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Updated: Jul 1, 2025
Assessment of the Immunomodulatory Properties of Human Mesenchymal Stem Cells MSCs
Published on: December 24, 2015
Exploring the Impact of Leishmania Major on Mesenchymal Stem Cells: Evaluating Differentiation, and Immunomodulatory
Elham Mashayekh1, Arezou Khosrojerdi2, Ahmad Zavaran Hosseini3
11 Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. elhammashayekh1372@gmail.com.
Abstract:
Pathogen recognition receptors (PRRs), which play a crucial role in responding to pathogens, affect the function of mesenchymal stem cells (MSCs). One important group of PRRs is the toll-like receptors (TLRs). When PRRs are activated, they can alter the expression of specific surface markers, the ability of MSCs to differentiate, and the types of substances they secrete. These modifications in MSC function may have unexpected consequences for patients. In this study, we examined how Leishmania major (L. major) promastigotes affect the properties of MSCs. MSCs were isolated from adipose tissue and categorized into two groups: one group left untreated and the other group exposed to L. major. Giemsa staining was employed to accurately quantify the number of parasites that entered the cells. After 72 hours, real-time polymerase chain reaction was utilized to assess the expression of TLRs. Additionally, the flow cytometry technique was used to evaluate the expression of surface markers on the MSCs. Our results showed that MSCs can engulf parasites and increase the expression of TLR4 and TLR6. The pro-inflammatory cytokine increased, and the transforming growth factor-β decreased significantly. The parasite exposure increased reactive oxygen species production. Additionally, the percentage of cluster differentiation (CD) 73 decreased, and the mean fluorescent index of CD29 and CD73 was down-regulated by L. major. Exposure to parasites diminishes the immunomodulatory capacity of MSCs. This discovery holds significance for the application of MSCs in addressing parasite infections and underscores the need for additional research to enhance their therapeutic effectiveness.
Insights
Mesenchymal stem cells (MSCs) engulf Leishmania major parasites, increasing toll-like receptor (TLR) expression and reactive oxygen species. This exposure diminishes MSCs' immunomodulatory capacity, impacting their therapeutic use in parasitic infections.
Area of Science:
- Immunology
- Stem Cell Biology
- Parasitology
Background:
- Pathogen recognition receptors (PRRs), including toll-like receptors (TLRs), modulate mesenchymal stem cell (MSC) functions.
- PRR activation can alter MSC surface markers, differentiation potential, and secreted factors, potentially affecting therapeutic outcomes.
- The impact of Leishmania major (L. major) infection on MSC properties requires detailed investigation.
Purpose of the Study:
- To investigate the effects of L. major promastigotes on the functional characteristics of adipose tissue-derived MSCs.
- To analyze changes in TLR expression, surface marker profiles, and cytokine secretion following parasite exposure.
- To assess the implications of these alterations on the immunomodulatory capacity of MSCs.
Main Methods:
- Isolation and culture of adipose tissue-derived MSCs.
- Exposure of MSCs to L. major promastigotes and quantification of parasite engulfment via Giemsa staining.
- Assessment of TLR and surface marker expression using real-time PCR and flow cytometry.
- Measurement of reactive oxygen species and cytokine levels.
Main Results:
- MSCs successfully engulfed L. major parasites.
- Increased expression of TLR4 and TLR6 was observed in MSCs post-exposure.
- Pro-inflammatory cytokine levels rose, while transforming growth factor-β decreased.
- Parasite exposure led to elevated reactive oxygen species production and down-regulation of CD29 and CD73 surface markers.
Conclusions:
- L. major infection significantly alters MSC phenotype and function, including increased TLR expression and reduced immunomodulatory capacity.
- These changes, particularly the diminished ability to modulate immune responses, have critical implications for the therapeutic application of MSCs in leishmaniasis.
- Further research is warranted to understand and potentially mitigate these effects for improved MSC-based therapies against parasitic diseases.
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