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

Abstract

IntroductionRegenerative 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 analysisThis 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 disseminationThe 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 numberUMIN000029945.

Advantage of fat-derived CD73 positive cells from multiple human tissues, prospective isolated mesenchymal stromal cells

“…These results suggest tissue-specific characteristics of CD73-positive MSCs, along with notable heterogeneity among individuals for enrichment in the subcutaneous www.nature.com/scientificreports/ fat and amnion. As clinical studies use MSCs derived from various tissues 10,11,15 , our results highlight the importance of considering the potential different characteristics of the cells depending on the source tissue, which could impact the therapeutic efficacy. CD73-positive cells exhibited CFU-F ability in varying degrees between donors as shown in supplemental Fig.…”

“…MSCs are characterized by the ability to form fibroblastic colonies, self-renew, and differentiate into several mesenchymal lineages 4 . Owing to their differentiation and immune regulation abilities, MSCs have been tested in approximately 1,000 clinical trials to date for the treatment of multiple conditions, including heart disease, neural diseases, graft-versus-host disease, and autoimmune rheumatic diseases 5 – 11 . The conventional method to isolate MSCs involves culture with plastic adherence over series of passages, which has been associated with several technical limitations, including high heterogeneity of adherent cells, altered morphological features, and cellular senescence, thereby limiting their clinical potential 12 .…”

Biomimetic cell-adhesive ligand-functionalized peptide composite hydrogels maintain stemness of human amniotic mesenchymal stem cells

“…Moreover, hAMSCs can be acquired non-invasively and do not involve medical ethical or legal problems, because amniotic membrane is a waste product of perinatal tissue sources, which is routinely discarded after delivery [ 20 , 31 ]. Therefore, hAMSCs have been successively serviced as a viable resource to treat diseases, such as neurological disorders [ 32 ], liver [ 33 ] and lung injury [ 34 ], chronic wound [ 35 ], and acute inflammatory diseases [ 36 ], and exhibit great potential in bone and osteochondral regeneration [ 31 , 37 ].…”

Human Amniotic Mesenchymal Stem Cells Inhibit aGVHD in Humanized NPG Mice by Regulating Balance of Treg Versus T Effector Cells

“…Thus, the active proliferative potential, low immunogenic pro le, anti-in ammatory function of hAMSCs can be bene cial to the therapy of in ammation-related diseases, and immunosuppression. Kenichi Yamahara et al [9] found that patients with steroid-refractory aGVHD infusion of hAMSCs is safety and e cacy. Our previously study demonstrated that hAMSCs can induce Th1cells into Th2 cells in vitro [10].…”