Advertisement

Stem cell therapy for the treatment of parasitic infections: is it far away?

Abstract

Stem cell therapy is an interventional treatment that introduces new cells into damaged tissues, which help in treating many diseases and injuries. It has been proved that stem cell therapy is effective for the treatment of cancers, diabetes mellitus, Parkinson’s disease, Huntington’s disease, cardiovascular diseases, neurological disorders, and many other diseases. Recently, stem cell therapy has been introduced to treat parasitic infections. The culture supernatant of mesenchymal stem cells (MSCs) is found to inhibit activation and proliferation of macrophages induced by the soluble egg antigen of Schistosoma japonicum, and MSC treatment relieves S. japonicum-induced liver injury and fibrosis in mouse models. In addition, transplantation of MSCs into naïve mice is able to confer host resistance against malaria, and MSCs are reported to play an important role in host protective immune responses against malaria by modulating regulatory T cells. In mouse models of Chagas disease, bone marrow mononuclear cell has been shown effective in reducing inflammation and fibrosis in mice infected with Trypanosoma cruzi, and transplantation of the bone marrow mononuclear cells prevents and reverses the right ventricular dilatation induced by T. cruzi infection in mice. Preliminary clinical trials demonstrate that transplantation of bone marrow derived-cells may become an important therapeutic modality in the management of end-stage heart diseases associated with Chagas disease. Based on these exciting results, it is considered by stating that it is firmly believed that, within the next few years, we will be able to find the best animal models and the appropriate stem cell type, stem cell number, injection route, and disease state that will result in possible benefits for the patients with parasitic infections, and stem cell therapy, although at an initial stage currently, will become a real therapeutic option for parasitic diseases.

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

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 199

This is the net price. Taxes to be calculated in checkout.

References

  1. Aejaz HM, Aleem AK, Parveen N, Khaja MN, Narusu ML, Habibullah CM (2007) Stem cell therapy—present status. Transplant Proc 39:694–699

  2. Akita S, Akino K, Hirano A, Ohtsuru A, Yamashita S (2010) Mesenchymal stem cell therapy for cutaneous radiation syndrome. Health Phys 98:858–862

  3. Antoniades CA, Watts C (2013) Huntington’s disease and cell therapies: past, present, and future. Methods Mol Biol 1010:19–32

  4. Asami M, Owhashi M, Abe T, Nawa Y (1991) Susceptibility of multipotent haemopoietic stem cell deficient W/Wv mice to Plasmodium berghei-infection. Immunol Cell Biol 69:355–360

  5. Belyaev NN, Brown DE, Diaz AI, Rae A, Jarra W, Thompson J, Langhorne J, Potocnik AJ (2010) Induction of an IL7-R+c-Kithi myelolymphoid progenitor critically dependent on IFN-gamma signaling during acute malaria. Nat Immunol 11:477–485

  6. Bjorklund A, Kordower JH (2013) Cell therapy for Parkinson’s disease: what next? Mov Disord 28:110–115

  7. Bockarie MJ, Kelly-Hope LA, Rebollo M, Molyneux DH (2013) Preventive chemotherapy as a strategy for elimination of neglected tropical parasitic diseases: endgame challenges. Philos Trans R Soc Lond B Biol Sci 368:20120144

  8. Bright AT, Winzeler EA (2013) Epidemiology: resistance mapping in malaria. Nature 498:446–447

  9. Cedar SH (2006) The function of stem cells and their future roles in healthcare. Br J Nurs 15:104–107

  10. Chen Z, Qi LZ, Zeng R, Li HY, Dai LJ (2010) Stem cells and hepatic cirrhosis. Panminerva Med 52:149–165

  11. Chhabra P, Brayman KL (2013) Stem cell therapy to cure type 1 diabetes: from hype to hope. Stem Cells Transl Med 2:328–336

  12. Cioli D, Pica-Mattoccia L (2003) Praziquantel. Parasitol Res 90:S3–S9

  13. Corsten MF, Shah K (2008) Therapeutic stem-cells for cancer treatment: hopes and hurdles in tactical warfare. Lancet Oncol 9:376–384

