang
    • Baoying Li
    • Fei Yu
    • Dedong Ma
    • Jinhua Yan
    • Hua Liang
    • Daizhi Yang
    • Jianping Weng
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Vascular Surgery and Radiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
    Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1469-1476
    |
    Published online on: April 7, 2014
       https://doi.org/10.3892/ijmm.2014.1729
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Cellular replacement therapy for diabetes mellitus (DM) has received much attention. In this study, we investigated the effect of transplantation of autologous bone marrow‑derived mesenchymal stem cells (ABMSCs) in streptozotocin (STZ)‑induced diabetic miniature pigs. Miniature pig BMSCs were cultured, labeled with superparamagnetic iron oxide (SPIO) and transplanted into the pancreas of diabetic miniature pigs through targeted intervention. Blood glucose levels, intravenous and oral glucose tolerance test (OGTT), serum insulin, C‑peptide and islets histology were analyzed. These transplanted cells were then identified by magnetic resonance imaging (MRI). The results showed that transplantation of ABMSCs reversed STZ‑induced diabetes in miniature pigs. Blood glucose levels, intravenous, OGTT, serum insulin and C‑peptide were significantly recovered in the diabetic minipigs with the autologous BMSC (DMAB) transplantation group. In addition, the number of islets was significantly increased in this group compared to the diabetic minipig control (DMC) group with conventional therapy. These data suggested the implantation of autologous BMSCs for type 1 diabetes treatment can partially restore the function of islet β cells and maintain blood glucose homeostasis. Transplanted autologous BMSCs may improve islet repairing by differentiating for new islets and change pancreatic microcirculation and be identified in a real‑time manner using MRI in vivo.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Haller MJ, Viener HL, Wasserfall C, Brusko T, Atkinson MA and Schatz DA: Autologous umbilical cord blood infusion for type 1 diabetes. Exp Hematol. 36:710–715. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Limbert C, Päth G, Jakob F and Seufert J: Beta-cell replacement and regeneration: strategies of cell-based therapy for type 1 diabetes mellitus. Diabetes Res Clin Pract. 79:389–399. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Hussain MA and Theise ND: Stem-cell therapy for diabetes mellitus. Lancet. 364:203–205. 2004. View Article : Google Scholar

4 

Jurewicz M, Yang S, Augello A, et al: Congenic mesenchymal stem cell therapy reverses hyperglycemia in experimental type 1 diabetes. Diabetes. 59:3139–3147. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Zhao Y, Jiang Z, Zhao T, et al: Reversal of type 1 diabetes via islet β cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med. 10:32012.

6 

Tang DQ, Cao LZ, Burkhardt BR, Xia CQ, Litherland SA, Atkinson MA and Yang LJ: In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes. 53:1721–1732. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Ianus A, Holz GG, Theise ND and Hussain MA: In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest. 111:843–850. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Lee RH, Seo MJ, Reger RL, Spees JL, Pulin AA, Olson SD and Prockop DJ: Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice. Proc Natl Acad Sci USA. 103:17438–17443. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Gao X, Song L, Shen K, Wang H, Niu W and Qin X: Transplantation of bone marrow derived cells promotes pancreatic islet repair in diabetic mice. Biochem Biophys Res Commun. 371:132–137. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Hasegawa Y, Ogihara T, Yamada T, et al: Bone marrow (BM) transplantation promotes beta-cell regeneration after acute injury through BM cell mobilization. Endocrinology. 148:2006–2015. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Urbán VS, Kiss J, Kovács J, Gócza E, Vas V, Monostori E and Uher F: Mesenchymal stem cells cooperate with bone marrow cells in therapy of diabetes. Stem Cells. 26:244–253. 2008.PubMed/NCBI

12 

Couri CE and Voltarelli JC: Autologous stem cell transplantation for early type 1 diabetes mellitus. Autoimmunity. 41:666–672. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Larsen MO, Wilken M, Gotfredsen CF, Carr RD, Svendsen O and Rolin B: Mild streptozotocin diabetes in the Göttingen minipig. A novel model of moderate insulin deficiency and diabetes. Am J Physiol Endocrinol Metab. 282:E1342–E1351. 2002.

14 

Larsen MO, Rolin B, Wilken M, Carr RD and Gotfredsen CF: Measurements of insulin secretory capacity and glucose tolerance to predict pancreatic beta-cell mass in vivo in the nicotinamide/streptozotocin Göttingen minipig, a model of moderate insulin deficiency and diabetes. Diabetes. 52:118–123. 2003.PubMed/NCBI

15 

Hara H, Lin YJ, Zhu X, et al: Safe induction of diabetes by high-dose streptozotocin in pigs. Pancreas. 36:31–38. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Wen Y, Ouyang J, Yang R, Chen J, Liu Y, Zhou X and Burt RK: Reversal of new-onset type 1 diabetes in mice by syngeneic bone marrow transplantation. Biochem Biophys Res Commun. 374:282–287. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Ezquer FE, Ezquer ME, Parrau DB, Carpio D, Yañez AJ and Conget PA: Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type 1 diabetic mice. Biol Blood Marrow Transplant. 14:631–640. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Chang C, Niu D, Zhou H, Zhang Y, Li F and Gong F: Mesenchymal stroma cells improve hyperglycemia and insulin deficiency in the diabetic porcine pancreatic microenvironment. Cytotherapy. 10:796–805. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Olmos PR and Borzone G: Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 302:624author reply 624–625. 2009. View Article : Google Scholar

20 

Couri CE, Oliveira MC, Stracieri AB, et al: C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 301:1573–1579. 2009. View Article : Google Scholar

21 

Scolding N, Marks D and Rice C: Autologous mesenchymal bone marrow stem cells: practical considerations. J Neurol Sci. 265:111–115. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Yamout B, Hourani R, Salti H, et al: Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: a pilot study. J Neuroimmunol. 227:185–189. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Jirák D1, Kríz J, Herynek V, et al: MRI of transplanted pancreatic islets. Magn Reson Med. 52:1228–1233. 2004.

