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by claude@2026-07, 2026-07-03
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This paper studied whether extracellular vesicles released by adipose-derived mesenchymal stem cells (AD-MSC-EVs) reproduce previously observed immunomodulatory effects against Leishmania amazonensis infection in C57BL/6 mice, using in vitro macrophage assays and an in vivo cutaneous infection model. AD-MSC-EVs were purified and characterized, and in vitro they reduced parasite load when added 4 hours post-infection via reactive oxygen species induction, independent of nitric oxide, whereas adding them 24 hours post-infection did not reproduce the effect; in vivo, intralesional AD-MSC-EVs reduced lesion size but did not alter parasite load and decreased Leishmania-specific IgM/IgG while lowering proinflammatory cytokine production and CD8⁺ cytotoxicity, with increased IL-10 production by γδ T cells. A major limitation stated by the authors is that lesion control depended on IL-10, as AD-MSC-EVs failed in IL-10–deficient mice. Relevance to endometriosis: the study does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Leishmaniasis, a neglected tropical disease caused by protozoa of the Leishmania genus, is characterized by an imbalanced immune response that promotes parasite survival while inducing tissue damage. We previously showed that adipose-derived mesenchymal stem cells (AD-MSCs) limited lesion progression in C57BL/6 mice infected with Leishmania amazonensis . In the current study, we examined whether extracellular vesicles released by AD-MSCs (AD-MSC-EVs) reproduce these therapeutic effects. AD-MSC-EVs were purified, expanded, and characterized, confirming their typical morphology and EV-associated surface markers. In vitro , treatment of infected macrophages with AD-MSC-EVs 4 hours post-infection reduced parasite load through the induction of reactive oxygen species (ROS), independent of nitric oxide (NO). However, treatment 24 hours post-infection failed to reproduce this effect. In vivo , intralesional administration of AD-MSC-EVs significantly reduced lesion size without altering parasite load, while also decreasing levels of specific IgM and IgG for Leishmania amazonensis antigens. AD-MSC-EV therapy also reduced proinflammatory cytokines production by CD4⁺ and cytotoxicity CD8⁺ T cells, while increasing IL-10 production by γδ T cells. Moreover, combined therapy with pentavalent antimonial further reduced lesion size but did not affect parasite load. Notably, AD-MSC-EVs failed to control lesions in IL-10–deficient mice, suggesting that their therapeutic effect is dependent on IL-10. In conclusion, these findings showed that AD-MSC-EVs modulated the host immune response to attenuate L. amazonensis –induced cutaneous pathology and may represent a promising adjunct or alternative therapy for cutaneous leishmaniasis. Significance Statement Cutaneous leishmaniasis is a neglected tropical disease with limited therapeutic options and significant immunopathology. This study demonstrates that extracellular vesicles derived from adipose-derived mesenchymal stem cells (AD-MSC-EVs) can modulate host immune responses and reduce lesion severity in Leishmania amazonensis infection. Rather than directly eliminating parasites, AD-MSC-EVs attenuate tissue damage through IL-10 dependent immunoregulation, highlighting a novel host-directed therapeutic strategy. These findings advance understanding of EV-mediated immune modulation and support AD-MSC-EVs as a promising adjunct or alternative approach for treating cutaneous leishmaniasis and potentially other inflammatory infectious diseases.
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Abstract
Leishmaniasis, a neglected tropical disease caused by protozoa of the Leishmania genus, is characterized by an imbalanced immune response that promotes parasite survival while inducing tissue damage. We previously showed that adipose-derived mesenchymal stem cells (AD-MSCs) limited lesion progression in C57BL/6 mice infected with Leishmania amazonensis. In the current study, we examined whether extracellular vesicles released by AD-MSCs (AD-MSC-EVs) reproduce these therapeutic effects. AD-MSC-EVs were purified, expanded, and characterized, confirming their typical morphology and EV-associated surface markers. In vitro, treatment of infected macrophages with AD-MSC-EVs 4 hours post-infection reduced parasite load through the induction of reactive oxygen species (ROS), independent of nitric oxide (NO). However, treatment 24 hours post-infection failed to reproduce this effect. In vivo, intralesional administration of AD-MSC-EVs significantly reduced lesion size without altering parasite load, while also decreasing levels of specific IgM and IgG for Leishmania amazonensis antigens. AD-MSC-EV therapy also reduced proinflammatory cytokines production by CD4⁺ and cytotoxicity CD8⁺ T cells, while increasing IL-10 production by γδ T cells. Moreover, combined therapy with pentavalent antimonial further reduced lesion size but did not affect parasite load. Notably, AD-MSC-EVs failed to control lesions in IL-10–deficient mice, suggesting that their therapeutic effect is dependent on IL-10. In conclusion, these findings showed that AD-MSC-EVs modulated the host immune response to attenuate L. amazonensis–induced cutaneous pathology and may represent a promising adjunct or alternative therapy for cutaneous leishmaniasis.
Significance Statement Cutaneous leishmaniasis is a neglected tropical disease with limited therapeutic options and significant immunopathology. This study demonstrates that extracellular vesicles derived from adipose-derived mesenchymal stem cells (AD-MSC-EVs) can modulate host immune responses and reduce lesion severity in Leishmania amazonensis infection. Rather than directly eliminating parasites, AD-MSC-EVs attenuate tissue damage through IL-10 dependent immunoregulation, highlighting a novel host-directed therapeutic strategy. These findings advance understanding of EV-mediated immune modulation and support AD-MSC-EVs as a promising adjunct or alternative approach for treating cutaneous leishmaniasis and potentially other inflammatory infectious diseases.
Competing Interest Statement
The authors have declared no competing interest.
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