Safety of allogeneic bone marrow derived mesenchymal stromal cell therapy in renal transplant recipients: the neptune study

Abstract

BackgroundMesenchymal stromal cells (MSC) may serve as an attractive therapy in renal transplantation due to their immunosuppressive and reparative properties. While most studies have used autologous MSCs, allogeneic MSCs offer the advantage of immediate availability for clinical use. This is of major importance for indications where instant treatment is needed, for example allograft rejection or calcineurin inhibitor toxicity. Clinical studies using allogeneic MSCs are limited in number. Although these studies showed no adverse reactions, allogeneic MSCs could possibly elicit an anti-donor immune response, which may increase the incidence of rejection and impact the allograft survival in the long term. These safety issues should be addressed before further studies are planned with allogeneic MSCs in the solid organ transplant setting.Methods/design10 renal allograft recipients, 18–75 years old, will be included in this clinical phase Ib, open label, single center study. Patients will receive two doses of 1.5 × 106 per/kg body weight allogeneic bone marrow derived MSCs intravenously, at 25 and 26 weeks after transplantation, when immune suppression levels are reduced. The primary end point of this study is safety by assessing biopsy proven acute rejection (BPAR)/graft loss after MSC treatment. Secondary end points, all measured before and after MSC infusions, include: comparison of fibrosis in renal biopsy by quantitative Sirius Red scoring; de novo HLA antibody development and extensive immune monitoring; renal function measured by cGFR and iohexol clearance; CMV and BK infection and other opportunistic infections.DiscussionThis study will provide information on the safety of allogeneic MSC infusion and its effect on the incidence of BPAR/graft loss.Trial registration: NCT02387151

Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation

“…When injected in a protein-free buffer, MAPA-encapsulated mMSC half-life was unaffected by complement deactivation or macrophage reduction, suggesting that other mechanisms are responsible for their clearance. An adaptive immune response was elicited by injecting allogeneic hosts with mMSCs, which is consistent with prior results indicating that, despite expressing low levels of MHC molecules, MSCs still generate alloimmunization in both mice and humans (35,36). The ability of MAPA encapsulation to partially protect alloimmunized MSCs may be useful in therapies utilizing repeated dosages of allogeneic MSCs.…”

Efficacy and Safety of Autologous Bone Marrow Mesenchymal Stem Cell Transplantation in Patients with Diabetic Retinopathy

“…All patients received one intravenous (dorsal hand vein) infusion of ABMSCs, of which the total number for each patient was 3 × 10 6 /kg [22][23][24][25], sequentially infused within 30 min. Before transplantation, close monitoring of vital signs was performed including measurements of body temperature, blood glucose, blood pressure, pulse, blood oxygen saturation, and an electrocardiogram.…”

Mesenchymal Stem Cell‐Based Therapy for Kidney Disease: A Review of Clinical Evidence

“…This study will assert whether bmMSC can be used for tacrolimus withdrawal and whether this strategy leads to preservation of renal structure and function in renal recipients. In a third study, Reinders et al will assess the safety and feasibility of using allogenic bmMSC in 10 renal transplant recipients ( NCT02387151 ) [ 132 ]. Indeed, allogenic bmMSC offer the advantage of immediate availability for clinical use.…”