Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cell Therapy in Diabetic Nephropathy Patients: A Clinical Trial

Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus and a leading cause of end-stage renal disease worldwide. Despite current standard therapies, many patients continue to experience progressive decline in renal function. As inflammation and immune dysregulation are increasingly recognized as contributors to DN pathogenesis, novel therapeutic strategies targeting these mechanisms are being explored.

Mesenchymal stem cells (MSCs), particularly those derived from umbilical cord tissue, have shown promising anti-inflammatory and regenerative effects in preclinical studies of kidney disease. Their immunomodulatory properties, low immunogenicity, and ease of collection make them a compelling option for cell-based therapies.

This clinical trial aims to evaluate the safety and potential therapeutic benefit of allogeneic umbilical cord-derived MSCs administered via intra-renal injection in individuals with diabetic nephropathy. The study is designed to provide early human data on the feasibility of using UC-MSCs as an adjunctive therapy in DN management. By assessing changes in renal function and inflammatory biomarkers over time, the trial seeks to explore the biological impact of UC-MSC therapy in this population.

This research represents an important step toward developing cell-based interventions for chronic kidney disease, particularly in settings where conventional treatments are insufficient. The findings are expected to contribute valuable data to the growing field of regenerative nephrology.

• Umbilical Cord Mesenchymal Stem Cells (Biological): This intervention consists of a single intra-renal injection of allogeneic umbilical cord-derived mesenchymal stem cells (UC-MSCs) administered under imaging guidance. The dose administered is 1 × 10⁶ cells per kilogram of body weight.

Primary outcomes

• Incidence of Adverse Events and Serious Adverse Events [From baseline up to 12 months post-injection]: Safety is assessed by recording the number and percentage of participants experiencing any adverse events (AEs), including both local and systemic reactions.

Secondary outcomes

• Change in Estimated Glomerular Filtration Rate (eGFR) [Baseline and at 1, 3, 6, 9, and 12 months after treatment]: Calculated using the CKD-EPI 2021 formula
• Change in Serum Creatinine [Baseline and at 1, 3, 6, 9, and 12 months after treatment]: Measured in mg/dL. Collected via venous blood samples
• Change in Urine Albumin-to-Creatinine Ratio (UACR) [Baseline and at 1, 3, 6, 9, and 12 months after treatment]: Measured in mg/g from morning spot urine samples

Other outcomes

• Change in Serum TNF-α Levels [Baseline and at 1, 3, 6, 9, and 12 months after treatment]: Tumor necrosis factor-alpha (TNF-α) is measured in patient serum using ELISA as a marker of systemic inflammation. The change in TNF-α concentration from baseline over 12 months will be analyzed to evaluate the immunomodulatory effect of UC-MSC therapy.
• Change in Serum IL-10 Levels [Baseline and at 1, 3, 6, 9, and 12 months after treatment]: Interleukin-10 (IL-10) is measured in patient serum using ELISA as an anti-inflammatory cytokine. This outcome assesses whether UC-MSC treatment modulates IL-10 levels over a 12-month follow-up period.

Sex: All, ages: 30 Years to 65 Years

Inclusion Criteria:

* Diagnosed with Type 2 Diabetes Mellitus (T2DM)
* Aged between 40 and 65 years
* Diagnosed with chronic kidney disease (CKD) stage III or IV, defined as estimated GFR (eGFR) between 15-60 mL/min/1.73 m² (using CKD-EPI formula)
* Renal biopsy showing diabetic nephropathy type IIa-IV
* Presence of proteinuria, with urine albumin-to-creatinine ratio (UACR) between 30-3000 mg/g (spot morning urine sample)
* Controlled diabetes, defined as HbA1c <10.0% during screening
* Blood pressure within the range of: Systolic 100-160 mmHg, Diastolic 60-100 mmHg
* On stable standard therapy for diabetic nephropathy (e.g. ACE inhibitors or ARBs) for at least 12 weeks prior to screening
* Willing to provide written informed consent and comply with all study procedures until completion

Exclusion Criteria:

* Active malignancy or history of cancer
* Active liver disease or abnormal liver function (ALT or AST ≥2× upper limit of normal)
* Hemoglobin <8 g/dL or platelet count <100,000/µL
* Serious or unstable cerebrovascular or cardiovascular conditions within the last 6 months
* Positive pregnancy test or currently breastfeeding (for women of reproductive age)
* Currently receiving immunosuppressive therapy equivalent to ≥20 mg/day prednisone
* History of participation in other stem cell research or therapy studies