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Special Collection for ISSCR 2014



To complement presentations at the 2014 ISSCR Annual Meeting, STEM CELLS Translational Medicine is please to present this special collection of papers.

Tissue-Specific Progenitor and Stem Cells

Prospectively Isolated NGN3-Expressing Progenitors From Human Embryonic Stem Cells Give Rise to Pancreatic Endocrine Cells
Qing Cai, Paola Bonfanti, Rangarajan Sambathkumar, Kim Vanuytsel, Jolien Vanhove, Conny Gysemans, Maria Debiec-Rychter, Susanna Raitano, Harry Heimberg, Laura Ordovas, Catherine M. Verfaillie
Stem Cells Trans Med 2014; 3:489-499; first published on February 3, 2014; doi:10.5966/sctm.2013-0078
This study investigated whether it is possible to isolate pancreatic endocrine progenitors from differentiating human embryonic stem cell (hESC) cultures by lineage tracing of NGN3. Results indicate that NGN3+ cells represent pancreatic endocrine progenitors in humans. This hESC reporter line is a unique tool that may aid in gaining insight into the developmental mechanisms underlying fate choices in human pancreas and in developing cell-based therapies.

Tissue Engineering and Regenerative Medicine

Concise Review: In Search of Unlimited Sources of Functional Human Pancreatic Beta Cells
Raphael Scharfmann, Latif Rachdi, Philippe Ravassard
Stem Cells Trans Med 2013; 2:61-67; first published on December 19, 2012; doi:10.5966/sctm.2012-0120
Rodent and human beta cells are not identical, and knowledge of human beta cells has not progressed as quickly as understanding of rodent beta cells because of the difficulty of accessing unlimited sources of functional human pancreatic beta cells. The main focus of this review concerns recent strategies to generate new sources of human pancreatic beta cells. This knowledge would provide a strong basis for developing new treatments for diabetic patients.

Concise Review: Mesenchymal Stem Cells for Diabetes
Juan Domínguez-Bendala, Giacomo Lanzoni, Luca Inverardi, Camillo Ricordi
Stem Cells Trans Med 2012; 1:59-63; first published on December 7, 2011; doi:10.5966/sctm.2011-0017
Here we review the most current advances in the design and application of protocols for the differentiation of transplantable β-cells, with a special emphasis in analyzing MSC potency according to their tissue of origin. Although no single method appears to be ripe enough for clinical trials yet, recent progress in reprogramming (a biotechnological breakthrough that relativizes the thus far insurmountable barriers between embryonal germ layers) bodes well for the rise of MSCs as a potential weapon of choice to develop personalized therapies for type 1 diabetes.

Concise Review: Mesenchymal Stem Cells and Translational Medicine: Emerging Issues
Guangwen Ren, Xiaodong Chen, Fengping Dong, Wenzhao Li, Xiaohui Ren, Yanyun Zhang, Yufang Shi
Stem Cells Trans Med 2012; 1:51-58; first published on December 7, 2011; doi:10.5966/sctm.2011-0019
In preclinical and clinical studies, MSCs have been shown to be highly efficient in treating graft-versus-host disease, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, myocardial infarction, liver cirrhosis, inflammatory bowel disease, and other disorders. An understanding of the interaction between MSCs and the inflammatory microenvironment will provide critical information in revealing the precise in vivo mechanisms of MSC-mediated therapeutic effects and designing more practical protocols for clinical use of these cells.

Embryonic Stem Cells/Induced Pluripotent Stem (iPS) Cells

Influence of In Vitro and In Vivo Oxygen Modulation on β Cell Differentiation From Human Embryonic Stem Cells
Sirlene Cechin, Silvia Álvarez-Cubela, Jaime A. Giraldo, Ruth D. Molano, Susana Villate, Camillo Ricordi, Antonello Pileggi, Luca Inverardi, Christopher A. Fraker, Juan Domínguez-Bendala
Stem Cells Trans Med 2014; 3:277-289; first published on December 27, 2013; doi:10.5966/sctm.2013-0160
This study’s goal was to explore the role of oxygen modulation in the maturation of pancreatic progenitor (PP) cells differentiated from human embryonic stem cells. Results show that oxygen modulation contributes to enhanced maturation of PP cells and confirm its importance in the design of β-cell differentiation protocols. These findings open the door to future strategies for the transplantation of fully mature β cells.

