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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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Apoptotic BMSCs reduce grafted islets apoptosis through the holo-Lcn2/Slc22a17/Fe3+ axis.

Cuinan Lu1, Jiale Wang1, Ying Wang1

  • 1The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Stem Cell Research & Therapy
|April 11, 2026
PubMed
Summary

Apoptotic bone marrow mesenchymal stem cells (BMSCs) protect grafted islets from cell death. This protective effect is mediated by the holo-Lcn2 protein, which enhances iron transport into cells, improving islet transplantation outcomes.

Keywords:
ApoptosisBone marrow mesenchymal stem cellsIslet transplantationSlc22a17T1DMholo-Lcn2

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Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice
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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.