Transplantation of human dental pulp stem cells ameliorates brain damage following acute cerebral ischemia

• Published in: Biomedicine & pharmacotherapy Vol. 108; pp. 1005 - 1014
• Main Authors: Nito, Chikako, Sowa, Kota, Nakajima, Masataka, Sakamoto, Yuki, Suda, Satoshi, Nishiyama, Yasuhiro, Nakamura-Takahashi, Aki, Nitahara-Kasahara, Yuko, Ueda, Masayuki, Okada, Takashi, Kimura, Kazumi
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.12.2018
• Subjects: Animals; Brain - cytology; Brain Ischemia - pathology; Dental Pulp - cytology; Dental pulp stem cells; Focal cerebral ischemia; Humans; Infarction, Middle Cerebral Artery - pathology; Inflammation; Male; Neuroprotection; Rats; Rats, Sprague-Dawley; Recovery of Function - physiology; Reperfusion - methods; Stem Cells - cytology; Transplantation; Transplantation - methods; Focal cerebral ischemia; Neuroprotection; Transplantation; Inflammation; Dental pulp stem cells
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.09.084

Numerous experimental studies have shown that cellular therapy, including human dental pulp stem cells (DPSCs), is an attractive strategy for ischemic brain injury. Herein, we examined the effects of intravenous DPSC administration after transient middle cerebral artery occlusion in rats. Male Sprague-Dawley rats received a transient 90 min middle cerebral artery occlusion. DPSCs (1 × 106 cells) or vehicle were administered via the femoral vein at 0 h or 3 h after ischemia-reperfusion. PKH26, a red fluorescent cell linker, was used to track the transplanted cells in the brain. Infarct volume, neurological deficits, and immunological analyses were performed at 24 h and 72 h after reperfusion. PKH26-positive cells were observed more frequently in the ipsilateral than the contralateral hemisphere. DPSCs transplanted at 0 h after reperfusion significantly reduced infarct volume and reversed motor deficits at 24 h and 72 h recovery. DPSCs transplanted at 3 h after reperfusion also significantly reduced infarct volume and improved motor function compared with vehicle groups at 24 h and 72 h recovery. Further, DPSC transplantation significantly inhibited microglial activation and pro-inflammatory cytokine expression compared with controls at 72 h after reperfusion. Moreover, DPSCs attenuated neuronal degeneration in the cortical ischemic boundary area. Systemic delivery of human DPSCs after reperfusion reduced ischemic damage and improved functional recovery in a rodent ischemia model, with a clinically relevant therapeutic window. The neuroprotective action of DPSCs may relate to the modulation of neuroinflammation during the acute phase of stroke.