• Achievement of Complete Renal Response (CR) at Study Endpoint [ Time Frame: 12 months ]
  Proportion of Patients that achieve CR criteria including: 1) Urinary Protein:Creatinine (UPC) ratio < 0.5; 2) estimated Glomerular Filtration Rate (GFR) ≥ 120 ml/min/m2, or at least 80% of baseline; 3) urinalysis < 10 red blood cells (RBC) and no RBC casts per high power field; 4) Prednisone dose ≤10 mg/day.
• Achievement of Partial Renal Response (PR) at Study Endpoint [ Time Frame: 12 months ]
  Proportion of Patients that achieve PR criteria including: 1) reduction of UPC ratio to at least 50% of baseline; 2) estimated GFR ≥120 ml/min/m2, or at least 80% of baseline; 3) Prednisone dose ≤10 mg/day.
• Treatment Failure [ Time Frame: 24 weeks and 12 months ]
  Proportion of Patients that fulfill any of the following criteria for Treatment Failure including: 1) Daily Prednisone dose cannot be reduced ≤ 10 mg at week 24; 2) Daily Prednisone is increased above 10 mg after week 24; 3) Introduction of a new immunosuppressive regimen, not included in the trial; 4) Use of Rituximab prior to month 12.
• Response of SLE Responder Index (SRI). [ Time Frame: 12 months ]
  Proportion of Patients that achieve SRI response, defined as a >4-point reduction in the SELENA-SLEDAI score, no new British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new BILAG B score, with no worsening in physician's global assessment score versus baseline). The Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) is employed for this calculation.(SELENA-SLEDAI score). The SELENA-SLEDAI score addresses 24 descriptors in 9 organ-systems. Disease worsening increases the score that ranges from 0-105. The BILAG addresses 97 items in organ-system domains, in an ordinal (A-E) scale, converted to a numerical (0-96) scale for usual calculations.
• Selena Sledai [ Time Frame: 12 months ]
  Average change in Selena Sledai Score in patients and controls
• BILAG score [ Time Frame: 12 months ]
  Average hange in BILAG score in patients and controls
• Disease Flares [ Time Frame: 12 months ]
  Proportion of patients that experience flares as defined in the Selena Flare Index (SFI). Mild/Moderate Flares are defined by change of 3 or more points in the SELENA-SLEDAI score. Severe Flares are defined as an increase in the SELENA-SLEDAI score to more than 12 points
• Biomarker Response [ Time Frame: 24 weeks and 12 months ]
  Changes in the levels of disease relevant biomarkers in peripheral blood/plasma, including 1) anti-dsDNA antibodies by ELISA; 2) complement proteins C3/C4 by nephelometry (mg/dL); 3) Percentage of CD4+ T helper cell subpopulations (Th1, Th17, Treg) and 4) B cell subpopulations (Naive, Memory, Transitional) by Flow cytometry; and 5) Cytokine Panel by Luminex, including Tumor Necrosis Factor (TNF) alpha, Transforming Growth Factor (TGF) Beta1, Interleukin (lL) 6, IL-17A, IL-10, B-cell activating factor/B Lymphocyte Stimulator (BAFF/BLys), Monocyte chemoattractant protein-1 (MCP-1/CCL2), C-X-C motif chemokine 10 (CXCL10), Interferon (IFN) gamma.

• Lupus Erythematosus, Systemic
• Lupus Glomerulonephritis

• Biological: MSC treatment
  Umbilical cord-derived Mesenchymal Stromal Cell
  Other Name: Cellistem ® Lupus
• Drug: Standard of Care
  Methylprednisolone; Cyclophosphamide; Prednisone; Mycophenolate
  Other Name: Standard of Care for Lupus Nephritis
• Drug: Placebo
  MSC infusion vehicle
  Other Name: Placebo (for MSC)

• Experimental: MSC treatment
  Intervention: a previously selected dose of MSCs (Phase IIa) will be administered by i.v. infusion at baseline and 6 months of follow-up (total 12 months), to patients with Severe Renal SLE subject also to Standard of Care treatment with Methylprednisolone and Cyclophosphamide followed by Mycophenolate.
  Interventions:

  • Biological: MSC treatment
  • Drug: Standard of Care
• Placebo Comparator: Placebo
  Intervention: A Placebo (infusion vehicle) will be administered by i.v. infusion at baseline and 6 months of follow-up (total 12 months), to patients with Severe Renal SLE subject also to Standard of Care treatment with Methylprednisolone and Cyclophosphamide followed by Mycophenolate.
  Interventions:

  • Drug: Standard of Care
  • Drug: Placebo

Inclusion Criteria:

• Fulfilling 1997 updated American College of Rheumatology (ACR) Criteria or 2012 SLICC Classification Criteria for SLE
• Seropositive for antinuclear (≥1:80) and/or anti-DNA antibodies
• Fulfilling following criteria for active renal disease:

Class III or IV proliferative disease (ISN/RPS) Renal Biopsy within 12 months plus...

Active Urinary Sediment (> 5 red blood cells/high-power field and/or >8 white blood cells/high-power field and/or cylindruria during the current flare).

UPC ratio ≥ 1

Exclusion Criteria:

• Estimated GFR < 40ml/min/m2
• Addition during prior 3 months of randomization of: Bolus methylprednisolone or new immunosuppressive drug or intravenous immunoglobulin (IVIG) or Plasmapheresis.
• Addition during prior 6 months of randomization of Cyclophosphamide
• Addition during prior 12 months of randomization of Biological anti-B cell therapy
• Coexisting uncontrolled morbidity; Pregnancy or planned Pregnancy within next 12 months; uncontrolled infection or neoplastic disease. Pending unresolved surgical indication.