Mannitol-enhanced delivery of stem cells and their growth factors across the blood-brain barrier.
Ischemic brain injury in adults and neonates is a significant clinical problem with limited therapeutic interventions. Currently, clinicians have only tPA available for stroke treatment and hypothermia for cerebral palsy. Owing to the lack of treatment options, there is a need for novel treatments such as stem cell therapy. Various stem cells including cells from embryo, fetus, perinatal, and adult tissues have proved effective in preclinical and small clinical trials. However, a limiting factor in the success of these treatments is the delivery of the cells and their by-products (neurotrophic factors) into the injured brain. We have demonstrated that mannitol, a drug with the potential to transiently open the blood-brain barrier and facilitate the entry of stem cells and trophic factors, as a solution to the delivery problem. The combination of stem cell therapy and mannitol may improve therapeutic outcomes in adult stroke and neonatal cerebral palsy.
Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
Gabriel S
GS
Gonzales-Portillo
Paul R
PR
Sanberg
Max
M
Franzblau
Chiara
C
Gonzales-Portillo
Theo
T
Diamandis
Meaghan
M
Staples
Cyndy D
CD
Sanberg
Cesar V
CV
Borlongan
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D036101:Cord Blood Stem Cell Transplantation; D006801:Humans; D007511:Ischemia / Q000628:therapy; D008353:Mannitol / Q000737:chemistry* / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology*; D020521:Stroke / Q000628:therapy
D009414:Nerve Growth Factors; D008353:Mannitol