Impact of different pancreatic microenvironments on improvement in hyperglycemia and insulin deficiency in diabetic rats after transplantation of allogeneic mesenchymal stromal cells.

BACKGROUND: Mesenchymal stromal cells (MSCs) in the pancreatic microenvironment can improve diabetes mellitus (DM). The aim of the present study was to determine whether different pancreatic microenvironments influence the improvement of hyperglycemia and insulin deficiency. METHODS: MSCs isolated from rat bone marrow were transplanted directly into different pancreatic microenvironments in male DM rats. DM was induced in the rats by streptozotocin injection. The rats were divided into 5 groups: normal control rats, DM control rats, and 3 experimental groups (DM rats plus MSCs injected into the head of the pancreas, the tail of the pancreas, or the whole pancreas). The body weight and blood glucose of the rats were monitored during the experiment after transplantation of the MSCs. Histopathologic and immunohistochemical analyses were used to detect the presence and number of islets and insulin production in the pancreatic tissue of the rats after MSC transplantation. RESULTS: At 28 days after MSC transplantation, we observed a statistically significant decrease in the blood glucose level and an increase in weight in DM rats compared with DM control rats (P < 0.0001 and P < 0.03, respectively). A comparison of each of the DM rat groups treated with MSCs showed no significant differences in the blood glucose levels or body weight. CONCLUSION: Our results suggest that transplantation of MSCs could improve DM in the pancreatic microenvironment in an animal model with streptozotocin-induced DM. The different pancreatic areas into which the MSCs were implanted had no significant influence on the improvement in hyperglycemia and insulin deficiency.

Isolation and basic characterization of human term amnion and chorion mesenchymal stromal cells.

BACKGROUND AIMS: Emerging evidence suggests human placental membrane is a valuable source of mesenchymal stromal cells (MSC). Amnion and chorion are tissues of early embryologic origin that may entail progenitor potential. These tissues are abundantly available and ethically unobjectionable and, because they are discarded post-partum, they can be widely used for extensive research and eventually for therapeutic studies. METHODS: We looked at the cells isolated from the six amnions and chorions of term placentas of gestational weeks 39 ± 1. Isolated cells were characterized by morphologic and immunophenotypic analysis. RESULTS: With flow cytometry immunophenotype analysis, amnion- and chorion-derived cells were positive for MSC markers, and negative for hematopoietic markers. Immunocytochemical staining was positive for the embryonic cell markers Oct-3/4 and Rex-1. Oct-3/4 is a POU transcription factor that is expressed in embryonic stem (ES) cells and germ cells, and its expression is required to sustain cell self-renewal and pluripotency. Oct-3/4 is the most recognized marker for totipotent ES cells. Rex-1 is a zinc finger family transcription factor that is highly expressed in embryonic stem cells. It is one of several gene markers used to identify undifferentiated stem cells, and its expression is downregulated upon stem cell differentiation. Amnion- and chorion-derived cells were capable, under differentiation conditions, to differentiate into to mesoderm lineages. CONCLUSIONS: Phenotypic studies indicate MSC-like profiles in both amnion- and chorion-derived cells. Cells in vitro had fibroblastoid morphology. The in vitro growth behavior of such placenta-derived progenitor cells was similar to that of bone marrow MSC. Our results indicate that MSC can be easily isolated from the human term placenta. The human amniotic and chorion MSC maintained a marker profile similar to the mesenchymal progenitors and could be used for studies as an alternative source of MSC for further application in cellular therapy.