Cell Medicine 2(3) Abstracts

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Cell Medicine, Vol. 2, pp. 86–96, 2012
2155-1790/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517911X 617888
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Resident Endothelial Progenitor Cells From Human Placenta Have Greater Vasculogenic Potential Than Circulating Endothelial Progenitor Cells From Umbilical Cord Blood

Brian M. Rapp,* M. Reza Saadatzedeh,*† Richard H. Ofstein,* Janak R. Bhavsar,*† Zachary S. Tempel,‡ Oscar Moreno,* Peter Morone,‡ Dana A. Booth,* Dmitry O. Traktuev,†§ Michael C. Dalsing,* David A. Ingram,¶# Mervin C. Yoder,¶# Keith L. March,†§** and Michael P. Murphy*†**

*Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
†Indiana Center for Vascular Biology and Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
‡Indiana University School of Medicine, Indianapolis, IN, USA
§Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
¶Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA
#Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA
**Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA

Endothelial colony-forming cells (ECFCs) isolated from umbilical cord blood (CBECFCs) are highly proliferative and form blood vessels in vivo. The purpose of this investigation was to isolate and characterize a population of resident ECFCs from the chorionic villi of term human placenta and provide a comparative analysis of their proliferative and vasculogenic potential with CBECFCs. ECFCs were isolated from umbilical cord blood and chorionic villi from placentas obtained by caesarean deliveries. Placental ECFCs (PECFCs) expressed CD144, CD31, CD105, and KDR and were negative for CD45 and CD34, consistent with other ECFC phenotypes. PECFCs were capable of 28.6 ± 6.0 population doublings before reaching senescence (vs. 47.4 ± 3.2 for CBECFCs, p < 0.05, n = 4). In single cell assays, 46.5 ± 1.2% underwent at least one division (vs. 51.0 ± 1.8% of CBECFCs, p = 0.07, n = 6), and of those dividing PECFCs, 71.8 ± 0.9% gave rise to colonies of >500 cells (highly proliferative potential clones) over 14 days (vs. 69.4 ± 0.7% of CBECFCs, p = 0.07, n = 9). PECFCs formed 5.2 ± 0.8 vessels/mm2 in collagen/fibronectin plugs implanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, whereas CBECFCs formed only 1.7 ± 1.0 vessels/mm2 (p < 0.05, n = 4). This study demonstrates that circulating CBECFCs and resident PECFCs are identical phenotypically and contain equivalent quantities of high proliferative potential clones. However, PECFCs formed significantly more blood vessels in vivo than CBECFCs, indicating that differences in vasculogenic potential between circulating and resident ECFCs exist.

Key words: Vascular endothelial cells; Endothelial progenitor cells; Placenta; Vasculogenesis; Pluripotent stem cells

Received March 24, 2011; final acceptance September 25, 2011. Online prepub date: December 9, 2011.
Address correspondence to Michael P. Murphy, M.D., Assistant Professor of Surgery, Department of Surgery, Indiana University School of Medicine, 1801 N. Senate Blvd., MPC2, #3500, Indianapolis, IN 46202-1228, USA. Tel: (317) 630-8288; Fax: (317) 962-0289; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 2, pp. 97–104, 2012
2155-1790/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517911X617905
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Validation of Islet Transport From a Geographically Distant Isolation Center Enabling Equitable Access and National Health Service Funding of a Clinical Islet Transplant Program for England

Ali Aldibbiat,* Guo Cai Huang,† Min Zhao,† Graham N. Holliman,* Linda Ferguson,* Stephen Hughes,‡ Ken Brigham,§ Julie Wardle,¶ Rob Williams,¶ Anne Dickinson,§ Steven A. White,*¶ Paul R. V. Johnson,‡ Derek Manas,*¶ Stephanie A. Amiel,† and James A. M. Shaw*

*Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
†Division of Diabetes and Nutritional Sciences, King’s College London, London, UK
‡Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
§Department of Haematology, Newcastle University, Newcastle upon Tyne, UK
¶Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK

