PMID- 24380400 OWN - NLM STAT- MEDLINE DCOM- 20160125 LR - 20150507 IS - 1555-3892 (Electronic) IS - 0963-6897 (Linking) VI - 24 IP - 5 DP - 2015 TI - Two distinct mechanisms mediate the involvement of bone marrow cells in islet remodeling: neogenesis of insulin-producing cells and support of islet recovery. PG - 879-90 LID - 10.3727/096368913X676899 [doi] AB - 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. FAU - Iskovich, Svetlana AU - Iskovich S AD - Frankel Laboratory, Schneider Children's Medical Center of Israel, Petach Tikva, Israel. FAU - Goldenberg-Cohen, Nitza AU - Goldenberg-Cohen N FAU - Sadikov, Tamila AU - Sadikov T FAU - Yaniv, Isaac AU - Yaniv I FAU - Stein, Jerry AU - Stein J FAU - Askenasy, Nadir AU - Askenasy N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131230 PL - United States TA - Cell Transplant JT - Cell transplantation JID - 9208854 SB - IM MH - Animals MH - Bone Marrow Cells/*metabolism MH - *Bone Marrow Transplantation MH - *Cell Differentiation MH - Diabetes Mellitus, Experimental/metabolism/*therapy MH - Insulin-Secreting Cells/*metabolism MH - Mice MH - Mice, Transgenic MH - Transplantation Chimera/*metabolism EDAT- 2014/01/02 06:00 MHDA- 2016/01/26 06:00 CRDT- 2014/01/02 06:00 PHST- 2014/01/02 06:00 [entrez] PHST- 2014/01/02 06:00 [pubmed] PHST- 2016/01/26 06:00 [medline] AID - content-ct1082Iskovich [pii] AID - 10.3727/096368913X676899 [doi] PST - ppublish SO - Cell Transplant. 2015;24(5):879-90. doi: 10.3727/096368913X676899. Epub 2013 Dec 30.