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Stem Cell Res. 2016 Jan;16(1):40-53. doi: 10.1016/j.scr.2015.11.015. Epub 2015 Nov 30.

Cells with surface expression of CD133highCD71low are enriched for tripotent colony-forming progenitor cells in the adult murine pancreas.

Author information

1
Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States; State Key Laboratory of Natural Medicines, Biopharmaceutical College, China Pharmaceutical University, Tongjia Xiang 24, Nanjing, 210009, People's Republic of China.
2
Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
3
Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Irell & Manella Graduate School of Biological Sciences, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
4
Department of Bioengineering, California Institute of Technology, Pasadena, CA 91125, United States.
5
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, United States.
6
Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Irell & Manella Graduate School of Biological Sciences, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States. Electronic address: hku@coh.org.

Abstract

Progenitor cells in the adult pancreas are potential sources of endocrine beta cells for treating type 1 diabetes. Previously, we identified tri-potent progenitor cells in the adult (2-4month-old) murine pancreas that were capable of self-renewal and differentiation into duct, acinar, and endocrine cells in vitro. These progenitor cells were named pancreatic colony-forming units (PCFUs). However, because PCFUs are a minor population in the pancreas (~1%) they are difficult to study. To enrich PCFUs, strategies using cell-surface marker analyses and fluorescence-activated cell sorting were developed. We found that CD133(high)CD71(low) cells, but not other cell populations, enriched PCFUs by up to 30 fold compared to the unsorted cells. CD133(high)CD71(low) cells generated primary, secondary, and subsequent colonies when serially re-plated in Matrigel-containing cultures, suggesting self-renewal abilities. In the presence of a laminin hydrogel, CD133(high)CD71(low) cells gave rise to colonies that contained duct, acinar, and Insulin(+)Glucagon(+) double-hormonal endocrine cells. Colonies from the laminin hydrogel culture were implanted into diabetic mice, and five weeks later duct, acinar, and Insulin(+)Glucagon(-) cells were detected in the grafts, demonstrating tri-lineage differentiation potential of CD133(high)CD71(low) cells. These CD133(high)CD71(low) cells will enable future studies of putative adult pancreas stem cells in vivo.

KEYWORDS:

Differentiation; Fluorescence-activated cell sorting (FACS); Heterogeneity of ductal cells; Pancreatic colony-forming units; Self-renewal

PMID:
26691820
PMCID:
PMC4762724
DOI:
10.1016/j.scr.2015.11.015
[Indexed for MEDLINE]
Free PMC Article

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