In utero transplantation of myoblasts and adipose-derived mesenchymal stem cells to murine models of Duchenne muscular dystrophy does not lead to engraftment and frequently results in fetal death

Introduction: Duchenne muscular dystrophy (DMD) is a progressive disease that leads to damage of muscle and myocardium due to genetic abnormalities in the dystrophin gene. In utero cell transplantation that might facilitate allogenic transplantation is worth considering to treat this disease. Method...

Full description

Bibliographic Details
Main Authors: Yuki Kihara, Yukie Tanaka, Masanari Ikeda, Jun Homma, Ryo Takagi, Keiko Ishigaki, Keitaro Yamanouchi, Hiroaki Honda, Satoru Nagata, Masayuki Yamato
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Regenerative Therapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352320422001006
_version_ 1811188686706966528
author Yuki Kihara
Yukie Tanaka
Masanari Ikeda
Jun Homma
Ryo Takagi
Keiko Ishigaki
Keitaro Yamanouchi
Hiroaki Honda
Satoru Nagata
Masayuki Yamato
author_facet Yuki Kihara
Yukie Tanaka
Masanari Ikeda
Jun Homma
Ryo Takagi
Keiko Ishigaki
Keitaro Yamanouchi
Hiroaki Honda
Satoru Nagata
Masayuki Yamato
author_sort Yuki Kihara
collection DOAJ
description Introduction: Duchenne muscular dystrophy (DMD) is a progressive disease that leads to damage of muscle and myocardium due to genetic abnormalities in the dystrophin gene. In utero cell transplantation that might facilitate allogenic transplantation is worth considering to treat this disease. Methods: We performed allogeneic in utero transplantation of GFP-positive myoblasts and adipose-derived mesenchymal stem cells into murine DMD model animals. The transplantation route in this study was fetal intraperitoneal transplantation and transplacental transplantation. Transplanted animals were examined at 4-weeks old by immunofluorescence staining and RT-qPCR. Results: No GFP-positive cells were found by immunofluorescence staining of skeletal muscle and no GFP mRNA was detected by RT-qPCR in any animal, transplantation method and cell type. Compared with previous reports, myoblast transplantation exhibited an equivalent mortality rate, but adipose-derived stem cell (ASC) transplantation produced a higher mortality rate. Conclusions: In utero transplantation of myoblasts or ASCs to murine models of DMD does not lead to engraftment and, in ASC transplantation primarily, frequently results in fetal death.
first_indexed 2024-04-11T14:22:30Z
format Article
id doaj.art-ba8eb31e37f24328b7308889df383856
institution Directory Open Access Journal
issn 2352-3204
language English
last_indexed 2024-04-11T14:22:30Z
publishDate 2022-12-01
publisher Elsevier
record_format Article
series Regenerative Therapy
spelling doaj.art-ba8eb31e37f24328b7308889df3838562022-12-22T04:19:00ZengElsevierRegenerative Therapy2352-32042022-12-0121486493In utero transplantation of myoblasts and adipose-derived mesenchymal stem cells to murine models of Duchenne muscular dystrophy does not lead to engraftment and frequently results in fetal deathYuki Kihara0Yukie Tanaka1Masanari Ikeda2Jun Homma3Ryo Takagi4Keiko Ishigaki5Keitaro Yamanouchi6Hiroaki Honda7Satoru Nagata8Masayuki Yamato9Department of Pediatrics, Tokyo Women’s Medical University, School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan; Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 JapanDepartment of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, JapanDepartment of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, JapanInstitute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 JapanInstitute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 JapanDepartment of Pediatrics, Tokyo Women’s Medical University, School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 JapanDepartment of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, JapanHuman Disease Models, Institute of Laboratory Animals, Tokyo Women's Medical University, Tokyo, JapanDepartment of Pediatrics, Tokyo Women’s Medical University, School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 JapanInstitute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan; Corresponding author. Fax: +81 3-3359-6046.Introduction: Duchenne muscular dystrophy (DMD) is a progressive disease that leads to damage of muscle and myocardium due to genetic abnormalities in the dystrophin gene. In utero cell transplantation that might facilitate allogenic transplantation is worth considering to treat this disease. Methods: We performed allogeneic in utero transplantation of GFP-positive myoblasts and adipose-derived mesenchymal stem cells into murine DMD model animals. The transplantation route in this study