The Recruitment of Bone Marrow-Derived Cells to Sites of Pancreatic β-cell Injury and the Restoration of Endocrine Function

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  • IZUMIDA Yoshihiko
    <I>Department of General and Gastrointestinal Surgery, Showa Univerrsity School of Medicine</I>
  • AOKI Takeshi
    <I>Department of General and Gastrointestinal Surgery, Showa Univerrsity School of Medicine</I>
  • YASUDA Daisuke
    <I>Department of General and Gastrointestinal Surgery, Showa Univerrsity School of Medicine</I>
  • KOIZUMI Tomotake
    <I>Department of General and Gastrointestinal Surgery, Showa Univerrsity School of Medicine</I>
  • SUGANUMA Chisaki
    <I>Division of Hospital Pathology, University School of Medicine</I>
  • SAITO Koji
    <I>Division of First Pathology, Showa University School of Medicine</I>
  • MURAI Noriyuki
    <I>Department of General and Gastrointestinal Surgery, Showa Univerrsity School of Medicine</I>
  • SHIMIZU Yoshinori
    <I>Department of General and Gastrointestinal Surgery, Showa Univerrsity School of Medicine</I>
  • KUSHIMA Miki
    <I>Division of Hospital Pathology, University School of Medicine</I>
  • KUSANO Mitsuo
    <I>Department of General and Gastrointestinal Surgery, Showa Univerrsity School of Medicine</I>

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  • The Recruitment of Bone Marrow-Derived Cells to Sites of Pancreatic ^|^beta;-cell Injury and the Restoration of Endocrine Function

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Abstract

Recent studies have demonstrated that adult bone marrow cells have a tremendous capacity to differentiate into the epithelial cells of the liver, lung, gastro-intestinal tract, and pancreas. The migration of endothelial cells could also play a role in the response to pancreatic islet cell injury. To address this issue, we investigated whether transplanted bone marrow cells (BMC) have the capacity to migrate to a damaged pancreas and differentiate into insulin producing cells, thereby restoring tissue function after streptozotocin (STZ) -induced pancreatic β-cell injury in vivo. Whole bone marrow cells labeled with PKH26 were infused intravenously into syngenic STZ-treated diabetic rats. At each time point, the expression of insulin in bone marrow-derived cells was examined in immunohistochemical studies, and plasma insulin and glucose levels were measured. Donor-derived bone marrow cells were positive for insulin immunoreactivity in the recipient pancreas. In addition, bone marrow-derived cells migrated into the damaged pancreas and synthesized insulin. BMC administration partially increased the plasma insulin concentration, reduced the plasma glucose concentration, and reduced the mortality rates of STZ-treated diabetic rats. In conclusion, our study revealed that bone marrow-derived cells have a capacity for insulin production, following recruitment to the site of pancreatic β-cell injury.

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