title: Theranostic effect of serial manganese-enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma.
abstract: Although human embryonic stem cell (hESC) hold therapeutic potential, teratoma formation has deterred clinical translation. Manganese (Mn(2+)) enters metabolically active cells through voltage-gated calcium channels and subsequently, induces T(1) shortening. We hypothesized that serial manganese-enhanced MRI would have theranostic effect to assess hESC survival, teratoma formation, and hESC-derived teratoma reduction through intracellular accumulation of Mn(2+). Firefly luciferase transduced hESCs (hESC-Lucs) were transplanted into severe combined immunodeficient mouse hindlimbs to form teratoma. The chemotherapy group was injected with MnCl(2) intraperitoneally three times a week. The control group was given MnCl(2) only prior to manganese-enhanced MRI. Longitudinal evaluation by manganese-enhanced MRI and bioluminescence imaging was performed. The chemotherapy group showed significant reduction in the teratoma volume and luciferase activity at weeks 6 and 8. Histology revealed increased proportion of dead cells and caspase 3 positive cells in the chemotherapy group. Systemic administration of MnCl(2) enabled simultaneous monitoring and elimination of hESC-derived teratoma cells by higher intracellular accumulation of Mn(2+).
authors.affiliation: Department of Medicine, Stanford University, Stanford, California, United States of America.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Chung
authors.forename: Rajesh
authors.initials: R
authors.lastname: Dash
authors.forename: Kehkooi
authors.initials: K
authors.lastname: Kee
authors.forename: Joëlle K
authors.initials: JK
authors.lastname: Barral
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kosuge
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robbins
authors.forename: Dwight
authors.initials: D
authors.lastname: Nishimura
authors.forename: Renee A
authors.initials: RA
authors.lastname: Reijo-Pera
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002712:Chlorides / Q000627:therapeutic use*; D003287:Contrast Media / Q000627:therapeutic use; D053595:Embryonic Stem Cells / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D017895:Manganese Compounds / Q000627:therapeutic use*; D051379:Mice; D013724:Teratoma / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; C025340:manganese chloride