De novo generation of HSCs from somatic and pluripotent stem cell sources

Vo, Linda T.; Daley, George Q.

doi:10.1182/blood-2014-10-570234

Cited by 98 publications

(97 citation statements)

References 94 publications

(65 reference statements)

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“…114,115 The major challenge is to develop efficient protocols to produce hematopoietic stem cells or other clinically relevant cellular outputs. 116 Irrespective of the target cell, a successful clinical gene editing approach must consider the fraction of the tissue that must be corrected to achieve therapeutic benefit. This may depend on the degree of selective advantage of effector cell relative to target cell (eg, survival advantage to be expected for erythrocytes and erythroid precursors deriving from corrected HSCs in hemoglobinopathy or for B-lymphocytes derived from corrected HSCs in X-linked agammaglobulinemia 117 ).…”

Section: Target Cellmentioning

confidence: 99%

A genome editing primer for the hematologist

Hoban

Bauer

2016

Blood

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Gene editing enables the site-specific modification of the genome. These technologies have rapidly advanced such that they have entered common use in experimental hematology to investigate genetic function. In addition, genome editing is becoming increasingly plausible as a treatment modality to rectify genetic blood disorders and improve cellular therapies. Genome modification typically ensues from site-specific double-strand breaks and may result in a myriad of outcomes. Even single-strand nicks and targeted biochemical modifications that do not permanently alter the DNA sequence (epigenome editing) may be powerful instruments. In this review, we examine the various technologies, describe their advantages and shortcomings for engendering useful genetic alterations, and consider future prospects for genome editing to impact hematology.

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Section: Target Cellmentioning

confidence: 99%

A genome editing primer for the hematologist

Hoban

Bauer

2016

Blood

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“…In addition to their therapeutic potential, iPSCs can also be used as in-vitro disease models 67 . Off-target nuclease binding activity 68 , efficient means of delivering the genome editing tools to target stem cell populations without loss of 'stemness' , genomic variation occurring with somatic reprogramming, efficient gene targeting by homology directed repair 69 , and developing functional HSCs from these genetically modified iPSC 70,71 are some of the challenges in the field.…”

Section: Recent Advances In Genetic Manipulation Technologymentioning

confidence: 99%

Gene therapy for hemoglobin disorders - a mini-review

Rai¹

2016

J Rare Dis Res Treat

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Gene therapy by either gene insertion or editing is an exciting curative therapeutic option for monogenic hemoglobin disorders like sickle cell disease and β-thalassemia. The safety and efficacy of gene transfer techniques has markedly improved with the use of lentivirus vectors. The clinical translation of this technology has met with good success, although key limitations include number of engraftable transduced hematopoietic stem cells and adequate transgene expression that results in complete correction of β0 thalassemia major. This highlights the need to identify and address factors that might be contributing to the in-vivo survival of the transduced hematopoietic stem cells or find means to improve expression from current vectors. In this review, we briefly discuss the gene therapy strategies specific to hemoglobinopathies, the success of the preclinical models and the current status of gene therapy clinical trials.

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“…Potential sources for future HCT constitute embryonic stem cells, induced pluripotent stem cells and, lately, directly reprogrammed cells [61]. These strategies however are currently at a very early experimental stage, and their clinical use critically depends on the development of robust differentiation protocols that generate sufficient HCT for long-term and multi-lineage reconstitution in due time.…”

Section: What Are Current Challenges In Hematopoietic Cell Transplantmentioning

confidence: 99%

Hematopoietic Stem Cells in Regenerative Medicine: Astray or on the Path?

Müller

Huppertz

Henschler

2016

Transfus Med Hemother

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Hematopoietic stem cells (HSCs) are the best characterized adult stem cells and the only stem cell type in routine clinical use. The concept of stem cell transplantation laid the foundations for the development of novel cell therapies within, and even outside, the hematopoietic system. Here, we report on the history of hematopoietic cell transplantation (HCT) and of HSC isolation, we briefly summarize the capabilities of HSCs to reconstitute the entire hemato/lymphoid cell system, and we assess current indications for HCT. We aim to draw the lines between areas where HCT has been firmly established, areas where HCT can in the future be expected to be of clinical benefit using their regenerative functions, and areas where doubts persist. We further review clinical trials for diverse approaches that are based on HCT. Finally, we highlight the advent of genome editing in HSCs and critically view the use of HSCs in non-hematopoietic tissue regeneration.

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De novo generation of HSCs from somatic and pluripotent stem cell sources

Cited by 98 publications

References 94 publications

A genome editing primer for the hematologist

A genome editing primer for the hematologist

Gene therapy for hemoglobin disorders - a mini-review

Hematopoietic Stem Cells in Regenerative Medicine: Astray or on the Path?

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