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1 型糖尿病患者接受干细胞教育治疗后，外周血胰岛素生成细胞（PB-IPC）上葡萄糖转运蛋白 2（GLUT2）的表达增加。

Increase in the Expression of Glucose Transporter 2 (GLUT2) on the Peripheral Blood Insulin-Producing Cells (PB-IPC) in Type 1 Diabetic Patients after Receiving Stem Cell Educator Therapy.

机构信息

Throne Biotechnologies, Paramus, NJ 07652, USA.

Fresenius Medical Care North America, Waltham, MA 02451, USA.

出版信息

Int J Mol Sci. 2024 Jul 30;25(15):8337. doi: 10.3390/ijms25158337.

DOI:10.3390/ijms25158337
PMID:39125908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11313087/
Abstract

Multicenter international clinical trials demonstrated the clinical safety and efficacy by using stem cell educator therapy to treat type 1 diabetes (T1D) and other autoimmune diseases. Previous studies characterized the peripheral blood insulin-producing cells (PB-IPC) from healthy donors with high potential to give rise to insulin-producing cells. PB-IPC displayed the molecular marker glucose transporter 2 (GLUT2), contributing to the glucose transport and sensing. To improve the clinical efficacy of stem cell educator therapy in the restoration of islet β-cell function, we explored the GLUT2 expression on PB-IPC in recent onset and longstanding T1D patients. In the Food and Drug Administration (FDA)-approved phase 2 clinical studies, patients received one treatment with the stem cell educator therapy. Peripheral blood mononuclear cells (PBMC) were isolated for flow cytometry analysis of PB-IPC and other immune markers before and after the treatment with stem cell educator therapy. Flow cytometry revealed that both recent onset and longstanding T1D patients displayed very low levels of GLUT2 on PB-IPC. After the treatment with stem cell educator therapy, the percentages of GLUT2CD45RO PB-IPC were markedly increased in these T1D subjects. Notably, we found that T1D patients shared common clinical features with patients with other autoimmune and inflammation-associated diseases, such as displaying low or no expression of GLUT2 on PB-IPC at baseline and exhibiting a high profile of the inflammatory cytokine interleukin (IL)-1β. Flow cytometry demonstrated that their GLUT2 expressions on PB-IPC were also markedly upregulated, and the levels of IL-1β-positive cells were significantly downregulated after the treatment with stem cell educator therapy. Stem cell educator therapy could upregulate the GLUT2 expression on PB-IPC and restore their function in T1D patients, leading to the improvement of clinical outcomes. The clinical data advances current understanding about the molecular mechanisms underlying the stem cell educator therapy, which can be expanded to treat patients with other autoimmune and inflammation-associated diseases.

摘要

多中心国际临床试验证明，使用干细胞教育者疗法治疗 1 型糖尿病 (T1D) 和其他自身免疫性疾病具有临床安全性和疗效。先前的研究对来自健康供体的具有产生胰岛素产生细胞高潜能的外周血胰岛素产生细胞 (PB-IPC) 进行了特征描述。PB-IPC 显示葡萄糖转运体 2 (GLUT2) 的分子标志物，有助于葡萄糖转运和感应。为了提高干细胞教育者疗法在胰岛 β 细胞功能恢复中的临床疗效，我们探索了近期发病和长期 T1D 患者 PB-IPC 上 GLUT2 的表达。在食品和药物管理局 (FDA) 批准的 2 期临床研究中，患者接受一次干细胞教育者疗法治疗。在接受干细胞教育者疗法治疗前后，分离外周血单核细胞 (PBMC) 进行 PB-IPC 和其他免疫标志物的流式细胞术分析。流式细胞术显示，近期发病和长期 T1D 患者的 PB-IPC 上 GLUT2 水平非常低。在接受干细胞教育者疗法治疗后，这些 T1D 患者的 GLUT2+CD45RO PB-IPC 百分比显着增加。值得注意的是，我们发现 T1D 患者与其他自身免疫和炎症相关疾病患者具有共同的临床特征，例如 PB-IPC 上 GLUT2 的基础表达水平低或无，并且具有高水平的炎症细胞因子白细胞介素 (IL)-1β。流式细胞术显示，他们的 PB-IPC 上 GLUT2 的表达也显着上调，并且在接受干细胞教育者疗法治疗后，IL-1β 阳性细胞的水平显着下调。干细胞教育者疗法可以上调 PB-IPC 上的 GLUT2 表达并恢复其在 T1D 患者中的功能，从而改善临床结果。这些临床数据推进了我们对干细胞教育者疗法潜在分子机制的理解，这可以扩展到治疗其他自身免疫和炎症相关疾病的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/acfbd5fbcc75/ijms-25-08337-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/6e6e892e08f8/ijms-25-08337-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/8413649dba83/ijms-25-08337-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/bacd12029185/ijms-25-08337-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/fdc825d2f8f9/ijms-25-08337-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/5a487332e5d6/ijms-25-08337-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/acfbd5fbcc75/ijms-25-08337-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/6e6e892e08f8/ijms-25-08337-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/8413649dba83/ijms-25-08337-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/bacd12029185/ijms-25-08337-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/fdc825d2f8f9/ijms-25-08337-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/5a487332e5d6/ijms-25-08337-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acba/11313087/acfbd5fbcc75/ijms-25-08337-g006.jpg

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引用本文的文献

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Clinical, Immunological, Radiographic, and Pathologic Improvements in a Patient with Long-Standing Crohn's Disease After Receiving Stem Cell Educator Therapy.

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本文引用的文献

[1]
COVID-19 and Type 1 Diabetes.

Pediatr Ann. 2024-7

[2]
Treating a type 2 diabetic patient with impaired pancreatic islet function by personalized endoderm stem cell-derived islet tissue.

Cell Discov. 2024-4-30

[3]
The glucose transporter 2 regulates CD8 T cell function via environment sensing.

Nat Metab. 2023-11

[4]
Challenges in tolerogenic dendritic cell therapy for autoimmune diseases: the route of administration.

Immunother Adv. 2023-7-18

[5]
Incidence of Diabetes in Children and Adolescents During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

JAMA Netw Open. 2023-6-1

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Int J Mol Sci. 2023-6-11

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Mol Biol Rep. 2023-8

[8]
Type 1 diabetes and risk of heart failure: A systematic review and meta-analysis.

Diabetes Res Clin Pract. 2023-8

[9]
Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes.

Cell Stem Cell. 2023-5-4

[10]
Revisiting the Pathogenesis of Type 1 Diabetes: Importance of Neural Input to Pancreatic Islets and the Therapeutic Capability of Stem Cell Educator Therapy to Restore Their Integrity.

Biomedicines. 2023-2-16

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