title: Human fetal liver stromal cell co-culture enhances the differentiation of pancreatic progenitor cells into islet-like cell clusters.
abstract: Recent advance in directed differentiation of pancreatic stem cells offers potential to the development of replacement therapy for diabetic patients. However, the existing differentiation protocols are complex, time-consuming, and costly; thus there is a need for alternative protocols. Given the common developmental origins of liver and pancreas, we sought to develop a novel protocol, devoid of growth factors, by using liver stromal cells (LSCs) derived from human fetal liver. We examined the effects of the LSCs on the differentiation of pancreatic progenitor cells (PPCs) into islet-like cell clusters (ICCs). PPCs and LSCs isolated from 1st to 2nd trimester human fetal tissues underwent co-cultures; differentiation and functionality of ICCs were determined by examining expression of critical markers and secretion of insulin. Co-culture with 2nd but not 1st trimester LSCs enhanced ICC differentiation and functionality without the use of exogenous differentiation 'cocktails'. Differential expression profiles of growth factors from 1st versus 2nd trimester fetal liver were compared. Many morphogenic factors were expressed by LSCs, while insulin-like growth factor 1 (IGF1) was identified as one of the key molecules responsible for the ICC differentiation. This is the first report showing that an LSC-induced microenvironment can enhance ICC differentiation and functionality. Further modifications of the stroma microenvironment may offer an alternative, efficient and cost-effective approach to providing islets for transplantation.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Room 609A, Lo Kwee-Seong Integrated Biomedical Sciences Building, Shatin, , New Territories, Hong Kong, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liang
authors.forename: Ka Yan
authors.initials: KY
authors.lastname: Ng
authors.forename: Qianni
authors.initials: Q
authors.lastname: Cheng
authors.forename: Yin
authors.initials: Y
authors.lastname: Xia
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Wang
authors.forename: Po Sing
authors.initials: PS
authors.lastname: Leung
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation; D008099:Liver / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude; D013234:Stem Cells / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology; D055411:TGF-beta Superfamily Proteins / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; C583557:IGF1 protein, human; D055411:TGF-beta Superfamily Proteins; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I