Endocrine cell and nerve regeneration in autologous in situ tissue-engineered small intestine.
BACKGROUND
The purpose of this study was to regenerate a larger size of small intestinal tissue than that of our previous study and to evaluate the regeneration of the endocrine cells (ECC) and nerve system of autologous tissue-engineered small intestine. The effect of implantation of large numbers of smooth muscle cells (SMC) for the regeneration of small intestine was also investigated.


METHODS
Two types of scaffolds with different cell densities were fabricated: low density (LD) of SMC in the scaffold and high density (HD) of SMC in the scaffold. Both scaffolds were implanted into defects of isolated ileum in a canine model. Animals were sacrificed at 8, 12, 18, and 24 weeks.


RESULTS
The area of engineered small intestine in the HD group was four times larger than that in the LD group, although that was smaller in size than the original size of the defect. There were no significant changes in the thickness of regenerated smooth muscle layer (SML) in the LD and HD groups. The numbers of endocrine cells gradually increased after implantation. At 18 weeks of regeneration, the number of ECC reached levels comparable to that of normal mucosa. The nerve fibers extended to the center of the graft area and were observed in regenerated SML and regenerated villi at 24 weeks.


CONCLUSIONS
The ECC and nerve fibers were regenerated in autologous in situ tissue-engineered small intestine. Seeding a large number of SMC was not sufficient for the regeneration of the small intestine in a tubular configuration.
Nakase
Yuen
Y
Department of Surgery and Regenerative Medicine, Division of Surgery and Physiology of Digestive System, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. yuen-n@koto.kpu-m.ac.jp
Nakamura
Tatsuo
T
Kin
Syuichi
S
Nakashima
Susumu
S
Yoshikawa
Tetsuji
T
Kuriu
Yoshiaki
Y
Miyagawa
Kouji
K
Sakakura
Chohei
C
Otsuji
Eigo
E
Ikada
Yoshihito
Y
Yamagishi
Hisakazu
H
Hagiwara
Akeo
A
D000818:Animals; D001672:Biocompatible Materials; D002452:Cell Count; D004285:Dogs; D017615:Enteric Nervous System / Q000166:cytology / Q000502:physiology*; D005260:Female; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology; D007421:Intestine, Small / Q000166:cytology / Q000294:innervation / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D009416:Nerve Regeneration / Q000502:physiology*; D009490:Neurosecretory Systems / Q000166:cytology / Q000502:physiology; D009852:Omentum; D012778:Short Bowel Syndrome / Q000601:surgery; D012825:Silicon; D023822:Tissue Engineering / Q000379:methods*
D001672:Biocompatible Materials; D012825:Silicon