Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights
Abstract A large body of evidence suggests that mesenchymal stromal cells (MSCs) are able to respond rapidly to the cytokine milieu following systemic infusion. This encounter has the potential to dictate their therapeutic efficacy (also referred to as licensing). MSCs are able to rapidly react to c...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-025-04158-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1825197622554525696 |
|---|---|
| author | Akram Hoseinzadeh Seyed-Alireza Esmaeili Reza Sahebi Anahita Madani Melak Mahmoud Mahmoudi Maliheh Hasannia Rasoul Baharlou |
| author_facet | Akram Hoseinzadeh Seyed-Alireza Esmaeili Reza Sahebi Anahita Madani Melak Mahmoud Mahmoudi Maliheh Hasannia Rasoul Baharlou |
| author_sort | Akram Hoseinzadeh |
| collection | DOAJ |
| description | Abstract A large body of evidence suggests that mesenchymal stromal cells (MSCs) are able to respond rapidly to the cytokine milieu following systemic infusion. This encounter has the potential to dictate their therapeutic efficacy (also referred to as licensing). MSCs are able to rapidly react to cellular damage by migrating to the inflamed tissue and ultimately modifying the inflammatory microenvironment. However, the limited use of MSCs in clinical practice can be attributed to a lack of understanding of the fate of MSCs in patients after administration and long term MSC-derived therapeutic activity. While the known physiological effectors of viable MSCs make a relative contribution, an innate property of MSCs as a therapeutic agent is their caspase-dependent cell death. These mechanisms may be involving the functional reprogramming of myeloid phagocytes via efferocytosis, the process by which apoptotic bodies (ABs) are identified for engulfment by both specialized and non-specialized phagocytic cells. Recent studies have provided evidence that the uptake of ABs with a distinct genetic component can induce changes in gene expression through the process of epigenetic remodeling. This phenomenon, known as ‘trained immunity’, has a significant impact on immunometabolism processes. It is hypothesized that the diversity of recipient cells within the inflammatory stroma adjacent to MSCs may potentially serve as a biomarker for predicting the clinical outcome of MSC treatment, while also contributing to the variable outcomes observed with MSC-based therapies. Therefore, the long-term reconstructive process of MSCs may potentially be mediated by MSC apoptosis and subsequent phagocyte-mediated efferocytosis. Graphical Abstract |
| format | Article |
| id | doaj-art-753fcb2a7620409386ae97d6c1875060 |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-753fcb2a7620409386ae97d6c18750602025-02-09T12:15:34ZengBMCStem Cell Research & Therapy1757-65122025-02-0116112910.1186/s13287-025-04158-zFate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insightsAkram Hoseinzadeh0Seyed-Alireza Esmaeili1Reza Sahebi2Anahita Madani Melak3Mahmoud Mahmoudi4Maliheh Hasannia5Rasoul Baharlou6Department of Immunology, Faculty of Medicine, Semnan University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Mashhad University of Medical SciencesDepartment of Modern Sciences and Technologies, Mashhad University of Medical SciencesDepartment of Biology, Kavian Institute of Higher educationDepartment of Immunology, Faculty of Medicine, Mashhad University of Medical SciencesCancer Research Center, Faculty of Medicine, Semnan University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Semnan University of Medical SciencesAbstract A large body of evidence suggests that mesenchymal stromal cells (MSCs) are able to respond rapidly to the cytokine milieu following systemic infusion. This encounter has the potential to dictate their therapeutic efficacy (also referred to as licensing). MSCs are able to rapidly react to cellular damage by migrating to the inflamed tissue and ultimately modifying the inflammatory microenvironment. However, the limited use of MSCs in clinical practice can be attributed to a lack of understanding of the fate of MSCs in patients after administration and long term MSC-derived therapeutic activity. While the known physiological effectors of viable MSCs make a relative contribution, an innate property of MSCs as a therapeutic agent is their caspase-dependent cell death. These mechanisms may be involving the functional reprogramming of myeloid phagocytes via efferocytosis, the process by which apoptotic bodies (ABs) are identified for engulfment by both specialized and non-specialized phagocytic cells. Recent studies have provided evidence that the uptake of ABs with a distinct genetic component can induce changes in gene expression through the process of epigenetic remodeling. This phenomenon, known as ‘trained immunity’, has a significant impact on immunometabolism processes. It is hypothesized that the diversity of recipient cells within the inflammatory stroma adjacent to MSCs may potentially serve as a biomarker for predicting the clinical outcome of MSC treatment, while also contributing to the variable outcomes observed with MSC-based therapies. Therefore, the long-term reconstructive process of MSCs may potentially be mediated by MSC apoptosis and subsequent phagocyte-mediated efferocytosis. Graphical Abstracthttps://doi.org/10.1186/s13287-025-04158-zMesenchymal stem cellsApoptosisEfferocytosisApoptotic bodiesLong-term effectivenessImmunoregulation |
| spellingShingle | Akram Hoseinzadeh Seyed-Alireza Esmaeili Reza Sahebi Anahita Madani Melak Mahmoud Mahmoudi Maliheh Hasannia Rasoul Baharlou Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights Stem Cell Research & Therapy Mesenchymal stem cells Apoptosis Efferocytosis Apoptotic bodies Long-term effectiveness Immunoregulation |
| title | Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights |
| title_full | Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights |
| title_fullStr | Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights |
| title_full_unstemmed | Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights |
| title_short | Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights |
| title_sort | fate and long lasting therapeutic effects of mesenchymal stromal stem like cells mechanistic insights |
| topic | Mesenchymal stem cells Apoptosis Efferocytosis Apoptotic bodies Long-term effectiveness Immunoregulation |
| url | https://doi.org/10.1186/s13287-025-04158-z |
| work_keys_str_mv | AT akramhoseinzadeh fateandlonglastingtherapeuticeffectsofmesenchymalstromalstemlikecellsmechanisticinsights AT seyedalirezaesmaeili fateandlonglastingtherapeuticeffectsofmesenchymalstromalstemlikecellsmechanisticinsights AT rezasahebi fateandlonglastingtherapeuticeffectsofmesenchymalstromalstemlikecellsmechanisticinsights AT anahitamadanimelak fateandlonglastingtherapeuticeffectsofmesenchymalstromalstemlikecellsmechanisticinsights AT mahmoudmahmoudi fateandlonglastingtherapeuticeffectsofmesenchymalstromalstemlikecellsmechanisticinsights AT malihehhasannia fateandlonglastingtherapeuticeffectsofmesenchymalstromalstemlikecellsmechanisticinsights AT rasoulbaharlou fateandlonglastingtherapeuticeffectsofmesenchymalstromalstemlikecellsmechanisticinsights |