was fetal intraperitoneal transplantation and transplacental transplantation. Transplanted animals were examined at 4-weeks old by immunofluorescence staining and RT-qPCR. Results: No GFP-positive cells were found by immunofluorescence staining of skeletal muscle and no GFP mRNA was detected by RT-qPCR in any animal, transplantation method and cell type. Compared with previous reports, myoblast transplantation exhibited an equivalent mortality rate, but adipose-derived stem cell (ASC) transplantation produced a higher mortality rate. Conclusions: In utero transplantation of myoblasts or ASCs to murine models of DMD does not lead to engraftment and, in ASC transplantation primarily, frequently results in fetal death.http://www.sciencedirect.com/science/article/pii/S2352320422001006Fetal therapyIn utero transplantationMyoblastsAdipose-derived mesenchymal stem cellsDuchenne muscular dystrophy
spellingShingle Yuki Kihara
Yukie Tanaka
Masanari Ikeda
Jun Homma
Ryo Takagi
Keiko Ishigaki
Keitaro Yamanouchi
Hiroaki Honda
Satoru Nagata
Masayuki Yamato
In utero transplantation of myoblasts and adipose-derived mesenchymal stem cells to murine models of Duchenne muscular dystrophy does not lead to engraftment and frequently results in fetal death
Regenerative Therapy
Fetal therapy
In utero transplantation
Myoblasts
Adipose-derived mesenchymal stem cells
Duchenne muscular dystrophy
title In utero transplantation of myoblasts and adipose-derived mesenchymal stem cells to murine models of Duchenne muscular dystrophy does not lead to engraftment and frequently results in fetal death
title_full In utero transplantation of myoblasts and adipose-derived mesenchymal stem cells to murine models of Duchenne muscular dystrophy does not lead to engraftment and frequently results in fetal death
title_fullStr In utero transplantation of myoblasts and adipose-derived mesenchymal stem cells to murine models of Duchenne muscular dystrophy does not lead to engraftment and frequently results in fetal death
title_full_unstemmed In utero transplantation of myoblasts and adipose-derived mesenchymal stem cells to murine models of Duchenne muscular dystrophy does not lead to engraftment and frequently results in fetal death
title_short In utero transplantation of myoblasts and adipose-derived mesenchymal stem cells to murine models of Duchenne muscular dystrophy does not lead to engraftment and frequently results in fetal death
title_sort in utero transplantation of myoblasts and adipose derived mesenchymal stem cells to murine models of duchenne muscular dystrophy does not lead to engraftment and frequently results in fetal death
topic Fetal therapy
In utero transplantation
Myoblasts
Adipose-derived mesenchymal stem cells
Duchenne muscular dystrophy
url http://www.sciencedirect.com/science/article/pii/S2352320422001006
work_keys_str_mv AT yukikihara inuterotransplantationofmyoblastsandadiposederivedmesenchymalstemcellstomurinemodelsofduchennemusculardystrophydoesnotleadtoengraftmentandfrequentlyresultsinfetaldeath
AT yukietanaka inuterotransplantationofmyoblastsandadiposederivedmesenchymalstemcellstomurinemodelsofduchennemusculardystrophydoesnotleadtoengraftmentandfrequentlyresultsinfetaldeath
AT masanariikeda inuterotransplantationofmyoblastsandadiposederivedmesenchymalstemcellstomurinemodelsofduchennemusculardystrophydoesnotleadtoengraftmentandfrequentlyresultsinfetaldeath
AT junhomma inuterotransplantationofmyoblastsandadiposederivedmesenchymalstemcellstomurinemodelsofduchennemusculardystrophydoesnotleadtoengraftmentandfrequentlyresultsinfetaldeath
AT ryotakagi inuterotransplantationofmyoblastsandadiposederivedmesenchymalstemcellstomurinemodelsofduchennemusculardystrophydoesnotleadtoengraftmentandfrequentlyresultsinfetaldeath
AT keikoishigaki inuterotransplantationofmyoblastsandadiposederivedmesenchymalstemcellstomurinemodelsofduchennemusculardystrophydoesnotleadtoengraftmentandfrequentlyresultsinfetaldeath
AT keitaroyamanouchi inuterotransplantationofmyoblastsandadiposederivedmesenchymalstemcellstomurinemodelsofduchennemusculardystrophydoesnotleadtoengraftmentandfrequentlyresultsinfetaldeath
AT hiroakihonda inuterotransplantationofmyoblastsandadiposederivedmesenchymalstemcellstomurinemodelsofduchennemusculardystrophydoesnotleadtoengraftmentandfrequentlyresultsinfetaldeath
AT satorunagata inuterotransplantationofmyoblastsandadiposederivedmesenchymalstemcellstomurinemodelsofduchennemusculardystrophydoesnotleadtoengraftmentandfrequentlyresultsinfetaldeath
AT masayukiyamato inuterotransplantationofmyoblastsandadiposederivedmesenchymalstemcellstomurinemodelsofduchennemusculardystrophydoesnotleadtoengraftmentandfrequentlyresultsinfetaldeath