Islet transplantation has become established as a successful treatment for type 1 diabetes complicated by recurrent severe hypoglycemia. In the UK access has been limited to a few centrally located units. Our goal was to validate a quality-assured system for safe/effective transport of human islets in the UK and to successfully undertake the first transplants with transported islets. Pancreases were retrieved from deceased donors in the north of England and transported to King’s College London using two-layer method (TLM) or University of Wisconsin solution alone. Islets were isolated and transported back to Newcastle in standard blood transfusion or gas-permeable bags with detailed evaluation pre- and posttransport. In the preclinical phase, islets were isolated from 10 pancreases with mean yield of 258,000 islet equivalents. No significant differences were seen between TLM and University of Wisconsin solution organ preservation. A significant loss of integrity was demonstrated in islets shipped in gas-permeable bags, whereas sterility, number, purity, and viability were maintained in blood transfusion bags. Maintenance of secretory granules and glucose-stimulated insulin secretion was confirmed following transport. A Standard Operating Procedure enabling final pretransplant quality control from a simple side-arm sample was validated. Moreover, levels of insulin and cytokines in transport medium were low, enabling transplant without centrifugation/resuspension at the recipient site. Six clinical transplants of transported islets were undertaken in five recipients with 100% primary graft function and resolution of severe hypoglycemia. Safe and clinically effective islet transport has been established facilitating sustainable NHS funding of a clinical islet transplant program for the UK.

Key words: Islet transplant; Islet isolation; Islet transport; Type 1 diabetes; Glucose-stimulated insulin secretion

Received March 15, 2011; final acceptance September 10, 2011. Online prepub date: December 9, 2011.
Address correspondence to Professor James A. M. Shaw, Institute of Cellular Medicine, 4th Floor William Leech Building, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. Tel: +44 191 222 7019; Fax: +44 191 222 0723; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 2, pp. 105–110, 2012
2155-1790/12 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517911X617897
Copyright © 2012 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Brief Communication

Hypothermic Perfusion Preservation of Pancreas for Islet Grafts: Validation Using a Split Lobe Porcine Model

B. P. Weegman,* M. J. Taylor,† S. C. Baicu,† W. E. Scott, III,* K. R. Mueller,* J. D. Kitzmann,* M. D. Rizzari,* and K. K. Papas*

*Shultze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, USA
†Cell and Tissue Systems Inc., N. Charleston, SC, USA

The demand for high-quality islets for transplantation in type I diabetics will increase as the current clinical trials transition into standard of care. The mode of preservation of donor pancreata is critical to this mission since islets are very sensitive to ischemic injury. Hypothermic perfusion preservation (HPP) is being investigated for extended pancreas preservation in light of the beneficial effects reported for other organs. The present pilot study aimed to establish the potency of porcine islets isolated from pancreata after 24 h of HPP at 4–8°C. The study design included a split-lobe pancreas model that permitted paired comparisons of islets isolated from 24-h HPP splenic lobes with nonperfused, fresh control duodenal/connecting lobes stored at 4°C for <3 h. Prior to transplantation, islet viability was assessed in vitro using the ratio of oxygen consumption rate to DNA (OCR/DNA) assay and correlated with subsequent in vivo function by transplantation in diabetic immunodeficient mice. The OCR/DNA (mean ± SD) measured after 7 days of culture and immediately prior to transplantation for islets from the 24-h HPP group was 269 ± 19 nmol/min/mg DNA, which was higher but not statistically different to the mean of 236 ± 43 for the counterpart control group. All four nude mice transplanted with islets from the 24-h HPP group showed diabetes reversal, compared with five of six transplants from the control group. In conclusion, islets isolated from adult porcine pancreata after 24-h HPP exhibited high viability as measured by OCR/DNA and were able to consistently reverse diabetes in a nude mouse bioassay.

Key words: Perfusion; Pancreas; Islet; Oxygen consumption; Viability; Hypothermic perfusion

Received April 21, 2011; final acceptance September 2, 2011. Online prepub date: December 12, 2011.
Address correspondence to Michael J. Taylor, Ph.D., VP Research and Development, Cell and Tissue Systems, Inc., 2231 Technical Parkway, Suite A, N. Charleston, SC 29406, USA. Tel: (843)722-6756; Fax: (843) 722-6657; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it