  14. Doenhoff MJ, Cioli D, Utzinger J (2008) Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Curr Opin Infect Dis 21:659–667

  15. dos Santos RR, Soares MB, de Carvalho AC (2004) Bone marrow cells transplant in the treatment of chronic chagasic cardiomyopathy. Rev Soc Bras Med Trop 37:490–495

  16. El-Ansary M, Abdel-Aziz I, Mogawer S, Abdel-Hamid S, Hammam O, Teaema S, Wahdan M (2012) Phase II trial: undifferentiated versus differentiated autologous mesenchymal stem cells transplantation in Egyptian patients with HCV induced liver cirrhosis. Stem Cell Rev 8:972–981

  17. El-Badri N, Ghoneim MA (2013) Mesenchymal stem cell therapy in diabetes mellitus: progress and challenges. J Nucleic Acids 2013:194858

  18. Engels D, Savioli L (2006) Reconsidering the underestimated burden caused by neglected tropical diseases. Trends Parasitol 22:363–366

  19. Ferreira PE, Culleton R, Gil JP, Meshnick SR (2013) Artemisinin resistance in Plasmodium falciparum: what is it really? Trends Parasitol 29:318–320

  20. Frontera WR (2013) The Nobel Prize, stem cells, and rehabilitation. Am J Phys Med Rehabil 92:189–190

  21. Gascon J, Bern C, Pinazo MJ (2010) Chagas disease in Spain, the United States, and other non-endemic countries. Acta Trop 115:22–27

  22. Geary TG (2012) Are new anthelmintics needed to eliminate human helminthiases? Curr Opin Infect Dis 25:709–717

  23. Ghosh K, Ghosh K (2007) Pathogenesis of anemia in malaria: a concise review. Parasitol Res 101:1463–1469

  24. Goldenberg RC, Jelicks LA, Fortes FS, Weiss LM, Rocha LL, Zhao D, Carvalho AC, Spray DC, Tanowitz HB (2008) Bone marrow cell therapy ameliorates and reverses chagasic cardiomyopathy in a mouse model. J Infect Dis 197:544–547

  25. Greenwood BM, Bojang K, Whitty CJ, Targett GA (2005) Malaria. Lancet 365:1487–1498

  26. Gryseels B, Polman K, Clerinx J, Kestens L (2006) Human schistosomiasis. Lancet 368:1106–1118

  27. Guarita-Souza LC, Carvalho KA, Woitowicz V, Rebelatto C, Senegaglia A, Hansen P, Miyague N, Francisco JC, Olandoski M, Faria-Neto JR, Brofman P (2006) Simultaneous autologous transplantation of cocultured mesenchymal stem cells and skeletal myoblasts improves ventricular function in a murine model of Chagas disease. Circulation 114:I120–I124

  28. Harder A (2002) Chemotherapeutic approaches to schistosomes: current knowledge and outlook. Parasitol Res 88:395–397

  29. Hotez PJ, Bottazzi ME, Franco-Paredes C, Ault S, Periago MR (2008) The neglected tropical diseases of Latin America and the Caribbean: a review of disease burden and distribution and a roadmap for control and elimination. PLoS Negl Trop Dis 2:e300

  30. Hotez PJ, Dumonteil E, Woc-Colburn L, Serpa JA, Bezek S, Edwards MS, Hallmark CJ, Musselwhite LW, Flink BJ, Bottazzi ME (2012) Chagas disease: “The New HIV/AIDS of the Americas”. PLoS Negl Trop Dis 6:e1498

  31. Hua HY, Liang YS, Zhang Y, Wei JF, Guo HX (2010) The sensitivity of artesunate against Schistosoma japonicum decreased after 10 years of use in China. Parasitol Res 107:873–878

  32. Inoue H, Yamanaka S (2011) The use of induced pluripotent stem cells in drug development. Clin Pharmacol Ther 89(5):655–661

