Two distinct mechanisms mediate the involvement of bone marrow cells in islet remodeling: Neogenesis of insulin-producing cells and support of islet recovery

Svetlana Iskovich, Nitza Goldenberg-Cohen, Tamila Sadikov, Isaac Yaniv, Jerry Stein, Nadir Askenasy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We have recently reported that small-sized bone marrow cells (BMCs) isolated by counterflow centrifugal elutri-ation and depleted of lineage markers (Fr25lin-) have the capacity to differentiate and contribute to regeneration of injured islets. In this study, we assess some of the characteristics of these cells compared to elutriated hema-topoietic progenitors (R/O) and whole BMCs in a murine model of streptozotocin-induced chemical diabetes. The GFPbrightCD45+ progeny of whole BMCs and R/O progenitors progressively infiltrate the pancreas with evolution of donor chimerism; are found at islet perimeter, vascular, and ductal walls; and have a modest impact on islet recovery from injury. In contrast, Fr25lin- cells incorporate in the islets, convert to GFPdimCD45-PDX-1+ phenotypes, produce proinsulin, and secrete insulin with significant contribution to stabilization of glucose homeostasis. The elutriated Fr25lin- cells express low levels of CD45 and are negative for SCA-1 and c-kit, as removal of cells expressing these markers did not impair conversion to produce insulin. BMCs mediate two syn-ergistic mechanisms that contribute to islet recovery from injury: support of islet remodeling by hematopoietic cells and neogenesis of insulin-producing cells from stem cells.

Original languageEnglish
Pages (from-to)879-890
Number of pages12
JournalCell Transplantation
Volume24
Issue number5
DOIs
StatePublished - 1 Jan 2015
Externally publishedYes

Keywords

  • Bone marrow stem cells
  • Bone marrow transplantation
  • Chemical diabetes
  • Hematopoietic progenitors
  • Insulin-producing cells
  • Islet remodeling
  • β-Cell regeneration

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