Stem Cell Research & Therapy, 18 April 2026
Research Background
Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus that can progress to end-stage renal disease. Although standard treatments with corticosteroids and immunosuppressive agents have improved patient outcomes, a subset of patients remains non-responsive and is classified as refractory, carrying a high risk of disease progression. In this context, mesenchymal stem cells (MSCs), particularly umbilical cord-derived MSCs (UC-MSCs), have emerged as a promising immunomodulatory therapy.
Methods
This study was designed as a real-world observational study to evaluate the efficacy and safety of umbilical cord-derived mesenchymal stem cell (UC-MSC) infusion in patients with refractory lupus nephritis.
Study Population
A total of 120 patients were enrolled at Nanjing Drum Tower Hospital between 2009 and 2022. All patients:
- Met the 1997 ACR classification criteria for systemic lupus erythematosus
- Had lupus nephritis defined by proteinuria (>0.5 g/24 h), abnormal urinary sediment, or renal biopsy findings
- Were classified as refractory after failing to respond to at least one standard immunosuppressive regimen (cyclophosphamide, mycophenolate mofetil, tacrolimus, leflunomide, or azathioprine) for ≥6 months
Exclusion criteria included severe multi-organ failure, pregnancy or lactation, and follow-up duration <12 months.
UC-MSC Preparation and Quality Control
Allogeneic UC-MSCs were produced under Good Manufacturing Practice (GMP) conditions from umbilical cords of healthy donors:
- Umbilical cord tissue was minced (~1 mm²) and cultured in DMEM-LG supplemented with 10% FBS
- Cells were expanded to 80–85% confluence before harvesting
- Quality control included:
- Cell viability >92%
- Negative screening for microbial contamination and viruses (HBV, HCV, HIV, CMV, syphilis)
- Immunophenotype: CD29+, CD44+, CD105+, CD166+; negative for CD34, CD45, HLA-DR
- Confirmation of osteogenic and adipogenic differentiation in vitro
Cell Infusion Protocol
- Dose: 1–2 × 10⁶ cells/kg body weight
- Prophylaxis: aspirin or clopidogrel initiated 1 day before infusion and continued for 14 days
- Premedication: intravenous dexamethasone 5 mg administered 30 minutes prior to infusion
- Post-infusion: maintenance of low-dose corticosteroids and baseline immunosuppressive therapy
Some patients received repeated infusions (up to 4 times within 12 months) depending on response or relapse risk.
Data Collection and Follow-up
Patients were evaluated at baseline and at 3, 6, and 12 months. Data collected included:
- Clinical parameters: age, sex, disease duration, SLEDAI-2000 score
- Laboratory tests: 24-hour proteinuria, serum albumin, creatinine, eGFR, complement levels (C3, C4), autoantibodies
- Treatment data: prednisone dosage and prior immunosuppressive therapies
- Adverse events: infusion reactions, infections, thrombosis, malignancy, and mortality
Outcome Measures
- Primary outcomes:
- Renal response (complete or partial)
- Relapse rate
- Definitions:
- Complete response (CR): proteinuria <0.5 g/24 h, albumin ≥35 g/L, stable eGFR
- Partial response (PR): ≥50% reduction in proteinuria and <3 g/24 h, albumin >30 g/L
- Relapse: increase in proteinuria or ≥25% decline in eGFR
- Secondary outcomes: changes in proteinuria, albumin, eGFR, and corticosteroid dosage
Main Results
After 12 months of treatment:
- The cumulative renal response rate reached 56.7%
- The relapse rate remained low (8.8%)
- Proteinuria significantly decreased (from 3.2 to 1.2 g/24 h)
- Serum albumin increased markedly
- Prednisone dosage was reduced from 20 mg/day to 10 mg/day
Notably:
- Patients with baseline eGFR ≥45 ml/min/1.73 m² had a significantly higher response rate (66.3% vs. 34.4%)
- Baseline eGFR ≥45 was identified as an independent predictor of treatment response
Safety
- No serious adverse events were reported
- Acute infusion-related events were rare (~2.1%)
- The 12-month infection rate was 10.9%, mostly mild to moderate
These findings indicate a favorable safety profile for UC-MSC therapy.
Scientific Interpretation
UC-MSCs exert multi-faceted mechanisms of action:
- Modulation of immune balance (Treg/Th17)
- Inhibition of B-cell activation
- Promotion of renal tissue repair
Therapeutic efficacy strongly depends on baseline renal function. In earlier stages (eGFR ≥45), preserved renal tissue allows for greater regenerative potential and optimal MSC activity.
Conclusion and Clinical Implications
Umbilical cord-derived MSC therapy:
- Is effective and safe for treating refractory lupus nephritis
- Improves renal function, reduces proteinuria, and decreases corticosteroid dependence
- Shows optimal efficacy in patients without advanced renal impairment
This study supports UC-MSCs as a next-generation immunomodulatory therapy. However, randomized, multicenter clinical trials are still required to validate and standardize its clinical application.
References
Zheng, Y., Liu, S., Zeng, L., Luo, Y., Jin, Z., Yang, D., … & Sun, L. (2026). Allogeneic umbilical cord-derived mesenchymal stromal cells for treatment of refractory lupus nephritis: a real-world study. Stem Cell Research & Therapy
Source: Stem Cell Research & Therapy
Link: https://doi.org/10.1186/ s13287-026-05021-5