  33. Jasmin, Jelicks LA, Koba W, Tanowitz HB, Mendez-Otero R, de Carvalho AC C, Spray DC (2012) Mesenchymal bone marrow cell therapy in a mouse model of chagas disease. Where do the cells go? PLoS Negl Trop Dis 6:e1971

  34. Kharaziha P, Hellström PM, Noorinayer B, Farzaneh F, Aghajani K, Jafari F, Telkabadi M, Atashi A, Honardoost M, Zali MR, Soleimani M (2009) Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial. Eur J Gastroenterol Hepatol 21:1199–1205

  35. King CH (2010) Parasites and poverty: the case of schistosomiasis. Acta Trop 113:95–104

  36. Li L, Zhang Y, Li Y, Yu B, Xu Y, Zhao S, Guan Z (2008) Mesenchymal stem cell transplantation attenuates cardiac fibrosis associated with isoproterenol-induced global heart failure. Transpl Int 21:1181–1189

  37. Liu R, Dong HF, Jiang MS (2012) The sensitivity of artesunate against Schistosoma japonicum decreased after 10 years of use in China? Parasitol Res 110:1563–1564

  38. Macambira SG, Vasconcelos JF, Costa CR, Klein W, Lima RS, Guimarães P, Vidal DT, Mendez LC, Ribeiro-Dos-Santos R, Soares MB (2009) Granulocyte colony-stimulating factor treatment in chronic Chagas disease: preservation and improvement of cardiac structure and function. FASEB J 23:3843–3850

  39. Machado FS, Jelicks LA, Kirchhoff LV, Shirani J, Nagajyothi F, Mukherjee S, Nelson R, Coyle CM, Spray DC, de Carvalho AC, Guan F, Prado CM, Lisanti MP, Weiss LM, Montgomery SP, Tanowitz HB (2012) Chagas heart disease: report on recent developments. Cardiol Rev 20:53–65

  40. Markus MB (2011) The hypnozoite concept, with particular reference to malaria. Parasitol Res 108:247–252

  41. Martínez-Morales PL, Revilla A, Ocaña I, González C, Sainz P, McGuire D, Liste I (2013) Progress in stem cell therapy for major human neurological disorders. Stem Cell Rev 9:685–699

  42. Maucksch C, Vazey EM, Gordon RJ, Connor B (2013) Stem cell-based therapy for Huntington’s disease. J Cell Biochem 114:754–763

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

  44. Momin EN, Mohyeldin A, Zaidi HA, Vela G, Quiñones-Hinojosa A (2010) Mesenchymal stem cells: new approaches for the treatment of neurological diseases. Curr Stem Cell Res Ther 5:326–344

  45. Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, Boyd R, Trounson A (2009) Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol 175:303–313

  46. Nadig RR (2009) Stem cell therapy—hype or hope? A review. J Conserv Dent 12:131–138

  47. Nishimura K, Takahashi J (2013) Therapeutic application of stem cell technology toward the treatment of Parkinson’s disease. Biol Pharm Bull 36:171–175

  48. Okita K, Yamanaka S (2011) Induced pluripotent stem cells: opportunities and challenges. Philos Trans R Soc Lond B Biol Sci 366(1575):2198–2207

  49. Perin EC (2006) Stem cell therapy for cardiovascular disease. Tex Heart Inst J 33:204–208

  50. Pietronave S, Prat M (2012) Advances and applications of induced pluripotent stem cells. Can J Physiol Pharmacol 90:317–325

  51. Raghavendra K, Barik TK, Reddy BP, Sharma P, Dash AP (2011) Malaria vector control: from past to future. Parasitol Res 108:757–779

  52. Ribeiro AL, Nunes MP, Teixeira MM, Rocha MO (2012) Diagnosis and management of Chagas disease and cardiomyopathy. Nat Rev Cardiol 9:576–589

  53. Ribeiro-dos-Santos G, Verjovski-Almeida S, Leite LC (2006) Schistosomiasis—a century searching for chemotherapeutic drugs. Parasitol Res 99:505–521

