Publications by authors named "Anne B C Cherry"

4 Publications

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A comparison of non-integrating reprogramming methods.

Nat Biotechnol 2015 Jan 1;33(1):58-63. Epub 2014 Dec 1.

1] Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Harvard Stem Cell Institute, Cambridge, Massachusetts, USA. [3] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA. [4] Howard Hughes Medical Institute, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts, USA.

Human induced pluripotent stem cells (hiPSCs) are useful in disease modeling and drug discovery, and they promise to provide a new generation of cell-based therapeutics. To date there has been no systematic evaluation of the most widely used techniques for generating integration-free hiPSCs. Here we compare Sendai-viral (SeV), episomal (Epi) and mRNA transfection mRNA methods using a number of criteria. All methods generated high-quality hiPSCs, but significant differences existed in aneuploidy rates, reprogramming efficiency, reliability and workload. We discuss the advantages and shortcomings of each approach, and present and review the results of a survey of a large number of human reprogramming laboratories on their independent experiences and preferences. Our analysis provides a valuable resource to inform the use of specific reprogramming methods for different laboratories and different applications, including clinical translation.
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http://dx.doi.org/10.1038/nbt.3070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329913PMC
January 2015

Induced pluripotent stem cells with a mitochondrial DNA deletion.

Stem Cells 2013 Jul;31(7):1287-97

Boston Children's Hospital, Boston, MA, USA.

In congenital mitochondrial DNA (mtDNA) disorders, a mixture of normal and mutated mtDNA (termed heteroplasmy) exists at varying levels in different tissues, which determines the severity and phenotypic expression of disease. Pearson marrow pancreas syndrome (PS) is a congenital bone marrow failure disorder caused by heteroplasmic deletions in mtDNA. The cause of the hematopoietic failure in PS is unknown, and adequate cellular and animal models are lacking. Induced pluripotent stem (iPS) cells are particularly amenable for studying mtDNA disorders, as cytoplasmic genetic material is retained during direct reprogramming. Here, we derive and characterize iPS cells from a patient with PS. Taking advantage of the tendency for heteroplasmy to change with cell passage, we isolated isogenic PS-iPS cells without detectable levels of deleted mtDNA. We found that PS-iPS cells carrying a high burden of deleted mtDNA displayed differences in growth, mitochondrial function, and hematopoietic phenotype when differentiated in vitro, compared to isogenic iPS cells without deleted mtDNA. Our results demonstrate that reprogramming somatic cells from patients with mtDNA disorders can yield pluripotent stem cells with varying burdens of heteroplasmy that might be useful in the study and treatment of mitochondrial diseases.
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http://dx.doi.org/10.1002/stem.1354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3692613PMC
July 2013

Reprogrammed cells for disease modeling and regenerative medicine.

Annu Rev Med 2013 ;64:277-90

Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Boston, MA, USA.

The conversion of somatic cells into pluripotent cells is transforming the way diseases are researched and treated. Induced pluripotent stem (iPS) cells' promise may soon be realized in the field of hematology, as hematopoietic stem cell transplants are already commonplace in clinics around the world. We provide a current comparison between induced pluripotent and embryonic stem cells, describe progress toward modeling hematological disorders using iPS cells, and illustrate the hurdles that must be overcome before iPS cell therapies will be available in clinics.
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http://dx.doi.org/10.1146/annurev-med-050311-163324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629705PMC
July 2013

Reprogramming cellular identity for regenerative medicine.

Cell 2012 Mar;148(6):1110-22

Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, MA 02115, USA.

Although development leads unidirectionally toward more restricted cell fates, recent work in cellular reprogramming has proven that one cellular identity can strikingly convert into another, promising countless applications in biomedical research and paving the way for modeling diseases with patient-derived stem cells. To date, there has been little discussion of which disease models are likely to be most informative. Here, we review evidence demonstrating that, because environmental influences and epigenetic signatures are largely erased during reprogramming, patient-specific models of diseases with strong genetic bases and high penetrance are likely to prove most informative in the near term. We also discuss the implications of the new reprogramming paradigm in biomedicine and outline how reprogramming of cell identities is enhancing our understanding of cell differentiation and prospects for cellular therapies and in vivo regeneration.
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http://dx.doi.org/10.1016/j.cell.2012.02.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3354575PMC
March 2012