title: Transplantation of heterospheroids of islet cells and mesenchymal stem cells for effective angiogenesis and antiapoptosis.
abstract: Although islet transplantation has been suggested as an alternative therapy for type 1 diabetes, there are efficiency concerns that are attributed to poor engraftment of transplanted islets. Hypoxic condition and delayed vasculogenesis induce necrosis and apoptosis of the transplanted islets. To overcome these limitations in islet transplantation, heterospheroids (HSs), which consist of rat islet cells (ICs) and human bone marrow-derived mesenchymal stem cells (hMSCs), were transplanted to the kidney and liver. The HSs cultured under the hypoxic condition system exhibited a significant increase in antiapoptotic gene expression in ICs. hMSCs in the HSs secreted angiogenic and antiapoptotic proteins. With the HS system, ICs and hMSCs were successfully located in the same area of the liver after transplantation of HSs through the portal vein, whereas the transplantation of islets and the dissociated hMSCs did not result in localization of transplanted ICs and hMSCs in the same area. HS transplantation resulted in an increase in angiogenesis at the transplantation area and a decrease in the apoptosis of transplanted ICs after transplantation into the kidney subcapsule compared with transplantation of islet cell clusters (ICCs). Insulin production levels of ICs were higher in the HS transplantation group compared with the ICC transplantation group. The HS system may be a more efficient transplantation method than the conventional methods for the treatment of type 1 diabetes.
authors.affiliation: 1 School of Chemical and Biological Engineering, Seoul National University , Seoul, Republic of Korea.
authors.forename: Jung-Youn
authors.initials: JY
authors.lastname: Shin
authors.forename: Jee-Heon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Bhang
authors.forename: Gun-Jae
authors.initials: GJ
authors.lastname: Jeong
authors.forename: Muhammad R
authors.initials: MR
authors.lastname: Haque
authors.forename: Taslim A
authors.initials: TA
authors.lastname: Al-Hilal
authors.forename: Myungkyung
authors.initials: M
authors.lastname: Noh
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D002449:Cell Aggregation; D002452:Cell Count; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000166:cytology; D008099:Liver / Q000166:cytology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018919:Neovascularization, Physiologic; D011169:Portal Vein / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018874:Spheroids, Cellular / Q000166:cytology*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007328:Insulin; D012333:RNA, Messenger