Safety and efficacy of allogeneic umbilical cord-derived mesenchymal stem cell transplantation in type 2 diabetes: a pilot clinical trial

Ramin Raoufinia; Jalil Tavakol-Afshari; Mozhgan Afkhamizadeh; Ehsan Saburi; Amir Adhami Moghadam; Sareh Etemad; Hamid Reza Rahimi

doi:10.62347/OPHF7871

Safety and efficacy of allogeneic umbilical cord-derived mesenchymal stem cell transplantation in type 2 diabetes: a pilot clinical trial

Am J Stem Cells. 2025 Oct 15;14(4):244-260. doi: 10.62347/OPHF7871. eCollection 2025.

Authors

Ramin Raoufinia^{1

2}, Jalil Tavakol-Afshari³, Mozhgan Afkhamizadeh⁴, Ehsan Saburi¹, Amir Adhami Moghadam⁵, Sareh Etemad⁶, Hamid Reza Rahimi^{1

7}

Affiliations

¹ Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences Mashhad, Iran.
² Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences Neyshabur, Iran.
³ Department of Immunology, Faculty of Medicine, BuAli Research Institute, Mashhad University of Medical Sciences Mashhad, Iran.
⁴ Metabolic Syndrome Research Center, Mashhad University of Medical Sciences Mashhad, Iran.
⁵ Department of Internal Medicine and Critical Care, Islamic Azad University, Mashhad Branch Mashhad, Iran.
⁶ Department of Pathology, Faculty of Anatomical Pathology, Ghaem Hospital, University of Medicine Mashhad, Iran.
⁷ Medical Genetics Research Center, Mashhad University of Medical Sciences Mashhad, Iran.

Abstract

Background: Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction, with chronic inflammation playing a central pathogenic role. Mesenchymal stem cells (MSCs) possess therapeutic potential through immunomodulatory and tissue-reparative properties. This study aimed to evaluate the safety and efficacy of intravenous allogeneic umbilical cord-derived MSCs (UC-MSCs) in patients with T2DM.

Methods: Eleven adults with T2DM (disease duration ≥ 10 years; HbA1c ≤ 8%) received a single intravenous infusion of 1 × 10⁸ UC-MSCs. This open-label pilot trial assessed safety (adverse events, hematologic and metabolic parameters) and efficacy (glycemic control and inflammatory gene expression) over a 2-month follow-up period. UC-MSCs were isolated under standardized conditions.

Results: UC-MSC transplantation in patients with T2DM was well tolerated, with only transient fever (36.3%) and mild muscle pain (18.2%) reported. The intervention resulted in significant metabolic improvements, including a 2.1% reduction in HbA1c (P = 0.00095) and a decrease in fasting glucose by 93.7 mg/dL (P = 0.00097). Treatment also modulated inflammatory pathways, as evidenced by upregulating of IKBα (1.76-fold, P = 0.0067) and downregulating of TNFα (0.62-fold) and IL-6 (0.65-fold). Variability in IKBα expression accounted for 48% of the variance in HbA1c (r = -0.69). Two distinct response patterns were observed: improvement in insulin sensitivity (7/11) via NF-κB suppression, and enhancement of β-cell function (3/11).

Conclusion: Allogeneic UC-MSC transplantation appears safe and significantly improves glycemic control in patients with T2DM. The heterogeneity in patient responses underscores the importance of stratification based on inflammatory status. These findings support UC-MSC therapy as a promising disease-modifying strategy and highlight the need for larger, controlled clinical trials.

Keywords: NF-κB pathway; Type 2 diabetes; cell therapy; clinical trial; gene expression; inflammation; insulin resistance; mesenchymal stem cells; umbilical cord.