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The Programmable Cell of Monocytic Origin (PCMO): A Potential Adult Stem/Progenitor Cell Source for the Generation of Islet Cells

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The Islets of Langerhans

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 654))

Abstract

Adult stem or programmable cells hold great promise in diseases in which damaged or non-functional cells need to be replaced, such as in type 1 diabetes. We have recently demonstrated that peripheral blood monocytes can be differentiated in vitro into pancreatic β-cell-like cells capable of synthesizing insulin. The two-step phenotypic conversion commences with growth factor-induced partial reprogramming during which the cells acquire a state of plasticity along with expression of various markers of pluripotency. These cells, termed “programmable cells of monocytic origin” (PCMOs), can then be induced with appropriate differentiation media to become insulin-producing cells (NeoIslet cells). Expression profiling of transcription factors known to determine endocrine and β-cell development in vivo indicated that NeoIslet cells resemble cells with an immature β-cell phenotype. Current efforts focus on establishing culture conditions that (i) increase the plasticity and proliferation potential of PCMOs by enhancing the reprogramming process and (ii) improve insulin production by mimicking in vivo lineage specification and normal pancreatic endocrine development. Combining these two strategies has great potential in generating large amounts of blood-derived cells suitable for both autologous and allogeneic therapy of type 1 diabetes.

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Abbreviations

BMP:

bone morphogenetic protein

EGF:

epidermal growth factor

FGF:

fibroblast growth factor

ESC:

embryonic stem cell

IL-3:

interleukin-3

HGF:

hepatocyte growth factor

M-CSF:

macrophage colony-stimulating factor

MSC:

mesenchymal stem cell

PCMO:

programmable cell of monocytic origin

RA:

retinoic acid

RT-PCR:

reverse transcription polymerase chain reaction

Shh:

sonic hedgehog

TGF-beta:

transforming growth factor-beta

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Acknowledgements

We are indebted to Dr. M. Schulze for long-standing intellectual support. We acknowledge not citing many original publications directly, but rather through the reviews. Part of the work described here was supported by Blasticon Biotechnologische Forschung and Fresenius Biotech.

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Authors and Affiliations

  1. Clinic for Applied Cellular Medicine, UKS-H, Campus Kiel, 24105, Kiel, Germany

    Hendrik Ungefroren

  2. Clinic for Applied Cellular Medicine, UKS-H, Campus Kiel, Arnold-Heller Str. 3 (Haus 18), 24105, Kiel, Germany

    Fred Fändrich

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  1. Hendrik Ungefroren
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  2. Fred Fändrich
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Correspondence to Hendrik Ungefroren .

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Editors and Affiliations

  1. Dept. Clinical Research & Education, Karolinska Institutet, Stockholm, 118 83, Sweden

    Md. Shahidul Islam

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Ungefroren, H., Fändrich, F. (2010). The Programmable Cell of Monocytic Origin (PCMO): A Potential Adult Stem/Progenitor Cell Source for the Generation of Islet Cells. In: Islam, M. (eds) The Islets of Langerhans. Advances in Experimental Medicine and Biology, vol 654. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3271-3_29

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