Background Bone marrow-derived cell (BMDC) transplantation is increasingly recognized as a valuable strategy in regenerative therapies. However, the data regarding the impact of BMDC transplantation on the severity of diabetes mellitus type 1 (DMT1). Aim This study aimed to determine the effectiveness of adoptive transfer of BMDC isolated from either non-diabetic mice (nBMDC) or diabetic mice (dBMDC) in the treatment of a DMT1 mouse model. Methods Male Swiss albino mice underwent a 16-hour fasting period, followed by administration of streptozotocin (STZ) at a dose of 40 mg/kg body weight for five days to induce DMT1. After 14 days, diabetic mice were divided into four groups. The first group served as a diabetic control and received sodium citrate buffer, while the remaining three groups were treated for two weeks with one of the following: subcutaneous (s.c.) administration of insulin (8 U/kg/day), intravenous (i.v.) inoculation of nBMDCs (1 × 106 cells/mouse/once), or i.v. injections of dBMDC (1 × 106 cells/mouse/once). Results STZ-induced DMT1 mice treated with either nBMDC or dBMDC exhibited a noticeable increase in the expression of CD4+ T lymphocytes, CD8+ T lymphocytes, and NK lymphocytes, myeloid granulocytic neutrophil (CD11b+/Ly-6G+ cells), monocytic macrophage (CD11b+/Ly-6G− cells), and monocytic CD11b+/Ly-6G− cells. Additionally, there was a marked reduction in the percentages of CD25+ T cells, Foxp3+ cells, regulatory T cells (Tregs), CD25+/Foxp3+ cells, Treg CD25+/Foxp3− cells, Treg CD4+/CD25+ cells, and Treg CD4+/CD25− cells within the myeloid cell population in the spleen. The therapeutic efficacy of BMDC as an anti-diabetic therapy was further supported by a significant reduction in the proportion of early and late apoptosis in splenic leukocytes, accompanied by a slight increase in necrosis in STZ-induced DMT1 mice receiving either nBMDC or dBMDC. Conclusion In summary, adoptive transfer of BMDCs exerts significant immunomodulatory and anti-apoptotic effects on pancreatic β cells, which are beneficial for pancreatic islets in DMT1 mice. Clinical studies are warranted to evaluate the safety and effectiveness of the adoptive transfer of BMDCs as a potential therapy for autoimmune DMT1.

Efficiency of bone marrow-derived cells in the treatment of experimental autoimmune type 1 diabetes: immunomodulatory and anti-apoptotic properties

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2026年4月25日

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Mohamed Nassef,
Amira Hafez,
Soha Gomaa

摘要

Background

Bone marrow-derived cell (BMDC) transplantation is increasingly recognized as a valuable strategy in regenerative therapies. However, the data regarding the impact of BMDC transplantation on the severity of diabetes mellitus type 1 (DMT1).

Aim

This study aimed to determine the effectiveness of adoptive transfer of BMDC isolated from either non-diabetic mice (nBMDC) or diabetic mice (dBMDC) in the treatment of a DMT1 mouse model.

Methods

Male Swiss albino mice underwent a 16-hour fasting period, followed by administration of streptozotocin (STZ) at a dose of 40 mg/kg body weight for five days to induce DMT1. After 14 days, diabetic mice were divided into four groups. The first group served as a diabetic control and received sodium citrate buffer, while the remaining three groups were treated for two weeks with one of the following: subcutaneous (s.c.) administration of insulin (8 U/kg/day), intravenous (i.v.) inoculation of nBMDCs (1 × 10⁶ cells/mouse/once), or i.v. injections of dBMDC (1 × 10⁶ cells/mouse/once).

Results

STZ-induced DMT1 mice treated with either nBMDC or dBMDC exhibited a noticeable increase in the expression of CD4⁺ T lymphocytes, CD8⁺ T lymphocytes, and NK lymphocytes, myeloid granulocytic neutrophil (CD11b⁺/Ly-6G⁺ cells), monocytic macrophage (CD11b⁺/Ly-6G⁻ cells), and monocytic CD11b⁺/Ly-6G⁻ cells. Additionally, there was a marked reduction in the percentages of CD25⁺ T cells, Foxp3⁺ cells, regulatory T cells (Tregs), CD25⁺/Foxp₃⁺ cells, Treg CD25⁺/Foxp3⁻ cells, Treg CD4⁺/CD25⁺ cells, and Treg CD4⁺/CD25⁻ cells within the myeloid cell population in the spleen. The therapeutic efficacy of BMDC as an anti-diabetic therapy was further supported by a significant reduction in the proportion of early and late apoptosis in splenic leukocytes, accompanied by a slight increase in necrosis in STZ-induced DMT1 mice receiving either nBMDC or dBMDC.

Conclusion

In summary, adoptive transfer of BMDCs exerts significant immunomodulatory and anti-apoptotic effects on pancreatic β cells, which are beneficial for pancreatic islets in DMT1 mice. Clinical studies are warranted to evaluate the safety and effectiveness of the adoptive transfer of BMDCs as a potential therapy for autoimmune DMT1.