TY - JOUR
T1 - Safety of allogeneic bone marrow derived mesenchymal stromal cell therapy in renal transplant recipients
T2 - The neptune study
AU - Reinders, Marlies E.J.
AU - Dreyer, Geertje J.
AU - Bank, Jonna R.
AU - Roelofs, Helene
AU - Heidt, Sebastiaan
AU - Roelen, Dave L.
AU - Zandvliet, Maarten L.
AU - Huurman, Volkert A.L.
AU - Fibbe, Wim E.
AU - Kooten, Cees
AU - Claas, Frans H.J.
AU - Rabelink, Ton J.
AU - de Fijter, Johan W.
N1 - Publisher Copyright:
© 2015 Reinders et al.
PY - 2015/11/4
Y1 - 2015/11/4
N2 - Background: Mesenchymal 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/design: 10 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. Discussion: This study will provide information on the safety of allogeneic MSC infusion and its effect on the incidence of BPAR/graft loss.
AB - Background: Mesenchymal 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/design: 10 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. Discussion: This study will provide information on the safety of allogeneic MSC infusion and its effect on the incidence of BPAR/graft loss.
UR - http://www.scopus.com/inward/record.url?scp=84946416706&partnerID=8YFLogxK
U2 - 10.1186/s12967-015-0700-0
DO - 10.1186/s12967-015-0700-0
M3 - Article
C2 - 26537851
AN - SCOPUS:84946416706
SN - 1479-5876
VL - 13
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
IS - 1
M1 - 344
ER -