  54. Ribeiro Dos Santos R, Rassi S, Feitosa G, Grecco OT, Rassi A Jr, da Cunha AB, de Carvalho VB, Guarita-Souza LC, de Oliveira W Jr, Tura BR, Soares MB, de Carvalho AC C, Chagas Arm of the MiHeart Study Investigators (2012) Cell therapy in Chagas cardiomyopathy (Chagas arm of the multicenter randomized trial of cell therapy in cardiopathies study): a multicenter randomized trial. Circulation 125:2454–2461

  55. Richter J, Franken G, Mehlhorn H, Labisch A, Häussinger D (2010) What is the evidence for the existence of Plasmodium ovale hypnozoites? Parasitol Res 107:1285–1290

  56. Rossi F, Cattaneo E (2002) Neural stem cell therapy for neurological diseases: dreams and reality. Nat Rev Neurosci 3:401–409

  57. Rountree CB, Mishra L, Willenbring H (2012) Stem cells in liver diseases and cancer: recent advances on the path to new therapies. Hepatology 55:298–306

  58. Saei AA, Ahmadian S (2009) Stem cell engineering might be protective against severe malaria. Biosci Hypoth 2:48–49

  59. Sakurai H, Yamanaka S (2011) Research for cell therapy by induced pluripotent stem cell. Nihon Rinsho 69:2114–2118

  60. Shear HL, Grinberg L, Gilman J, Fabry ME, Stamatoyannopoulos G, Goldberg DE, Nagel RL (1998) Transgenic mice expressing human fetal globin are protected from malaria by a novel mechanism. Blood 92:2520–2526

  61. Shi M, Zhang Z, Xu R, Lin H, Fu J, Zou Z, Zhang A, Shi J, Chen L, Lv S, He W, Geng H, Jin L, Liu Z, Wang FS (2012) Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients. Stem Cells Transl Med 1:725–731

  62. Soares MB, Lima RS, Rocha LL, Takyia CM, Pontes-de-Carvalho L, de Carvalho AC, Ribeiro-dos-Santos R (2004) Transplanted bone marrow cells repair heart tissue and reduce myocarditis in chronic chagasic mice. Am J Pathol 164:441–447

  63. Soares MB, Garcia S, Campos de Carvalho AC, Ribeiro dos Santos R (2007) Cellular therapy in Chagas’ disease: potential applications in patients with chronic cardiomyopathy. Regen Med 2:257–264

  64. Soares MB, Santos RR (2009) Current status and perspectives of cell therapy in Chagas disease. Mem Inst Oswaldo Cruz 104:325–332

  65. Soares MB, Lima RS, Souza BS, Vasconcelos JF, Rocha LL, Dos Santos RR, Iacobas S, Goldenberg RC, Lisanti MP, Iacobas DA, Tanowitz HB, Spray DC, Campos de Carvalho AC (2011) Reversion of gene expression alterations in hearts of mice with chronic chagasic cardiomyopathy after transplantation of bone marrow cells. Cell Cycle 10:1448–1455

  66. Steinmann P, Keiser J, Bos R, Tanner M, Utzinger J (2006) Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infect Dis 6:411–425

  67. Thakur RS, Tousif S, Awasthi V, Sanyal A, Atul PK, Punia P, Das J (2013) Mesenchymal stem cells play an important role in host protective immune responses against malaria by modulating regulatory T cells. Eur J Immunol 43:2070–2077

  68. Tibbetts MD, Samuel MA, Chang TS, Ho AC (2012) Stem cell therapy for retinal disease. Curr Opin Ophthalmol 23:226–234

  69. Trivedi P, Tray N, Nguyen T, Nigam N, Gallicano GI (2010) Mesenchymal stem cell therapy for treatment of cardiovascular disease: helping people sooner or later. Stem Cells Dev 19:1109–1120

  70. Urbina JA, Docampo R (2003) Specific chemotherapy of Chagas disease: controversies and advances. Trends Parasitol 19:495–501

