McEwen Monthly

iPS Cell Reprogramming is Associated with Genetic Abnormalities

Copy number variations (CNVs) are alterations of DNA in which a region of the genome is either deleted or amplified on certain chromosomes.Dr. Andras Nagy’s laboratory and Dr. Timo Otonkoski’s laboratory (Biomedicum Stem Cell Center, University of Helsinki), in collaboration with researchers in Canada and Europe, have identified genetic abnormalities associated with reprogramming adult cells to induced pluripotent stem cells (iPSCs), published this month in Nature.

They compared copy number variations (CNVs) of different passages of human iPSCs with the original fibroblast cells and human ES cells and found that early passage iPSCs contained a higher number of deletions than late passage iPSCs and the other cell types. These deletions are generated during the reprogramming process, and most are lost with subsequent passages due to strong negative selection pressure.

Several copy number changes were found to be located within genes and regions essential for maintaining an undifferentiated state. As well, deletions occurred more frequently in common fragile sites (CFSs) in reprogrammed iPSCs.

The findings demonstrate that the reprogramming process is associated with high mutation rates and give researchers new insights into the reprogramming process, and will help make future applications of stem cell creation and subsequent use safer.

Copy number variation and selection during reprogramming to pluripotency. Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Närvä E, Ng S, Sourour M, Hämäläinen R, Olsson C, Lundin K, Mikkola M, Trokovic R, Peitz M, Brüstle O, Bazett-Jones DP, Alitalo K, Lahesmaa R, Nagy A, Otonkoski T. Nature. 2011 Mar 3. [Abstract]


Dr. Husain Appointed new TGRI Director

Dr. Mansoor HusainCongratulations to the McEwen Centre's Dr. Mansoor Husain on being appointed the new Director of the Toronto General Research Institute. He will officially begin this role in May 2011.

As a specialist in cardiovascular disease and nuclear cardiology, Dr. Husain brings outstanding clinical and research credentials to the role. He is currently Director of Research at the Peter Munk Cardiac Centre at UHN and Director of the Heart & Stroke/Richard Lewar Centre of Excellence at the University of Toronto.


Dr. Shoichet Named to the Order of Ontario

Dr. Molly ShoichetCongratulations to Dr. Molly Shoichet, who has been appointed to the Province's highest honour, in recognition of her contribution to regenerative medicine--designing strategies and materials to help the body heal itself after traumatic injury, in particular to the brain and spinal cord.

The Order of Ontario is awarded to Ontarians for excellence and achievement in any field. About 25 people are invested into the Order of Ontario each year, and are considered an example of excellence to all Ontarians.


Upcoming Stem Cell and Regenerative Medicine Events

Mark Your CalendarsThe next Stem Cell Rounds, Hot Topics in Mesenchymal Stem Cells, will take place on Tuesday, March 29, 2011 at 4:30 pm in Room 6, Tanz Neuroscience Building. It will include lectures by Dr. Sevan Hopyan (Hopsital for Sick Children - HSC), Kristine McKenzie (Dr. Aubin's lab, UT), and Jason Rockel (Dr. Alman's lab, HSC).

The 4th Annual Regenerative Medicine Symposium will take place on April 6-7, 2011, hosted by the Training Program in Regenerative Medicine (TPRM) and its sponsors. This symposium will include keynote lectures from Drs. Peter Zandstra and Connie Eaves (UBC). For more information, visit the TPRM website.


Heart & Stroke Grant Results Announced

Heart & Stroke FoundationCongratulations to McEwen researchers for their success in the latest round of operating grants awarded by the Heart and Stroke Foundation of Ontario. Drs. Mansoor Husain and Peter Zandstra were awarded renewals of their grants.


March 2011 | mcewencentre.ca |

McEwen Centre for Regenerative Medicine

Recent Publications

A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury. Fehlings M, Theodore N, Harrop J, Maurais G, Kuntz C, Shaffrey CI, Kwon BK, Chapman JR, Yee A, Tighe A, McKerracher L. J Neurotrauma. 2011 Mar 8. [Abstract]

The potential of nanoscale combinations of self-assembling peptides and amino acids of the Src tyrosine kinase inhibitor in acute lung injury therapy. Fung SY, Oyaizu T, Yang H, Yuan Y, Han B, Keshavjee S, Liu M. Biomaterials. 2011 Mar 2. [Abstract]

Neural stem cells are increased after loss of ß-catenin, but neural progenitors undergo cell death. Holowacz T, Huelsken J, Dufort D, van der Kooy D. Eur J Neurosci. 2011 Mar 7. [Abstract]

Emerging approaches to the surgical management of acute traumatic spinal cord injury. Wilson JR, Fehlings MG. Neurotherapeutics. 2011 Mar 4. [Abstract]

Peptide-mediated disruption of calmodulin-cyclin E interactions inhibits proliferation of vascular smooth muscle cells and neointima formation. Hui S, Choi J, Zaidi S, Momen A, Steinbach SK, Sadi AM, Ban K, Husain M. Circ Res. 2011 Mar 3. [Abstract]

Copy number variation and selection during reprogramming to pluripotency. Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Närvä E, Ng S, Sourour M, Hämäläinen R, Olsson C, Lundin K, Mikkola M, Trokovic R, Peitz M, Brüstle O, Bazett-Jones DP, Alitalo K, Lahesmaa R, Nagy A, Otonkoski T. Nature. 2011 Mar 3. [Abstract]

The adult mouse and human pancreas contain rare multipotent stem cells that express insulin. Smukler SR, Arntfield ME, Razavi R, Bikopoulos G, Karpowicz P, Seaberg R, Dai F, Lee S, Ahrens R, Fraser PE, Wheeler MB, van der Kooy D. Cell Stem Cell. 2011 Mar 4. [Abstract]

Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells. Green MD, Chen A, Nostro MC, d'Souza SL, Schaniel C, Lemischka IR, Gouon-Evans V, Keller G, Snoeck HW. Nat Biotechnol. 2011 Feb 27. [Abstract]

A novel tissue-engineered approach to problems of the postpneumonectomy space. Tsunooka N, Hirayama S, Medin JA, Liles WC, Keshavjee S, Waddell TK. Ann Thorac Surg. 2011 Mar. [Abstract]

Utility of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of mediastinal masses of unknown etiology. Yasufuku K, Nakajima T, Fujiwara T, Yoshino I, Keshavjee S. Ann Thorac Surg. 2011 Mar. [Abstract]

Induced pluripotent stem cell lines derived from equine fibroblasts. Nagy K, Sung HK, Zhang P, Laflamme S, Vincent P, Agha-Mohammadi S, Woltjen K, Monetti C, Michael IP, Smith LC, Nagy A. Stem Cell Rev. 2011 Feb 24. [Abstract]

Cell-based transplantation strategies to promote plasticity following spinal cord injury. Ruff CA, Wilcox JT, Fehlings MG. Exp Neurol. 2011 Feb 17. [Abstract]

Diels-Alder click cross-linked hyaluronic acid hydrogels for tissue engineering. Nimmo CM, Owen SC, Shoichet MS. Biomacromolecules. 2011 Feb 11. [Abstract]