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Updated: Jan 10, 2026
Assessment of the Immunomodulatory Properties of Human Mesenchymal Stem Cells MSCs
Published on: December 24, 2015
Rejuvenation of mesenchymal stem cells by human peripheral blood lymphocytes
Yi Luo1,2, Xin-Xin Zhu1,3, Qing-Rong Le1,3
1Institute of Medicinal Biotechnology & Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China.
Background:
In the in vitro expansion of mesenchymal stem cells (MSCs), replicative or stress-induced senescence poses a significant challenge, leading to the loss of their cellular properties and therapeutic functions. Currently, there is a lack of efficient strategies to address this issue.
Results:
Here we presented a novel approach to combat cellular senescence and promote cell proliferation by coculturing human MSCs with human peripheral blood lymphocytes (PBLs). In a heterogeneous population of MSCs comprising both aged and nonaged cells, PBL effector cells, rather than their cytokines, exhibited a dual role. They selectively induced apoptosis in aged cells by facilitating p53 SUMOylation and activating the p53-dependent mitochondrial pathway, while simultaneously safeguarding younger cells against senescence and promoting cell proliferation by activating Serpinb2/NF-κB signaling. This resulted in a decrease in aged MSCs and an enrichment of rejuvenated MSCs. This process effectively reversed the senescence phenotype, leading to the remodeling of stemness characteristics and the enhancement of functionality within the MSC population. Furthermore, MSCs rejuvenated by PBLs presented an enhanced therapeutic efficacy and a favorable safety profile.
Conclusions:
PBLs rejuvenate MSCs by promptly removing aged cells and enhancing the stemness and proliferative capacity of nonaged cells. This work provides an ideal method for obtaining substantial MSCs while meeting the quality requirements for stem cell therapy.
Insights
Human peripheral blood lymphocytes (PBLs) rejuvenate mesenchymal stem cells (MSCs) by eliminating aged cells and enhancing younger MSCs. This novel method combats senescence, improving MSCs for therapeutic applications.
Area of Science:
- Stem Cell Biology
- Immunology
- Cellular Senescence
Background:
- Mesenchymal stem cells (MSCs) lose therapeutic properties due to senescence during in vitro expansion.
- Current strategies to combat MSC senescence are inefficient.
Purpose of the Study:
- To develop an efficient method to combat MSC senescence and enhance cell proliferation.
- To investigate the role of human peripheral blood lymphocytes (PBLs) in MSC rejuvenation.
Main Methods:
- Coculturing human MSCs with human PBLs.
- Analyzing the effects of PBLs on aged and non-aged MSCs.
- Investigating molecular pathways involved in MSC senescence and proliferation.
Main Results:
- PBLs selectively induced apoptosis in aged MSCs via p53 SUMOylation and mitochondrial pathways.
- PBLs promoted proliferation of younger MSCs by activating Serpinb2/NF-κB signaling.
- This process rejuvenated MSCs, restoring stemness and enhancing therapeutic efficacy.
Conclusions:
- PBLs effectively rejuvenate MSCs by removing aged cells and enhancing younger cells.
- This method provides a substantial number of high-quality MSCs for stem cell therapy.
- PBL-mediated rejuvenation enhances MSC therapeutic efficacy and safety.
