Apoptotic BMSCs reduce grafted islets apoptosis through the holo-Lcn2/Slc22a17/Fe³⁺ axis

Area of Science:

• Cell Biology
• Immunology
• Regenerative Medicine

Background:

• Early apoptosis of grafted islets is a major obstacle in islet transplantation, limiting its long-term success.
• Bone marrow mesenchymal stem cells (BMSCs) have immunomodulatory properties that may protect transplanted islets.

Purpose of the Study:

• To investigate the protective effects of apoptotic BMSCs on islet cell apoptosis and improve islet transplantation outcomes.
• To elucidate the underlying molecular mechanisms, particularly the role of secreted factors from apoptotic BMSCs.

Main Methods:

• Bone marrow mesenchymal stem cells (BMSCs) were induced into apoptosis using Staurosporine.
• Conditioned medium from apoptotic BMSCs was used to pretreat β cells and in vivo islet transplantation models.
• Proteomic analysis was performed to identify key secreted proteins.
• Inhibition of specific molecular pathways (e.g., iron transport) was used to confirm mechanisms.

Main Results:

• Pretreatment with conditioned medium from apoptotic BMSCs significantly suppressed β cell apoptosis.
• Co-transplantation of islets with apoptotic BMSCs in diabetic rats improved islet survival and transplantation efficacy.
• Proteomic analysis identified holo-Lcn2 as a key anti-apoptotic factor secreted by apoptotic BMSCs.
• The anti-apoptotic effect of holo-Lcn2 was dependent on its interaction with the Slc22a17 transporter and Fe³⁺ transport.

Conclusions:

• Apoptotic BMSCs protect grafted islets from apoptosis via the holo-Lcn2/Slc22a17/Fe³⁺ axis.
• This mechanism enhances islet transplantation outcomes in a preclinical model.
• BMSCs-based acellular therapies hold promise for improving islet transplantation efficacy.