title: Human adult dental pulp stem cells enhance poststroke functional recovery through non-neural replacement mechanisms.
abstract: Human adult dental pulp stem cells (DPSCs), derived from third molar teeth, are multipotent and have the capacity to differentiate into neurons under inductive conditions both in vitro and following transplantation into the avian embryo. In this study, we demonstrate that the intracerebral transplantation of human DPSCs 24 hours following focal cerebral ischemia in a rodent model resulted in significant improvement in forelimb sensorimotor function at 4 weeks post-treatment. At this time, 2.3 ± 0.7% of engrafted cells had survived in the poststroke brain and demonstrated targeted migration toward the stroke lesion. In the peri-infarct striatum, transplanted DPSCs differentiated into astrocytes in preference to neurons. Our data suggest that the dominant mechanism of action underlying DPSC treatment that resulted in enhanced functional recovery is unlikely to be due to neural replacement. Functional improvement is more likely to be mediated through DPSC-dependent paracrine effects. This study provides preclinical evidence for the future use of human DPSCs in cell therapy to improve outcome in stroke patients.
authors.affiliation: Centre for Stem Cell Research, Robinson Institute, University of Adelaide, South Australia, Australia.
authors.forename: Wai Khay
authors.initials: WK
authors.lastname: Leong
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Henshall
authors.forename: Agnes
authors.initials: A
authors.lastname: Arthur
authors.forename: Karlea L
authors.initials: KL
authors.lastname: Kremer
authors.forename: Martin D
authors.initials: MD
authors.lastname: Lewis
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Helps
authors.forename: John
authors.initials: J
authors.lastname: Field
authors.forename: Monica A
authors.initials: MA
authors.lastname: Hamilton-Bruce
authors.forename: Scott
authors.initials: S
authors.lastname: Warming
authors.forename: Jim
authors.initials: J
authors.lastname: Manavis
authors.forename: Robert
authors.initials: R
authors.lastname: Vink
authors.forename: Stan
authors.initials: S
authors.lastname: Gronthos
authors.forename: Simon A
authors.initials: SA
authors.lastname: Koblar
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000502:physiology; D001522:Behavior, Animal; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation; D003782:Dental Pulp / Q000166:cytology* / Q000502:physiology; D005552:Forelimb / Q000166:cytology / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009483:Neuropsychological Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D055139:Sensory Gating; D033581:Stem Cell Transplantation; D020521:Stroke / Q000517:prevention & control*