Construction and Evaluation of a Subcutaneous Splenic Injection Port for Serial Intraportal Vein Cell Delivery in Murine Disease Models

The liver is the largest internal organ and the center of homeostatic metabolism. Liver-directed cell transplantation is, therefore, an attractive therapeutic option to treat various metabolic disorders as well as liver diseases. Although clinical liver-directed cell transplantation requires multipl...

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Main Authors: Toshio Miki, Chika Takano, Irving M. Garcia, Brendan H. Grubbs
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/5419501
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author Toshio Miki
Chika Takano
Irving M. Garcia
Brendan H. Grubbs
author_facet Toshio Miki
Chika Takano
Irving M. Garcia
Brendan H. Grubbs
author_sort Toshio Miki
collection DOAJ
description The liver is the largest internal organ and the center of homeostatic metabolism. Liver-directed cell transplantation is, therefore, an attractive therapeutic option to treat various metabolic disorders as well as liver diseases. Although clinical liver-directed cell transplantation requires multiple cell injections into the portal venous system, a mouse model is lacking which allows us to perform repetitive cell injections into the portal venous system. Here, we propose a surgical model that utilizes the spleen as a subcutaneous injection port. Mouse spleens were translocated under the skin with intact vascular pedicles. Human placental stem cell transplantations were performed one week following this port construction and repeated three times. Cell distribution was analyzed by quantifying human DNA using human Alu-specific primers. About 50% of the transplanted cells were located homogeneously in the liver one hour after the splenic port injection. Fluorescent-labeled cell tracking and antihuman mitochondrion immunohistochemistry studies demonstrated that the cells localized predominantly in small distal portal branches. A similar cell distribution was observed after multiple cell injections. These data confirm that the subcutaneous splenic injection port is suitable for performing repetitive cell transplantation into the portal venous system of mouse models.
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spelling doaj-art-980ec754a65b4862aba50600f1e378922025-02-03T01:11:35ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/54195015419501Construction and Evaluation of a Subcutaneous Splenic Injection Port for Serial Intraportal Vein Cell Delivery in Murine Disease ModelsToshio Miki0Chika Takano1Irving M. Garcia2Brendan H. Grubbs3Department of Surgery, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 509A, Los Angeles, CA 90033-9141, USADepartment of Surgery, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 509A, Los Angeles, CA 90033-9141, USADepartment of Surgery, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 509A, Los Angeles, CA 90033-9141, USADepartment of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, 1200 N. State Street, IRD 220, Los Angeles, CA 90033, USAThe liver is the largest internal organ and the center of homeostatic metabolism. Liver-directed cell transplantation is, therefore, an attractive therapeutic option to treat various metabolic disorders as well as liver diseases. Although clinical liver-directed cell transplantation requires multiple cell injections into the portal venous system, a mouse model is lacking which allows us to perform repetitive cell injections into the portal venous system. Here, we propose a surgical model that utilizes the spleen as a subcutaneous injection port. Mouse spleens were translocated under the skin with intact vascular pedicles. Human placental stem cell transplantations were performed one week following this port construction and repeated three times. Cell distribution was analyzed by quantifying human DNA using human Alu-specific primers. About 50% of the transplanted cells were located homogeneously in the liver one hour after the splenic port injection. Fluorescent-labeled cell tracking and antihuman mitochondrion immunohistochemistry studies demonstrated that the cells localized predominantly in small distal portal branches. A similar cell distribution was observed after multiple cell injections. These data confirm that the subcutaneous splenic injection port is suitable for performing repetitive cell transplantation into the portal venous system of mouse models.http://dx.doi.org/10.1155/2019/5419501
spellingShingle Toshio Miki
Chika Takano
Irving M. Garcia
Brendan H. Grubbs
Construction and Evaluation of a Subcutaneous Splenic Injection Port for Serial Intraportal Vein Cell Delivery in Murine Disease Models
Stem Cells International
title Construction and Evaluation of a Subcutaneous Splenic Injection Port for Serial Intraportal Vein Cell Delivery in Murine Disease Models
title_full Construction and Evaluation of a Subcutaneous Splenic Injection Port for Serial Intraportal Vein Cell Delivery in Murine Disease Models
title_fullStr Construction and Evaluation of a Subcutaneous Splenic Injection Port for Serial Intraportal Vein Cell Delivery in Murine Disease Models
title_full_unstemmed Construction and Evaluation of a Subcutaneous Splenic Injection Port for Serial Intraportal Vein Cell Delivery in Murine Disease Models
title_short Construction and Evaluation of a Subcutaneous Splenic Injection Port for Serial Intraportal Vein Cell Delivery in Murine Disease Models
title_sort construction and evaluation of a subcutaneous splenic injection port for serial intraportal vein cell delivery in murine disease models
url http://dx.doi.org/10.1155/2019/5419501
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AT irvingmgarcia constructionandevaluationofasubcutaneoussplenicinjectionportforserialintraportalveincelldeliveryinmurinediseasemodels
AT brendanhgrubbs constructionandevaluationofasubcutaneoussplenicinjectionportforserialintraportalveincelldeliveryinmurinediseasemodels