Nasal administration of stem cells: a promising novel route to treat neonatal ischemic brain damage.
Mesenchymal stem cell (MSC) transplantation is a promising therapy to regenerate the brain after an ischemic event. We investigated the possibility to use the nasal route as a noninvasive method to repair the neonatal damaged brain. Nine-day-old mice underwent cerebral hypoxia-ischemia (HI), and MSCs were transplanted intranasally 10 d after HI. At 28 d after HI, MSCs were still present in the affected hemisphere but had not differentiated into cerebral cell types. Intranasal MSC treatment significantly improved sensorimotor function in the cylinder rearing test at 21 and 28 d after HI. Furthermore, intranasal MSC treatment decreased gray and white matter area loss when determined 28 d after HI by 34 and 37%, respectively. MSC cultured in vitro with brain extracts obtained 10 d after HI, responded to the ischemic brain by up-regulation of several growth factors, including fibroblast growth factor 2 and nerve growth factor in comparison with brain extracts of sham-operated controls. In conclusion, MSC can reliably be delivered to the brain via the nasal route to induce functional recovery and a reduction in brain lesion size. We propose that MSC function by stimulating endogenous cerebral repair by adapting their secretion profile to the ischemic brain leading to up-regulation of repair promoting factors.
van Velthoven
Cindy T J
CT
Laboratory for Neuroimmunology and Developmental Origins of Disease, Department of Neonatology, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands.
Kavelaars
Annemieke
A
van Bel
Frank
F
Heijnen
Cobi J
CJ
D000281:Administration, Intranasal; D000818:Animals; D001522:Behavior, Animal; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D020869:Gene Expression Profiling; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000628:therapy; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009483:Neuropsychological Tests; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D016896:Treatment Outcome