TY - JOUR
T1 - Human adult dental pulp stem cells enhance poststroke functional recovery through non-neural replacement mechanisms
AU - Leong, Wai Khay
AU - Henshall, Tanya
AU - Arthur, Agnes
AU - Kremer, Karlea
AU - Lewis, Martin
AU - Helps, Stephen
AU - Field, John
AU - Hamilton-Bruce, M
AU - Warming, Scott
AU - Manavis, Jim
AU - Vink, Robert
AU - Gronthos, S
AU - Koblar, Simon
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Dental pulp stem cells
KW - Functional recovery
KW - Rat model
KW - Stem cell transplantation
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=84872101947&partnerID=8YFLogxK
U2 - 10.5966/sctm.2011-0039
DO - 10.5966/sctm.2011-0039
M3 - Article
SN - 2157-6564
VL - 1
SP - 177
EP - 187
JO - Stem Cells Translational Medicine
JF - Stem Cells Translational Medicine
IS - 3
ER -