  71. Vercruysse J, Levecke B, Prichard R (2012) Human soil-transmitted helminths: implications of mass drug administration. Curr Opin Infect Dis 25:703–708

  72. Vilas-Boas F, Feitosa GS, Soares MB, Pinho-Filho JA, Mota A, Almeida AJ, Carvalho C, de Carvalho HG, de Oliveira AD, dos Santos RR (2004) Bone marrow cell transplantation to the myocardium of a patient with heart failure due to Chagas’ disease. Arq Bras Cardiol 82:185–187

  73. Vilas-Boas F, Feitosa GS, Soares MB, Mota A, Pinho-Filho JA, Almeida AJ, Andrade MV, Carvalho HG, Dourado-Oliveira A, Ribeiro-dos-Santos R (2006) Early results of bone marrow cell transplantation to the myocardium of patients with heart failure due to Chagas disease. Arq Bras Cardiol 87:159–166

  74. Wang W, Wang L, Liang YS (2012) Susceptibility or resistance of praziquantel in human schistosomiasis: a review. Parasitol Res 111:1871–1877

  75. Wang W, Li HJ, Qu GL, Xing YT, Yang ZK, Dai JR, Liang YS (2013) Is there a reduced sensitivity of dihydroartemisinin against praziquantel-resistant Schistosoma japonicum? Parasitol Res. doi:10.1007/s00436-013-3647-1

  76. White NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM (2013) Malaria. Lancet. doi:10.1016/S0140-6736(13)60024-0

  77. Wilson MS, Mentink-Kane MM, Pesce JT, Ramalingam TR, Thompson R, Wynn TA (2007) Immunopathology of schistosomiasis. Immunol Cell Biol 85:148–154

  78. Wu W, Wang W, Huang YX (2011) New insight into praziquantel against various developmental stages of schistosomes. Parasitol Res 109(6):1501–1507

  79. Wu W, Huang Y (2013) Application of praziquantel in schistosomiasis japonica control strategies in China. Parasitol Res 112:909–915

  80. Xu HJ, Qian H, Zhu W, Zhang X, Yan YM, Zhang LL, Mao F, Xu WR (2011) Inhibition of culture supernatant of mesenchymal stem cells on macrophages RAW264.7 activated by soluble egg antigen of Schistosoma japonicum. Chin J Parasitol Parasit Dis 29:425–430

  81. Xu HJ, Qian H, Zhu W, Zhang X, Yan YM, Zhang LL, Mao F, Wang M, Xu HT, Xu WR (2012) Mesenchymal stem cells relieve fibrosis of Schistosoma japonicum-induced mouse liver injury. Exp Biol Med (Maywood) 237:585–592

  82. Yoshida Y, Yamanaka S (2010) Recent stem cell advances: induced pluripotent stem cells for disease modeling and stem cell-based regeneration. Circulation 122:80–87

  83. Yu Y, Lu L, Qian X, Chen N, Yao A, Pu L, Zhang F, Li X, Kong L, Sun B, Wang X (2010) Antifibrotic effect of hepatocyte growth factor-expressing mesenchymal stem cells in small-for-size liver transplant rats. Stem Cells Dev 19:903–914

  84. Zhu X, He B, Zhou X, Ren J (2013) Effects of transplanted bone-marrow-derived mesenchymal stem cells in animal models of acute hepatitis. Cell Tissue Res 351:477–486

Download references

Acknowledgments

This study received financial supports from the National Science and Technology Pillar Program of China (grant no. 2009BAI78B06) and Jiangsu Provincial Government Overseas Scholarship.

Author information

Correspondence to Yong-Jun Rui or Wei Wang.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zhang, Y., Mi, J., Rui, Y. et al. Stem cell therapy for the treatment of parasitic infections: is it far away?. Parasitol Res 113, 607–612 (2014) doi:10.1007/s00436-013-3689-4

Download citation

Keywords

  • Malaria
  • Schistosomiasis
  • Stem Cell Therapy
  • Praziquantel
  • Bone Marrow Mononuclear Cell