Bioengineering of a functional sheet of islet cells for the treatment of diabetes mellitus.
The present study was designed to establish a novel tissue engineering approach for diabetes mellitus (DM) by fabricating a tissue sheet composed of pancreatic islet cells for in vivo transplantation. Pancreatic islet cell suspensions were obtained from Lewis rats, and plated onto temperature-responsive culture dishes coated with extracellular matrix (ECM) proteins. After the cells reached confluency, islet cells cultured on laminin-5 coated dishes were successfully harvested as a uniformly spread tissue sheet by lowering the culture temperature to 20 degrees C for 20 min. The functional activity of the islet cell sheets was confirmed by histological examination and Insulin secretion assay prior to in vivo transplantation. Histological examination revealed that the harvested islet cell sheet was comprised of insulin- (76%) and glucagon- (19%) positive cells, respectively. In vivo functionality of the islet cell sheet was maintained even 7 days after transplantation into the subcutaneous space of Lewis rats. The present study describes an approach to generate a functional sheet of pancreatic islet cells on laminin-5 coated temperature-responsive dishes, which can be subsequently transplanted in vivo. This study serves as the foundation for the creation of a novel cell-based therapy for DM to provide patients an alternative method.
Shimizu
Hirofumi
H
Department of Surgery 1, Fukushima Medical University, Fukushima, Japan.
Ohashi
Kazuo
K
Utoh
Rie
R
Ise
Kazuya
K
Gotoh
Mitsukazu
M
Yamato
Masayuki
M
Okano
Teruo
T
D000818:Animals; D015815:Cell Adhesion Molecules / Q000737:chemistry; D017690:Cell Transplantation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000628:therapy*; D005109:Extracellular Matrix / Q000378:metabolism; D005934:Glucagon / Q000737:chemistry / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000295:instrumentation* / Q000379:methods*; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D013696:Temperature; D013997:Time Factors; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D005934:Glucagon; D007328:Insulin; D000097794:Kalinin