title: Two distinct mechanisms mediate the involvement of bone marrow cells in islet remodeling: neogenesis of insulin-producing cells and support of islet recovery.
abstract: We have recently reported that small-sized bone marrow cells (BMCs) isolated by counterflow centrifugal elutriation 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 hematopoietic progenitors (R/O) and whole BMCs in a murine model of streptozotocin-induced chemical diabetes. The GFP(bright)CD45(+) 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 GFP(dim)CD45(-)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 synergistic mechanisms that contribute to islet recovery from injury: support of islet remodeling by hematopoietic cells and neogenesis of insulin-producing cells from stem cells.
authors.affiliation: Frankel Laboratory, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Iskovich
authors.forename: Nitza
authors.initials: N
authors.lastname: Goldenberg-Cohen
authors.forename: Tamila
authors.initials: T
authors.lastname: Sadikov
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
authors.forename: Jerry
authors.initials: J
authors.lastname: Stein
authors.forename: Nadir
authors.initials: N
authors.lastname: Askenasy
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018183:Transplantation Chimera / Q000378:metabolism*