Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial.

INTRODUCTION: Regenerative medicine and cell therapies have been gaining much attention among clinicians. Therapeutic infusion of mesenchymal stromal cells (MSCs) is now a leading investigational strategy for the treatment of acute graft-versus-host disease (aGVHD). Bone marrow MSCs are approved for manufacture and marketing as a cell therapy for aGVHD. Our non-clinical studies confirmed that human amnion-derived MSCs had immunomodulatory activity equal to or higher than that of human bone marrow MSCs. This study will aim to evaluate the safety and efficacy of amnion-derived MSCs (AM01) in patients with steroid-refractory aGVHD. METHODS AND ANALYSIS: This study will be a multicentre, single-arm, open-label trial (an interventional study). This clinical trial will begin with a low-dose group, and when safety has been confirmed in at least three cases in the low-dose group, treatment will begin for the high-dose group, for which the safety will also be verified. The primary endpoint is to assess the safety of intravenous infusion therapy of AM01 within 24 hours after intravenous infusion of AM01. The secondary endpoint is to explore the efficacy of intravenous infusion therapy with AM01. ETHICS AND DISSEMINATION: The institutional review boards of all participating hospitals approved this study protocol (latest V3.3.0, 3 August 2018). Final data will be publicly announced. A report releasing the study results will be submitted for publication to an appropriate peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000029945.

Age-related changes in gingival blood flow parameters measured using laser speckle flowmetry.

Previous studies have suggested a possible relationship between age-related changes to human gingival hemodynamics and periodontal disease. However, firmly establishing this has been difficult because of a lack of suitable tools. Our study investigated whether a non-invasive laser speckle flowgraphy (LSFG)-based 2-dimensional technique could be used to assess maxillary anterior gingival blood flow under resting conditions. In total, 124 healthy male volunteers aged between 22 and 69 years were included in the study and delineated into young (Y; 22-37 years, n = 45), middle-aged (M; 38-53 years, n = 43), and elderly groups (E; 54-69 years, n = 36). The differences in gingival hemodynamics were compared among age groups and pulse waveform analysis performed to calculate blood flow indices, mean blur rate (MBR), gingival vascular conductance (MBR/mean blood pressure [MBP]), and three pulse waveform parameters (acceleration time index [ATI], falling rate, and blowout time [BOT]). Although no statistically significant differences were observed in the MBR of the three age groups, vascular conductance (MBR/MBP) was lower in groups M and E compared to group Y and correlated negatively with age. ATI and falling rates were also significantly higher in group E relative to group Y, whereas average BOT was significantly lower. All of the assessed parameters correlated with age. These data suggest that there are age-related decreases in the ability to maintain blood flow in the human maxillary anterior gingiva under resting conditions which may impact the likelihood of periodontal disease.