Immunosuppression does not affect human bone marrow mesenchymal stromal cell efficacy after transplantation in traumatized mice brain.
The need for immunosuppression after allo/xenogenic mesenchymal stromal cell (MSC) transplantation is debated. This study compared the long-term effects of human (h) bone marrow MSC transplant in immunocompetent or immunosuppressed traumatic brain injured (TBI) mice. C57Bl/6 male mice were subjected to TBI or sham surgery followed 24 h later by an intracerebroventricular infusion of phosphate buffer saline (PBS, control) or hMSC (150,000/5 μl). Immunocompetent and cyclosporin A immunosuppressed (CsA) mice were analyzed for gene expression at 72 h, functional deficits and histological analysis at five weeks. Gene expression analysis showed the effectiveness of immunosuppression (INFγ reduction in CsA treated groups), with no evidence of early rejection (no changes of MHCII and CD86 in all TBI groups) and selective induction of T-reg (increase of Foxp3) only in the TBI hMSC group. Five weeks after TBI, hMSC had comparable efficacy, with functional recovery (on both sensorimotor and cognitive deficits) and structural protection (contusion volume, vessel rescue effect, gliotic scar reduction, induction of neurogenesis) in immunosuppressed and immunocompetent mice. Therefore, long-term hMSC efficacy in TBI is not dependent on immunosuppressive treatment. These findings could have important clinical implication since immunosuppression in acute TBI patients may increase their risk of infection and not be tolerated.
IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Department of Neuroscience, Milan, Italy.
Francesca
F
Pischiutta
Centro Ricerca Tettamanti, Clinica Pediatrica, Università Milano-Bicocca, Ospedale San Gerardo/Fondazione MBBM, Monza, Italy.
Giovanna
G
D'Amico
Centro Ricerca Tettamanti, Clinica Pediatrica, Università Milano-Bicocca, Ospedale San Gerardo/Fondazione MBBM, Monza, Italy.
Erica
E
Dander
Centro Ricerca Tettamanti, Clinica Pediatrica, Università Milano-Bicocca, Ospedale San Gerardo/Fondazione MBBM, Monza, Italy.
Andrea
A
Biondi
Laboratory for Cell Therapy "Stefano Verri", Paediatric Department, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
Ettore
E
Biagi
Neuroanesthesia and Neurointensive Care Unit, Department of Perioperative Medicine and Intensive Care, San Gerardo Hospital, Monza, Italy.
Giuseppe
G
Citerio
IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Department of Neuroscience, Milan, Italy. Electronic address: desimoni@marionegri.it.
Maria Grazia
MG
De Simoni
IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Department of Neuroscience, Milan, Italy.
Elisa R
ER
Zanier
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D016572:Cyclosporine / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006084:Graft Rejection / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009483:Neuropsychological Tests; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine
Brain protection; Cyclosporin A; Immunosuppression; Mesenchymal stromal cells; Stem cell transplantation; Traumatic brain injury