24 

Neri M, Maderna C, Cavazzin C, et al: Efficient in vitro labeling of human neural precursor cells with superparamagnetic iron oxide particles: relevance for in vivo cell tracking. Stem Cells. 26:505–516. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Amsalem Y, Mardor Y, Feinberg MS, et al: Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium. Circulation. 116(Suppl 11): I38–I45. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Murray HE, Paget MB, Bailey CJ and Downing R: Sustained insulin secretory response in human islets co-cultured with pancreatic duct-derived epithelial cells within a rotational cell culture system. Diabetologia. 52:477–485. 2009. View Article : Google Scholar

27 

Lipsett M, Aikin R, Castellarin M, Hanley S, Jamal AM, Laganiere S and Rosenberg L: Islet neogenesis: a potential therapeutic tool in type 1 diabetes. Int J Biochem Cell Biol. 38:498–503. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Jeong JO, Kim MO, Kim H, et al: Dual angiogenic and neurotrophic effects of bone marrow-derived endothelial progenitor cells on diabetic neuropathy. Circulation. 119:699–708. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Shibata T, Naruse K, Kamiya H, et al: Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats. Diabetes. 57:3099–3107. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Kin T, Korbutt GS, Kobayashi T, Dufour JM and Rajotte RV: Reversal of diabetes in pancreatectomized pigs after transplantation of neonatal porcine islets. Diabetes. 54:1032–1039. 2005. View Article : Google Scholar

31 

Tang KX, Yan JH, Shen YF, et al: Tracing type 1 diabetic Tibet miniature pig’s bone marrow mesenchymal stem cells in vitro by magnetic resonance imaging. J Diabetes. 6:123–131. 2014.PubMed/NCBI

32 

Layton DS, Strom AD, O’Neil TE, et al: Development of an anti-porcine CD34 monoclonal antibody that identifies hematopoietic stem cells. Exp Hematol. 35:171–178. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Nir T, Melton DA and Dor Y: Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 117:2553–2561. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Alvarez SS, Jimenez LM, Murillo AZ, et al: A new approach for bone marrow-derived stem cells intrapancreatic autotransplantation in diabetic rats. Microsurgery. 26:539–542. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Frank JA, Miller BR, Arbab AS, et al: Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology. 228:480–487. 2003. View Article : Google Scholar

36 

Barnett BP, Arepally A, Karmarkar PV, et al: Magnetic resonance-guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells. Nat Med. 13:986–991. 2007. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Tang K, Xiao X, Liu D, Shen Y, Chen Y, Wang Y, Li B, Yu F, Ma D, Yan J, Yan J, et al: Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin‑induced diabetes in miniature pigs: Real‑time tracing with MRI in vivo. Int J Mol Med 33: 1469-1476, 2014.
APA
Tang, K., Xiao, X., Liu, D., Shen, Y., Chen, Y., Wang, Y. ... Weng, J. (2014). Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin‑induced diabetes in miniature pigs: Real‑time tracing with MRI in vivo. International Journal of Molecular Medicine, 33, 1469-1476. https://doi.org/10.3892/ijmm.2014.1729
MLA
Tang, K., Xiao, X., Liu, D., Shen, Y., Chen, Y., Wang, Y., Li, B., Yu, F., Ma, D., Yan, J., Liang, H., Yang, D., Weng, J."Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin‑induced diabetes in miniature pigs: Real‑time tracing with MRI in vivo". International Journal of Molecular Medicine 33.6 (2014): 1469-1476.
Chicago
Tang, K., Xiao, X., Liu, D., Shen, Y., Chen, Y., Wang, Y., Li, B., Yu, F., Ma, D., Yan, J., Liang, H., Yang, D., Weng, J."Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin‑induced diabetes in miniature pigs: Real‑time tracing with MRI in vivo". International Journal of Molecular Medicine 33, no. 6 (2014): 1469-1476. https://doi.org/10.3892/ijmm.2014.1729
Copy and paste a formatted citation
x
Spandidos Publications style
Tang K, Xiao X, Liu D, Shen Y, Chen Y, Wang Y, Li B, Yu F, Ma D, Yan J, Yan J, et al: Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin‑induced diabetes in miniature pigs: Real‑time tracing with MRI in vivo. Int J Mol Med 33: 1469-1476, 2014.
APA
Tang, K., Xiao, X., Liu, D., Shen, Y., Chen, Y., Wang, Y. ... Weng, J. (2014). Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin‑induced diabetes in miniature pigs: Real‑time tracing with MRI in vivo. International Journal of Molecular Medicine, 33, 1469-1476. https://doi.org/10.3892/ijmm.2014.1729
MLA
Tang, K., Xiao, X., Liu, D., Shen, Y., Chen, Y., Wang, Y., Li, B., Yu, F., Ma, D., Yan, J., Liang, H., Yang, D., Weng, J."Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin‑induced diabetes in miniature pigs: Real‑time tracing with MRI in vivo". International Journal of Molecular Medicine 33.6 (2014): 1469-1476.
Chicago
Tang, K., Xiao, X., Liu, D., Shen, Y., Chen, Y., Wang, Y., Li, B., Yu, F., Ma, D., Yan, J., Liang, H., Yang, D., Weng, J."Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin‑induced diabetes in miniature pigs: Real‑time tracing with MRI in vivo". International Journal of Molecular Medicine 33, no. 6 (2014): 1469-1476. https://doi.org/10.3892/ijmm.2014.1729
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team