title: Tracking and Therapeutic Value of Human Adipose Tissue-derived Mesenchymal Stem Cell Transplantation in Reducing Venous Neointimal Hyperplasia Associated with Arteriovenous Fistula.
abstract: OBJECTIVE
  To determine if adventitial transplantation of human adipose tissue-derived mesenchymal stem cells (MSCs) to the outflow vein of B6.Cg-Foxn1(nu)/J mice with arteriovenous fistula (AVF) at the time of creation would reduce monocyte chemoattractant protein-1 (Mcp-1) gene expression and venous neointimal hyperplasia. The second aim was to track transplanted zirconium 89 ((89)Zr)-labeled MSCs serially with positron emission tomography (PET) for 21 days.
  
  
  METHODS
  All animal experiments were performed according to protocols approved by the institutional animal care and use committee. Fifty B6.Cg-Foxn1(nu)/J mice were used to accomplish the study aims. Green fluorescent protein was used to stably label 2.5 × 10(5) MSCs, which were injected into the adventitia of the outflow vein at the time of AVF creation in the MSC group. Eleven mice died after AVF placement. Animals were sacrificed on day 7 after AVF placement for real-time polymerase chain reaction (n = 6 for MSC and control groups) and histomorphometric (n = 6 for MSC and control groups) analyses and on day 21 for histomorphometric analysis only (n = 6 for MSC and control groups). In a separate group of experiments (n = 3), animals with transplanted (89)Zr-labeled MSCs were serially imaged with PET for 3 weeks. Multiple comparisons were performed with two-way analysis of variance, followed by the Student t test with post hoc Bonferroni correction.
  
  
  RESULTS
  In vessels with transplanted MSCs compared with control vessels, there was a significant decrease in Mcp-1 gene expression (day 7: mean reduction, 62%; P = .029), with a significant increase in the mean lumen vessel area (day 7: mean increase, 176% [P = .013]; day 21: mean increase, 415% [P = .011]). Moreover, this was accompanied by a significant decrease in Ki-67 index (proliferation on day 7: mean reduction, 81% [P = .0003]; proliferation on day 21: mean reduction, 60%, [P = .016]). Prolonged retention of MSCs at the adventitia was evidenced by serial PET images of (89)Zr-labeled cells.
  
  
  CONCLUSIONS
  Adventitial transplantation of MSCs decreases Mcp-1 gene expression, accompanied by a reduction in venous neointimal hyperplasia.
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Binxia
authors.initials: B
authors.lastname: Yang
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Akshaar
authors.initials: A
authors.lastname: Brahmbhatt
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Nieves Torres
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Brian
authors.initials: B
authors.lastname: Thielen
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: McCall
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Sean
authors.initials: S
authors.lastname: Engel
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Aditya
authors.initials: A
authors.lastname: Bansal
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Pandey
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Allan B
authors.initials: AB
authors.lastname: Dietz
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Leof
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: DeGrado
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Mukhopadhyay
authors.affiliation: From the Vascular and Interventional Radiology Translational Laboratory, Department of Radiology (B.Y., A. Brahmbhatt, E.N.T., B.T., D.L.M., S.E., A. Bansal, M.K.P., T.R.D., S.M.), and Department of Biochemistry and Molecular Biology (A.B.D., E.B.L., D.M., S.M.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Misra
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D006801:Humans; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D020287:In Situ Nick-End Labeling; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D058426:Neointima / Q000473:pathology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D019275:Radiopharmaceuticals