BACKGROUND AND OBJECTIVES: Mesenchymal stromal cells (MSCs) abrogate alloimmune response in vitro, suggesting a novel cell-based approach in transplantation. Moving this concept toward clinical application in organ transplantation should be critically assessed. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: A safety and clinical feasibility study (ClinicalTrials.gov, NCT00752479) of autologous MSC infusion was conducted in two recipients of kidneys from living-related donors. Patients were given T cell-depleting induction therapy and maintenance immunosuppression with cyclosporine and mycophenolate mofetil. On day 7 posttransplant, MSCs were administered intravenously. Clinical and immunomonitoring of MSC-treated patients was performed up to day 360 postsurgery. RESULTS: Serum creatinine levels increased 7 to 14 days after cell infusion in both MSC-treated patients. A graft biopsy in patient 2 excluded acute graft rejection, but showed a focal inflammatory infiltrate, mostly granulocytes. In patient 1 protocol biopsy at 1-year posttransplant showed a normal graft. Both MSC-treated patients are in good health with stable graft function. A progressive increase of the percentage of CD4+CD25highFoxP3+CD127- Treg and a marked inhibition of memory CD45RO+RA-CD8+ T cell expansion were observed posttransplant. Patient T cells showed a profound reduction of CD8+ T cell activity. CONCLUSIONS: Findings from this study in the two patients show that MSC infusion in kidney transplant recipients is feasible, allows enlargement of Treg in the peripheral blood, and controls memory CD8+ T cell function. Future clinical trials with MSCs to look with the greatest care for unwanted side effects is advised.
BACKGROUND AND OBJECTIVES: Mesenchymal stromal cells (MSCs) abrogate alloimmune response in vitro, suggesting a novel cell-based approach in transplantation. Moving this concept toward clinical application in organ transplantation should be critically assessed. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: A safety and clinical feasibility study (ClinicalTrials.gov, NCT00752479) of autologous MSC infusion was conducted in two recipients of kidneys from living-related donors. Patients were given T cell-depleting induction therapy and maintenance immunosuppression with cyclosporine and mycophenolate mofetil. On day 7 posttransplant, MSCs were administered intravenously. Clinical and immunomonitoring of MSC-treated patients was performed up to day 360 postsurgery. RESULTS: Serum creatinine levels increased 7 to 14 days after cell infusion in both MSC-treated patients. A graft biopsy in patient 2 excluded acute graft rejection, but showed a focal inflammatory infiltrate, mostly granulocytes. In patient 1 protocol biopsy at 1-year posttransplant showed a normal graft. Both MSC-treated patients are in good health with stable graft function. A progressive increase of the percentage of CD4+CD25highFoxP3+CD127- Treg and a marked inhibition of memory CD45RO+RA-CD8+ T cell expansion were observed posttransplant. Patient T cells showed a profound reduction of CD8+ T cell activity. CONCLUSIONS: Findings from this study in the two patients show that MSC infusion in kidney transplant recipients is feasible, allows enlargement of Treg in the peripheral blood, and controls memory CD8+ T cell function. Future clinical trials with MSCs to look with the greatest care for unwanted side effects is advised.
Authors: Varsha D K D Sewgobind; Marcia M L Kho; Luc J W van der Laan; Thijs K Hendrikx; Thea van Dam; Hugo W Tilanus; Jan N M IJzermans; Willem Weimar; Carla C Baan Journal: Nephrol Dial Transplant Date: 2009-01-28 Impact factor: 5.992
Authors: F C Popp; E Eggenhofer; P Renner; P Slowik; S A Lang; H Kaspar; E K Geissler; P Piso; H J Schlitt; M H Dahlke Journal: Transpl Immunol Date: 2008-08-30 Impact factor: 1.708
Authors: Helen Karlsson; Sujith Samarasinghe; Lynne M Ball; Berit Sundberg; Arjan C Lankester; Francesco Dazzi; Mehmet Uzunel; Kanchan Rao; Paul Veys; Katarina Le Blanc; Olle Ringdén; Persis J Amrolia Journal: Blood Date: 2008-04-28 Impact factor: 22.113
Authors: A U Engela; C C Baan; N H R Litjens; M Franquesa; M G H Betjes; W Weimar; M J Hoogduijn Journal: Clin Exp Immunol Date: 2013-12 Impact factor: 4.330
Authors: Xiang-Yang Zhu; Victor Urbieta-Caceres; James D Krier; Stephen C Textor; Amir Lerman; Lilach O Lerman Journal: Stem Cells Date: 2013-01 Impact factor: 6.277