Cell sheet transplantation for in utero cellular repair of fetal myelomeningocele
Ubaidus Sobhan, B.D.S, Ph.D.
1
1, 2
, Rie Ishii, M.D.
1, 3
, Tatsuzo Hebiguchi, M.D.
1
1, 3
5
, Matsui Makoto, Ph.D. ,
5
Tomoo Sato, Ph.D. , Hiromasa Yamashita, Ph.D. , Yasuhiko Tabata, PhD. , Toshio Chiba, M.D, Ph.D.
1
National Center for Child Health and Development, Clinical Research Center, Tokyo, Japan,
Dental College, Department of Physiology, Tokyo, Japan,
Surgery, Tokyo, Japan,
4
3
2
1
Tokyo
Showa University, Department of Pediatric
The University of Tokyo, Department of Machano-informatics, Tokyo, Japan, 5
Institute for frontier Medical Science. Kyoto University, Kyoto, Japan
Myelomeningocele (MMC) is a devastating disability with significant morbidity within the
first few decades of life. The objective of our study is to evaluate therapeutic feasibility
of cell sheet (myoblast in origin) transplantation for prenatal recovery of damaged neural
tissues of fetal MMC.
This technology employs a “thermo-responsive culture dish” which enables to detach a
cell sheet from the dish base by controlling its thermo-hydrophobicity. The cell sheet has
been medically tested so far for regeneration of diverse tissues including myocardium,
corneal epithelium, esophagus, lung, liver, pancreas, thyroid, and periodontium. This
study is the first one, which uses cell sheet for fetal regeneration of the damaged neural
tissue of MMC.
Experimentally, lumbosacral MMC lesions were induced by enforced oral administration
of retinoic acid in olive oil to pregnant rats at a dose of 60mg/kg/body weight (at E-21
days).
High-resolution micro-CT was used to diagnose those pregnant rats as having
fetal MMC at E-19 days. As early as 4 hrs after the transplantation with hysterotomy,
attachment of the cell sheet was demonstrated histochemically with positive myoblast
markers including neural growth factors at the transplanted region. Currently, in place of
the cell sheet, we hope a gelatin composite sheet could work better as a new modality in
terms of technical facilitation of the procedure with an improved durability of the sheet
even under a specific underwater environment (in amniotic fluid).
E