title: A theranostic small interfering RNA nanoprobe protects pancreatic islet grafts from adoptively transferred immune rejection.
abstract: Islet transplantation has recently emerged as an acceptable clinical modality for restoring normoglycemia in patients with type 1 diabetes mellitus (T1DM). The long-term survival and function of islet grafts is compromised by immune rejection-related factors. Downregulation of factors that mediate immune rejection using RNA interference holds promise for improving islet graft resistance to damaging factors after transplantation. Here, we used a dual-purpose therapy/imaging small interfering (si)RNA magnetic nanoparticle (MN) probe that targets β(2) microglobulin (B2M), a key component of the major histocompatibility class I complex (MHC I). In addition to serving as a siRNA carrier, this MN-siB2M probe enables monitoring of graft persistence noninvasively using magnetic resonance imaging (MRI). Human islets labeled with these MNs before transplantation into B2M (null) NOD/scid mice showed significantly improved preservation of graft volume starting at 2 weeks, as determined by longitudinal MRI in an adoptive transfer model (P < 0.05). Furthermore, animals transplanted with MN-siB2M-labeled islets demonstrated a significant delay of up to 23.8 ± 4.8 days in diabetes onset after the adoptive transfer of T cells relative to 6.5 ± 4.5 days in controls. This study demonstrated that our approach could protect pancreatic islet grafts from immune rejection and could potentially be applied to allotransplantation and prevention of the autoimmune recurrence of T1DM in islet transplantation or endogenous islets.
authors.affiliation: Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Mehmet V
authors.initials: MV
authors.lastname: Yigit
authors.forename: Chongzhao
authors.initials: C
authors.lastname: Ran
authors.forename: Alana
authors.initials: A
authors.lastname: Ross
authors.forename: Lingling
authors.initials: L
authors.lastname: Wei
authors.forename: Guangping
authors.initials: G
authors.lastname: Dai
authors.forename: Zdravka
authors.initials: Z
authors.lastname: Medarova
authors.forename: Anna
authors.initials: A
authors.lastname: Moore
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods*; D008285:Major Histocompatibility Complex / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering