Evelyn Orevaoghene Onosakponome¹*, Robinson Ndifrekeabasi Itek²

¹Department of Medical Microbiology and Parasitology, Federal University Otuoke, Bayelsa State, Nigeria
²Department of Medical Microbiology and Parasitology, Rivers State University, Nigeria

*Corresponding Author: Evelyn Orevaoghene Onosakponome, Department of Medical Microbiology and Parasitology, Federal University Otuoke, Bayelsa State, Nigeria.

Received: June 15, 2026; Published: July 24, 2026

Chronic parasitic infections constitute a persistent global health burden affecting over one billion individuals, with disproportionate impact in low and middle-income countries. Conventional antiparasitic therapeutics effectively reduce parasite prevalence but fail to reverse established tissue pathology including hepatic cirrhosis, myocardial fibrosis, and neurological damage. Mesenchymal stem cell (MSC) therapy has garnered increasing attention as a potential host-directed regenerative strategy addressing tissue repair and immune dysregulation in parasitic disease contexts. This comprehensive review synthesises preclinical evidence across schistosomiasis, Chagas disease, leishmaniasis, malaria-associated organ complications, and neurocysticercosis, alongside limited clinical observations from cardiac applications. Preclinical investigations consistently demonstrate anti-inflammatory and anti-fibrotic effects through paracrine signalling and direct cellular differentiation. Critical evaluation reveals substantial heterogeneity in evidence quality, marked methodological limitations including short-term follow-up periods, inadequate parasite burden assessment, and absence of standardised disease models. Human clinical evidence remains minimal outside early uncontrolled cardiac trials with severe design limitations. Significant barriers to clinical translation include unresolved parasite-immune-stem cell interactions, insufficient long-term safety documentation in human populations, prohibitive manufacturing costs precluding access in endemic regions, and inadequate regulatory frameworks in countries bearing greatest disease burden. Future progress requires standardised preclinical models, properly designed human trials, elucidation of optimal combination therapy approaches, and international investment in regulatory capacity building in endemic nations. Current evidence position supports continued investigation but does not justify clinical translation beyond carefully controlled research settings.

Keywords: Chronic Parasitic Diseases; Mesenchymal Stem Cells; Stem Cell Therapy; Tissue Fibrosis; Translational Barriers

