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Article

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

by
Yong Zhao
1,*,
Boris Veysman
1,
Kristine Antolijao
2,
Yelu Zhao
1,
Yldalina Papagni
2,
Honglan Wang
1,
Robin Ross
1,
Terri Tibbot
3,
Darinka Povrzenic
2 and
Richard Fox
1
1
Throne Biotechnologies, Paramus, NJ 07652, USA
2
Fresenius Medical Care North America, Waltham, MA 02451, USA
3
Life Line Stem Cell Tissue, Cord Blood Bank, New Haven, IN 46774, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(15), 8337; https://doi.org/10.3390/ijms25158337
Submission received: 14 June 2024 / Revised: 28 July 2024 / Accepted: 28 July 2024 / Published: 30 July 2024
(This article belongs to the Special Issue Molecular Research on Type 1 Diabetes and Its Complications)
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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 GLUT2+CD45RO+ 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.
Keywords: GLUT2; peripheral blood insulin-producing cells; cord blood-derived stem cells; stem cell educator therapy; type 1 diabetes; autoimmune diseases; IL-1β GLUT2; peripheral blood insulin-producing cells; cord blood-derived stem cells; stem cell educator therapy; type 1 diabetes; autoimmune diseases; IL-1β

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MDPI and ACS Style

Zhao, Y.; Veysman, B.; Antolijao, K.; Zhao, Y.; Papagni, Y.; Wang, H.; Ross, R.; Tibbot, T.; Povrzenic, D.; Fox, R. 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. Int. J. Mol. Sci. 2024, 25, 8337. https://doi.org/10.3390/ijms25158337

AMA Style

Zhao Y, Veysman B, Antolijao K, Zhao Y, Papagni Y, Wang H, Ross R, Tibbot T, Povrzenic D, Fox R. 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. International Journal of Molecular Sciences. 2024; 25(15):8337. https://doi.org/10.3390/ijms25158337

Chicago/Turabian Style

Zhao, Yong, Boris Veysman, Kristine Antolijao, Yelu Zhao, Yldalina Papagni, Honglan Wang, Robin Ross, Terri Tibbot, Darinka Povrzenic, and Richard Fox. 2024. "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" International Journal of Molecular Sciences 25, no. 15: 8337. https://doi.org/10.3390/ijms25158337

APA Style

Zhao, Y., Veysman, B., Antolijao, K., Zhao, Y., Papagni, Y., Wang, H., Ross, R., Tibbot, T., Povrzenic, D., & Fox, R. (2024). 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. International Journal of Molecular Sciences, 25(15), 8337. https://doi.org/10.3390/ijms25158337

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