Transgene-Free Disease-Specific Induced Pluripotent Stem Cells from Patients with Type 1 and Type 2 Diabetes
Yogish C. Kudva, Seiga Ohmine, Lucas V. Greder, James R. Dutton, Adam Armstrong, Josep Genebriera De Lamo, Yulia Krotova Khan, Tayaramma Thatava, Mamoru Hasegawa, Noemi Fusaki, Jonathan M.W. Slack, Yasuhiro Ikeda
Stem Cells Trans Med 2012; 1:451-461; first published on May 30, 2012; doi:10.5966/sctm.2011-0044
In this study, nonintegrating Sendai viral vectors were used to reprogram cells from patients with type 1 and type 2 diabetes. It was found that the Sendai vector system facilitates reliable reprogramming of patient cells into transgene-free induced pluripotent stem cells, providing a pluripotent platform for personalized diagnostic and therapeutic approaches for diabetes and diabetes-associated complications.

Concise Review: Parthenote Stem Cells for Regenerative Medicine: Genetic, Epigenetic, and Developmental Features
Brittany Daughtry, Shoukhrat Mitalipov
Stem Cells Trans Med 2014; 3:290-298; first published on January 17, 2014; doi:10.5966/sctm.2013-0127
It has been observed that embryonic stem cells have the potential to provide unlimited cells and tissues for regenerative medicine. This review suggests potential advantages and limitations of embryonic stem cells derived from parthenogenetic embryos for cell-based therapies.

Enabling Technologies for Cell-Based Clinical Translation

Transient Proteolytic Modification of Mesenchymal Stromal Cells Increases Lung Clearance Rate and Targeting to Injured Tissue
Erja Kerkelä, Tanja Hakkarainen, Tuomas Mäkelä, Mari Raki, Oleg Kambur, Lotta Kilpinen, Janne Nikkilä, Siri Lehtonen, Ilja Ritamo, Roni Pernu, Mika Pietilä, Reijo Takalo, Tatu Juvonen, Kim Bergström, Eija Kalso, Leena Valmu, Saara Laitinen, Petri Lehenkari, Johanna Nystedt
Stem Cells Trans Med 2013; 2:510-520; first published on June 3, 2013; doi:10.5966/sctm.2012-0187
This study showed that an alternative cell detachment of mesenchymal stromal/stem cells (MSCs) with pronase instead of trypsin significantly accelerated the lung clearance of the cells and, importantly, increased their targeting to an area of injury. Pronase detachment could be used as a method to improve the MSC lung clearance and targeting in vivo. This may have a major impact on the bioavailability of MSCs in future therapeutic regimes.

Signaling Adaptor Protein SH2B1 Enhances Neurite Outgrowth and Accelerates the Maturation of Human Induced Neurons
Yi-Chao Hsu, Su-Liang Chen, Ya-Jean Wang, Yun-Hsiang Chen, Dan-Yen Wang, Linyi Chen, Chia-Hsiang Chen, Hwei-Hsien Chen, Ing-Ming Chiu
Stem Cells Trans Med 2014; 3:713-722; first published on April 15, 2014; doi:10.5966/sctm.2013-0111
The authors show that SH2B adaptor protein 1β can enhance neurite outgrowth of induced neurons reprogrammed from human fibroblasts as early as day 14, when combined with miR124 and transcription factors BRN2 and MYT1L under defined conditions. These enhanced induced neurons showed canonical neuronal morphology and expressed multiple neuronal markers and functional proteins for neurotransmitter release.

Protocols and Manufacturing for Cell-Based Therapies

Activation of Human Mesenchymal Stem Cells Impacts Their Therapeutic Abilities in Lung Injury by Increasing Interleukin (IL)-10 and IL-1RN Levels
Martha L. Bustos, Luai Huleihel, Ernest M. Meyer, Albert D. Donnenberg, Vera S. Donnenberg, Joseph D. Sciurba, Lyle Mroz, Bryan J. McVerry, Bryon M. Ellis, Naftali Kaminski, Mauricio Rojas
Stem Cells Trans Med 2013; 2:884-895; first published on October 2, 2013; doi:10.5966/sctm.2013-0033
The objective of this study was to improve the protective anti-inflammatory capacity of human mesenchymal stem cells (hMSCs) by evaluating the consequences of preactivating them before use in a murine model of acute respiratory distress syndrome. It was found that the immunomodulatory capacity was better in hMSCs obtained with minimal manipulation, showing that it is possible to improve the protective anti-inflammatory capacity of hMSCs.