References

1. World Health Organization. “Neglected tropical diseases”. Geneva: WHO (2023).
2. McManus DP., et al. “Schistosomiasis”. Nature Reviews Disease Primers 4 (2018): 13.
3. Ribeiro AL., et al. “Diagnosis and management of Chagas disease”. Nature Reviews Cardiology10 (2012): 576-589.
4. Steverding D. “The history of leishmaniasis”. Parasit Vectors1 (2021): 82.
5. Ndimubanzi PC., et al. “A systematic review of the frequency of neurocysticercosis with a focus on people with epilepsy”. PLOS Neglected Tropical Diseases11 (2016): e870.
6. Carod-Artal FJ. “Neurological complications of Schistosoma infection”. Transactions of the Royal Society of Tropical Medicine and Hygiene2 (2008): 107-116.
7. Vos T., et al. “Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013”. Lancet 9995 (2015): 743-800.
8. Ponzo E., et al. “Insights into the epidemiology, pathogenesis, and differential diagnosis of schistosomiasis”. European Journal of Microbiology and Immunology2 (2024).
9. Verjee MA. “Schistosomiasis: Still a Cause of Significant Morbidity and Mortality”. Research and Reports in Tropical Medicine 10 (2020): 153-163.
10. Cioli D., et al. “Schistosomiasis control: praziquantel forever?” Molecular and Biochemical Parasitology1 (2014): 23-29.
11. Rassi A., et al. “Chagas disease”. Lancet9723 (2010): 1388-1402.
12. Sundar S., et al. “Single-Dose Liposomal Amphotericin B for Visceral Leishmaniasis in India”. The New England Journal of Medicine6 (2010): 504-512.
13. Pittenger MF., et al. “Mesenchymal stem cell perspective: cell biology to clinical progress”. NPJ Regen Medicine1 (2019): 22.
14. Uccelli A., et al. “MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis”. Trials1 (2019).
15. Mohammad Saeed Kahrizi., et al. “Recent advances in pre-conditioned mesenchymal stem/stromal cell (MSCs) therapy in organ failure; a comprehensive review of preclinical studies”. Stem Cell Research and Therapy1 (2023).
16. Colley DG., et al. “Human schistosomiasis”. Lancet9936 (2014): 2253-2264.
17. Pearce EJ., et al. “Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni”. Journal of Experimental Medicine1 (1991): 159-166.
18. Wynn TA and Barron L. “Macrophages: master regulators of inflammation and fibrosis”. Seminar on Liver Disease3 (2010): 245-257.
19. Carson JP., et al. “Schistosome-Induced Fibrotic Disease: The Role of Hepatic Stellate Cells”. Trends in Parasitology 6 (2018): 524-540.
20. Biernacka A., et al. “TGF-β signaling in fibrosis”. Growth Factors5 (2011): 196-202.
21. Gincberg G., et al. “Neural stem cells: therapeutic potential for neurodegenerative diseases”. British Medical Bulletin 1 (2012): 7-19.
22. Hochberg NS and Montgomery SP. “Chagas Disease”. Annals of Internal Medicine2 (2023): ITC17-ITC32.
23. Laucella SA., et al. “Frequency of Interferon‐γ–Producing T Cells Specific for Trypanosoma cruzi Inversely Correlates with Disease Severity in Chronic Human Chagas Disease”. Journal of Infectious Disease 5 (2004): 909-918.
24. Soulaidopoulos S., et al. “Inflammatory Mechanisms in Myocarditis—Recent Therapeutic Strategies”. Biomolecules10 (2025): 1475.
25. Thomas TP and Grisanti LA. “The Dynamic Interplay Between Cardiac Inflammation and Fibrosis”. Frontiers in Physiology 11 (2020): 529075.
26. Alexander J and Brombacher F. “T helper1/t helper2 cells and resistance/susceptibility to leishmania infection: is this paradigm still relevant?”. Frontiers in Immunology 3 (2012): 80.
27. Kumar R and Nylén S. “Immunobiology of visceral leishmaniasis”. Frontiers in Immunology 3 (2012): 251.
28. Yadav P., et al. “Symptoms and Diagnosis of Visceral Leishmaniasis and Post-kala-azar Dermal Leishmaniasis”. In: Visceral Leishmaniasis and Post-Kala-Azar Dermal Leishmaniasis (2025): 90-97.
29. Foroutan M., et al. “Mesenchymal Stem Cells: A Double-Edged Approach for Managing Cutaneous Leishmaniasis Lesions”. International Wound Journal6 (2025): e70709.
30. White MT., et al. “Plasmodium vivax and Plasmodium falciparum infection dynamics: re-infections, recrudescences and relapses”. Malaria Journal1 (2018).
31. Snider CJ., et al. “Recurrent Plasmodium falciparum malaria infections in Kenyan children diminish T-cell immunity to Epstein Barr virus lytic but not latent antigens”. PLoS One3 (2012): e31753.
32. Madkhali A. “Adhesion analysis of different PfEMP1 variants to CD36, ICAM-1 and primary endothelial cells [dissertation]”. Liverpool: University of Liverpool (2022).
33. Milner DA., et al. “The systemic pathology of cerebral malaria in African children”. Frontiers in Cellular and Infection Microbiology 4 (2014): 104.
34. Garcia HH., et al. “Clinical symptoms, diagnosis, and treatment of neurocysticercosis”. Lancet Neurology12 (2014): 1202-1215.
35. Mattei V., et al. “Validated methods for isolation and qualification of mesenchymal stromal/stem cells from different sources”. Journal of Translational Medicine1 (2025).
36. Müller L., et al. “Immunomodulatory Properties of Mesenchymal Stromal Cells: An Update”. Frontiers in Cell and Developmental Biology 9 (2021): 637725.
37. Machado CdeV., et al. “Immunological characteristics of mesenchymal stem cells”. Revista Brasileira de Hematologia e Hemoterapia 1 (2013): 62-67.
38. Li J., et al. “The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy”. Stem Cell Research and Therapy1 (2023).
39. Chen S., et al. “Unveiling heterogeneity in MSCs: exploring marker-based strategies for defining MSC subpopulations”. Journal of Translational Medicine1 (2024).
40. Zhou T., et al. “Challenges and advances in clinical applications of mesenchymal stromal cells”. Journal of Hematology and Oncology1 (2021).
41. Chen W. “TGF-β Regulation of T Cells”. Annual Reviews Immunology1 (2023).
42. Chen Z., et al. “The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells”. Chiniese Journal of Traumatology1 (2023): 1-10.
43. Chan JA., et al. “Surface antigens of Plasmodium falciparum-infected erythrocytes as immune targets and malaria vaccine candidates”. Cell Molecular Life Sciences19 (2014): 3633-3657.
