Dental Pulp Stem Cell-Derived Factors Alleviate Subarachnoid Hemorrhage-Induced Neuroinflammation and Ischemic Neurological Deficits.
Aneurysmal subarachnoid hemorrhage (aSAH), characterized by the extravasation of blood into the subarachnoid space caused by an intracranial aneurysm rupture, may lead to neurocognitive impairments and permanent disability and usually carries poor outcome. Dental or gingiva-derived stem cells have been shown to contribute to immune modulation and neuroregeneration, but the underlying mechanisms are unclear. In the present study, we sought to investigate whether dental pulp stem cells (DPSCs) secrete certain factor(s) that can ameliorate the neural damage and other manifestations in a rat aSAH model. Twenty-four hours after the induction of aSAH, microthrombosis, cortical vasoconstriction, and the decrease in microcirculation and tissue oxygen pressure were detected. Intrathecal administration of DPSC-derived conditioned media (DPSC-CM) ameliorated aSAH-induced vasoconstriction, neuroinflammation, and improved the oxygenation in the injured brain. Rotarod test revealed that the aSAH-induced cognitive and motor impairments were significantly improved by this DPSC-CM administration. Cytokine array indicated the major constituent of DPSC-CM was predominantly insulin growth factor-1 (IGF-1). Immunohistochemistry staining of injured brain tissue revealed the robust increase in Iba1-positive cells that were also ameliorated by DPSC-CM administration. Antibody-mediated neutralization of IGF-1 moderately deteriorated the rescuing effect of DPSC-CM on microcirculation, Iba1-positive cells in the injured brain area, and the cognitive/motor impairments. Taken together, the DPSC-derived secretory factors showed prominent therapeutic potential for aSAH. This therapeutic efficacy may include improvement of microcirculation, alleviation of neuroinflammation, and microglial activation; partially through IGF-1-dependent mechanisms.
['Chen|Te-Fu|TF|', 'Chen|Kuo-We|KW|', 'Chien|Yueh|Y|', 'Lai|Ying-Hsiu|YH|', 'Hsieh|Sung-Tsang|ST|', 'Ma|Hsin-Yi|HY|', 'Wang|Kou-Chung|KC|0000-0002-4083-4689', 'Shiau|Chia-Yang|CY|']
D000818:Animals D002545:Brain Ischemia D002135:Calcium-Binding Proteins D017077:Culture Media, Conditioned D003782:Dental Pulp D004195:Disease Models, Animal D015870:Gene Expression D007278:Injections, Spinal D007334:Insulin-Like Growth Factor I D008297:Male D008833:Microcirculation D008840:Microfilament Proteins D019965:Neurocognitive Disorders D018696:Neuroprotective Agents D010101:Oxygen Consumption D011596:Psychomotor Disorders D051381:Rats D017208:Rats, Wistar D045442:Rotarod Performance Test D013234:Stem Cells D013345:Subarachnoid Hemorrhage D013927:Thrombosis D014661:Vasoconstriction
neuroinflammation aneurysmal subarachnoid hemorrhage stem cell conditioned medium