• Open Access

Concise review: Clinical programs of stem cell therapies for liver and pancreas

Authors

  • Giacomo Lanzoni,

    1. Diabetes Research Institute Miller School of Medicine, University of Miami, Miami, Florida, USA
    2. Department of Histology Embryology and Applied Biology, University of Bologna, Bologna, Italy
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  • Tsunekazu Oikawa,

    1. Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
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  • Yunfang Wang,

    1. Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
    2. The Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, People's Republic of China
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  • Cai-Bin Cui,

    1. Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
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  • Guido Carpino,

    1. Department of Health Sciences, University of Rome “ForoItalico”, Rome, Italy
    2. Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University, Rome, Italy
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  • Vincenzo Cardinale,

    1. Department of Scienze e Biotecnologie Medico-Chirurgiche, Fondazione Eleonora Lorillard Spencer Cenci, Sapienza University, Rome, Italy
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  • David Gerber,

    1. Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
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  • Mara Gabriel,

    1. MGabriel Consulting, Chapel Hill, North Carolina, USA
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  • Juan Dominguez-Bendala,

    1. Diabetes Research Institute Miller School of Medicine, University of Miami, Miami, Florida, USA
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  • Mark E. Furth,

    1. Wake Forest Innovations, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
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  • Eugenio Gaudio,

    1. Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University, Rome, Italy
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  • Domenico Alvaro,

    1. Department of Scienze e Biotecnologie Medico-Chirurgiche, Fondazione Eleonora Lorillard Spencer Cenci, Sapienza University, Rome, Italy
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  • Luca Inverardi,

    1. Diabetes Research Institute Miller School of Medicine, University of Miami, Miami, Florida, USA
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  • Lola M. Reid

    Corresponding author
    1. Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
    2. Program in Molecular Biology and Biotechnology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
    3. Lineberger Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
    • Correspondence: Lola M. Reid, Ph.D., Department of Cell Biology and Physiology and Program in Molecular Biology and Biotechnology, CB# 7038, UNC School of Medicine, Glaxo, Rm. 32-36, Chapel Hill, North Carolina 27599-7038, USA. Telephone: 919-966-0346; Fax: 919-966-6112; e-mail: Lola.M.Reid@gmail.com

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  • Author contributions: G.L.: conception and design; acquisition and assembly of data and data analyses (tables in the online supplement); interpretation; manuscript writing and editing. All art work. T.O., Y.W., C.C. J.D.: acquisition and assembly of data and data analyses (particularly the tables in the online supplement; figures; interpretation; manuscript writing and editing. G.C. V.C.: acquisition and assembly of data and figures and data analyses; interpretation; manuscript writing and editing. D.G.: manuscript writing and editing. M.F.: (senior author): literature assembly and analyses; data analyses; manuscript writing and editing. D.A.: (senior author): conception and design, assembly of data, data analyses and interpretation, manuscript writing and editing, final approval of manuscript and financial support. E.G.: (senior author): conception and design, assembly of data, data analyses and interpretation, manuscript editing, final approval of manuscript and financial support. L.R.: (senior author): conception and design, data analyses and interpretation, initial preparation of manuscript and all stages of manuscript editing, final approval of manuscript and financial support.

Abstract

Regenerative medicine is transitioning into clinical programs using stem/progenitor cell therapies for repair of damaged organs. We summarize those for liver and pancreas, organs that share endodermal stem cell populations, biliary tree stem cells (hBTSCs), located in peribiliary glands. They are precursors to hepatic stem/progenitors in canals of Hering and to committed progenitors in pancreatic duct glands. They give rise to maturational lineages along a radial axis within bile duct walls and a proximal-to-distal axis starting at the duodenum and ending with mature cells in the liver or pancreas. Clinical trials have been ongoing for years assessing effects of determined stem cells (fetal-liver-derived hepatic stem/progenitors) transplanted into the hepatic artery of patients with various liver diseases. Immunosuppression was not required. Control subjects, those given standard of care for a given condition, all died within a year or deteriorated in their liver functions. Subjects transplanted with 100-150 million hepatic stem/progenitor cells had improved liver functions and survival extending for several years. Full evaluations of safety and efficacy of transplants are still in progress. Determined stem cell therapies for diabetes using hBTSCs remain to be explored but are likely to occur following ongoing preclinical studies. In addition, mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are being used for patients with chronic liver conditions or with diabetes. MSCs have demonstrated significant effects through paracrine signaling of trophic and immunomodulatory factors, and there is limited evidence for inefficient lineage restriction into mature parenchymal or islet cells. HSCs' effects are primarily via modulation of immune mechanisms. Stem Cells 2013;31:2047–2060

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