44. Palomino-Cano C., et al. “Targeting and activation of macrophages in leishmaniasis. A focus on iron oxide nanoparticles”. Frontiers in Immunology 15 (2024): 1437430.
45. Ramos TD., et al. “Combined therapy with adipose tissue-derived mesenchymal stromal cells and meglumine antimoniate controls lesion development in murine cutaneous leishmaniasis”. Stem Cell Research and Therapy 11 (2020): 374.
46. Zheng G., et al. “Mesenchymal stromal cell-derived extracellular vesicles: regenerative and immunomodulatory effects and potential applications in sepsis”. Cell Tissue Research1 (2018): 1-15.
47. Wu T., et al. “MSC-Derived Extracellular Vesicles: Roles and Molecular Mechanisms for Tissue Repair”. International Journal of Nanomedicine 20 (2025): 7953-7974.
48. Dong L., et al. “hUCMSC-extracellular vesicles downregulated hepatic stellate cell activation and reduced liver injury in S. japonicum-infected mice”. Stem Cell Research and Therapy 11 (1 (2020).
49. Théry C., et al. “Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines”. Journal of Extracell Vesicles1 (2018): 1535750.
50. Song J., et al. “Multiplexed strategies toward clinical translation of extracellular vesicles”. Theranostics 15 (2022): 6740-6761.
51. Li Z., et al. “Advancements in extracellular vesicles biomanufacturing: a comprehensive overview of large-scale production and clinical research”. Frontiers in Bioengineering and Biotechnology 13 (2025): 1487627.
52. El-Mahdi MM., et al. “Ameliorative effect of bone marrow-derived stem cells on injured liver of mice infected with Schistosoma mansoni”. Korean Journal of Parasitology2 (2014): 151-162.
53. Hegab MH., et al. “Therapeutic potential effect of bone marrow-derived mesenchymal stem cells on chronic liver disease in murine Schistosomiasis Mansoni”. Journal of Parasitology Disease2 (2018): 277-286.
54. Hammam OA., et al. “Wharton’s jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni-induced liver fibrosis”. Scientific Report 6 (2016): 21005.
55. Fu CL., et al. “A novel mouse model of Schistosoma haematobium egg-induced immunopathology”. PLoS Pathogen5 (2012): e1002605.
56. Mentink–Kane MM., et al. “Accelerated and progressive and lethal liver fibrosis in mice that lack interleukin (IL)-10, IL-12p40, and IL-13Rα2”. Gastroenterology6 (2011): 2200-2209.
57. Franco KGS., et al. “Association of IL-9, IL-10, and IL-17 cytokines with hepatic fibrosis in human Schistosoma mansoni infection”. Frontiers in Immunology 12 (2021): 779534.
58. Dibo N., et al. “Pattern recognition receptor signaling and innate immune responses to schistosome infection”. Frontiers in Cellular and Infection Microbiology 12 (2022): 1040270.
59. Fikry H., et al. “Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver injury induced by Schistosoma mansoni: A histological study”. International Journal of Stem Cells1 (2016): 96-106.
60. Chen JY., et al. “Immunometabolism: Towards a better understanding the mechanism of parasitic infection and immunity”. Frontiers in Immunology 12 (2021): 661241.
61. Maciel PS., et al. “Schistosoma mansoni infection is impacted by malnutrition”. Frontiers in Microbiology 12 (2021): 635843.
62. Ellakany AR., et al. “Stem cell-derived exosomes as a potential therapy for schistosomal hepatic fibrosis in experimental animals”. Pathogen Global Health (2023): 1-21.
63. Zhong H., et al. “Sja-let-7 suppresses the development of liver fibrosis via Schistosoma japonicum extracellular vesicles”. PLoS Pathogen 20 (4 (2024): e1012153.
64. Angeles JMaM., et al. “Behind Enemy Lines: Immunomodulatory Armamentarium of the Schistosome Parasite”. Frontiers in Immunology 11 (2020): 1018.
65. Efared B., et al. “Urinary bladder Schistosoma haematobium-related squamous cell carcinoma: a report of two fatal cases and literature review”. Tropical Diseases, Travel Medicine and Vaccines1 (2022).
66. Simões H., et al. “Liver damage in schistosomiasis is reduced by adipose tissue-derived stem cell therapy after praziquantel treatment”. PLOS Neglected Tropical Diseases8 (2020): e0008635.
67. Santos LL., et al. “Urogenital Schistosomiasis—History, Pathogenesis, and Bladder Cancer”. Journal of Clinical Medicine2 (2021): 205.
68. Sadr S., et al. “Anti-inflammatory and immunomodulatory effects of mesenchymal stem cell therapy on parasitic drug resistance”. Expert Review of Anti-infective Therapy6 (2024): 435-451.
69. Souza MC., et al. “Mesenchymal stromal cell therapy attenuated lung and kidney injury but not brain damage in experimental cerebral malaria”. Stem Cell Research and Therapy 6 (2015): 102.
70. Hackam DG, Redelmeier DA. Translation of research evidence from animals to humans”. JAMA 14 (2006): 1731-1732.
71. Contopoulos-Ioannidis DG., et al. “Translation of highly promising basic science research into clinical applications”. American Journal of Medicine6 (2003): 477-488.
72. Bahari M., et al. “Stem Cell Therapy, the Market, the Opportunities and the Threat”. International Journal of Molecular and Cellular Medicine3 (2023): 310-319.
73. Muraca M., et al. “Diverging Concepts and Novel Perspectives in Regenerative Medicine”. International Journal of Molecular Science5 (2017): 1021.
74. Vaishnav M. “The Indian regulatory framework and the surge of unproven stem cell therapies—a call for diagnosis”. Journal of Law Bioscience2 (2025).
75. Master Z., et al. “Unproven stem cell interventions: A global public health problem requiring global deliberation”. Stem Cell Reports6 (2021): 1435-1445.

Citation

Citation: Evelyn Orevaoghene Onosakponome and Robinson Ndifrekeabasi Itek. “Stem Cell Therapy in the Management of Chronic Parasitic Diseases: Current Evidence, Methodological Limitations, and Future Therapeutic Prospects". Acta Scientific Medical Sciences 10.8 (2026): 39-54.

Copyright

Copyright: © 2026 Evelyn Orevaoghene Onosakponome and Robinson Ndifrekeabasi Itek. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.