Human adult dental pulp stem cells enhance poststroke functional recovery through non-neural replacement mechanisms

Wai Khay Leong, Tanya Henshall, Agnes Arthur, Karlea Kremer, Martin Lewis, Stephen Helps, John Field, M Hamilton-Bruce, Scott Warming, Jim Manavis, Robert Vink, S Gronthos, Simon Koblar

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    84 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)177-187
    Number of pages11
    JournalStem Cells Translational Medicine
    Volume1
    Issue number3
    DOIs
    Publication statusPublished - 2012

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    Leong, W. K., Henshall, T., Arthur, A., Kremer, K., Lewis, M., Helps, S., Field, J., Hamilton-Bruce, M., Warming, S., Manavis, J., Vink, R., Gronthos, S., & Koblar, S. (2012). Human adult dental pulp stem cells enhance poststroke functional recovery through non-neural replacement mechanisms. Stem Cells Translational Medicine, 1(3), 177-187. https://doi.org/10.5966/sctm.2011-0039