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Human Fetal Liver Stromal Cell Co-Culture Enhances the Differentiation of Pancreatic Progenitor Cells into Islet-Like Cell Clusters

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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.

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Acknowledgments

The work described in this paper was fully supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project no. 468912), and from the School of Biomedical Sciences Group Research Grant, The Chinese University of Hong Kong (Project no. SBS-SEED-PSL), awarded to PS Leung.

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The authors declare no competing financial interest.

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Authors and Affiliations

  1. 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

    Juan Liang, Ka Yan Ng, Qianni Cheng, Yin Xia, Chi Chiu Wang & Po Sing Leung

  2. Department of Obstetrics and Gynecology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, , New Territories, Hong Kong, China

    Chi Chiu Wang

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  1. Juan Liang
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Correspondence to Po Sing Leung.

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Juan Liang and Ka Yan Ng contributed equally to this paper

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Supplemental Table 1

Primers sequences used for mRNA expression studies (DOC 76 kb)

Supplemental Table 2

Information of primary antibodies used in this study (DOC 34 kb)

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Liang, J., Ng, K.Y., Cheng, Q. et al. Human Fetal Liver Stromal Cell Co-Culture Enhances the Differentiation of Pancreatic Progenitor Cells into Islet-Like Cell Clusters. Stem Cell Rev and Rep 10, 280–294 (2014). https://doi.org/10.1007/s12015-013-9491-y

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