Regeneration of the rat neonatal intestine in transplantation.
OBJECTIVE
Based on development of stem cell technology, newborn tissue, even undergoing cryopreservation, possesses promising potential as a donor source in the field of organ transplantation. However, the precise regeneration processes remains unclear. This study was designed to investigate the regenerative potential of newborn intestine with or without cryopreservation in the transplantation.


METHODS
Newborn rat intestines with or without cryopreservation were transplanted subcutaneously into the syngeneic host, and specimens were evaluated by histology, multiple immunostaining, and comprehensive gene expression analysis.


RESULTS
We determined that newborn rat intestine possessed regenerative potential in the syngeneic host even after cryopreservation, where angiogenesis was induced early in the submucosa with subsequent maturation in the crypts. Furthermore, newborn intestinal graft could facilitate the survival of maturation-incompetent 10-day-old graft that lacked regenerating activity (P < 0.01, n = 13). Tissue aggregates from the maturation-incompetent graft underwent reconstitution of their histologic configuration in the presence of newborn intestinal aggregates. Comprehensive gene expression analysis showed that 37 genes were preferentially up-regulated, while 19 genes were down-regulated in the regenerating 10-day-old graft (supported by the newborn graft).


CONCLUSIONS
Regeneration of newborn intestine is implicated in neo-angiogenesis in the host, and the newborn intestinal graft is capable of mediating the survival of the maturation-incompetent 10-day-old graft. Notwithstanding ethical and legal limitations in the clinic, these results may provide new insights into the regenerative role of newborn grafts.
Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical School, Tochigi, Japan.
Kazunori
K
Tahara
Takashi
T
Murakami
Jun
J
Fujishiro
Masafumi
M
Takahashi
Seiichiro
S
Inoue
Kohei
K
Hashizume
Kenjiro
K
Matsuno
Eiji
E
Kobayashi
D000818:Animals; D000831:Animals, Newborn; D001707:Biopsy, Needle; D015925:Cryopreservation / Q000379:methods; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000473:pathology / Q000502:physiology* / Q000637:transplantation*; D051381:Rats; D011917:Rats, Inbred Lew; D012038:Regeneration / Q000502:physiology*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013997:Time Factors; D016378:Tissue Transplantation / Q000379:methods; D014181:Transplantation Immunology; D014184:Transplantation, Homologous