Early E-Pub (#17)

Cell Transplantation
The Regenerative Medicine Journal

EPC-secreted factors favorably impact on pancreatic islet cell cotransplantation
Enhancing pancreatic islet transplantation with EPCs

Putnam Valley, NY (November 25, 2013)—Pancreatic islet transplantation is a promising therapy for treating type 1 diabetes, but the majority of transplanted cells die soon after they are transplanted. Researchers interested in prolonging the life of these cells cotransplanted endothelial progenitor cells (EPCs) along with pancreatic islet cells and found that the EPCs improved the engraftment of pancreatic islet cells in mouse models, thereby favorably impacting on the cure rate and glycemic control of transplanted islets.

The study will be published in a future issue of Cell Transplantation but is currently freely available online as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT1021Penko

“EPCs are a promising candidate for improving outcomes in islet transplantation and their mechanisms warrant further study,” said study coauthor Dr. Claire Jessup of the Department of Human Physiology at the Flinders University School of Medicine in Bedford Park, Australia. “Our study indicates that EPCs or their soluble products modulate the expression of the β-cell surface molecule connexion 36 and affect glucose-stimulated insulin release.”

According to the researchers, EPCs are a circulating bone marrow cell that are able to home to sites of damaged tissue or ischemia and can participate in wound healing and rebuilding blood vessels, especially after transplantation.  Although EPCs have the ability to integrate into newly growing blood vessels, they can also provide humoral factors (elements in blood or other fluids) that may “recruit” other cells to impact favorably on vascular remodeling. This study planned on exploring how EPCs secreted humoral factors and how those factors may impact pancreatic islet cell gene expression and function and thus aid islet cell survival following transplantation.

“As a conduit for blood supply, intraislet vasculature is crucial for the delivery of oxygen, the sensing of blood glucose, dissemination of insulin and removal of waste products,” said Jessup. “Also, within the islet cell, endothelial cells are in intimate contact with beta cells and directly enhance insulin transcription, secretion and stimulate β-cell proliferation.”

In this study, diabetic mice were transplanted with cultured islets. The researchers were interested in whether EPCs can replenish the endothelial cells that are lost during culture and so they used islets that had been cultured in vitro for 3 days prior to transplantation. The authors defined a ‘cure of diabetes’ as the first day of two low, consecutive nonfasted blood glucose readings with no subsequent reversion to hyperglycemia.

The mice were monitored daily for nonfasted blood glucose and body weight. There was a significantly improved cure rate in cotransplanted animals as compared to controls that did not receive EPCs.

“Revascularization in the mouse occurs within 14 days posttransplantation,” explained Jessup. “Following the expected revascularisation period, the percentage of cure in cotransplanted animals at day 14 was 83%, as compared to 20% in the islets-only control group. There was significantly improved posttransplant weight gain in the mice receiving cotransplanted EPCs compared to mice receiving islets alone.”

The research team concluded that further mechanistic research was required, but that cell surface molecules involved in intraislet communication, such as connexin 36, may represent important clinical targets in the future.

“This study proposes that EPCs and/or their secretagogues aid islet survival following transplantation via cell surface molecules” said Dr. Rodolfo Alejandro, section editor for Cell Transplantation and Professor of Medicine at the University of Miami Miller School of Medicine. “This is a promising arena of study that requires additional research to determine its potential”

Contact: Dr. Claire F. Jessup, Room 6E101, Department of Human Physiology, School of Medicine, Flinders University of SA, Bedford Park, SA 5042 Australia. Tel: + 61 (8) 8204 3960; Fax:  +61 (8) 8204 5768; Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Citation: Penko, D.; Rojas‐Canales, D.; Mohanasundaram, D.; Peiris, H. S.; Sun, W. Y.; Drogemuller, C. J.; Keating, D. J.; Coates,  P. T. H.; Bonder, C. S.;  Jessup, C. F. Endothelial progenitor cells enhance islet engraftment, influence beta cell function and modulate islet connexin 36 expression. Cell Transplant. Appeared or available online: September 10, 2013.

The Coeditors-in-chief for CELL TRANSPLANTATION are at the Diabetes Research Institute, University of Miami Miller School of Medicine and Center for Neuropsychiatry, China Medical University Hospital, TaiChung, Taiwan. Contact, Camillo Ricordi, M.D. at This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Shinn-Zong Lin, M.D., Ph.D. at This e-mail address is being protected from spambots. You need JavaScript enabled to view it or David Eve, Ph.D. at This e-mail address is being protected from spambots. You need JavaScript enabled to view it

News release by Florida Science Communications www.sciencescribe.net

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