Correction of sickle cell disease by homologous recombination in embryonic stem cells

Wu, Li‐Chen; Sun, Chengzhen; Ryan, Thomas M.; Pawlik, Kevin M.; Ren, Jinxiang; Townes, Tim M.

doi:10.1182/blood-2006-02-004812

Cited by 270 publications

(298 citation statements)

References 33 publications

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“…Upon analysis, the engrafted mice showed mature lymphoid cells. In 2006, a similar experiment was performed with the Townes humanized SCA mouse model (Wu et al 2006). Autologous ESCs were genetically corrected by homologous recombination, differentiated toward the hematopoietic lineage, and transplanted into the Townes mice.…”

Section: Hemoglobinopathy Disease Models-in Vivo and In Vitromentioning

confidence: 99%

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Pluripotent Stem Cells in Research and Treatment of Hemoglobinopathies

Arora

Daley

2012

Cold Spring Harbor Perspectives in Medicine

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Section: Hemoglobinopathy Disease Models-in Vivo and In Vitromentioning

confidence: 99%

“…The Townes mouse is a knock-in model, in which both the mouse a-globin and b-globin genes were replaced with the human genes. The b-globin locus contains A g-globin and b S -globin (Wu et al 2006).…”

Section: Hemoglobinopathy Disease Models-in Vivo and In Vitromentioning

confidence: 99%

Pluripotent Stem Cells in Research and Treatment of Hemoglobinopathies

Arora

Daley

2012

Cold Spring Harbor Perspectives in Medicine

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“…84 Among the main obstacles are the instability of the vectors and the difficulty in integrating them into this type of cell. Other approaches, such as silencing the β S gene using interference RNA (iRNA), 85 or homologous recombination to substitute the β S gene with the β A gene, 86,87 are promising, but improvements are still needed to the gene transfer methods and efficacy must be demonstrated in animal models.…”

Section: S43mentioning

confidence: 99%

Genética das doenças hematológicas: as hemoglobinopatias hereditárias

Sonati¹,

Costa²

2008

J. Pediatr. (Rio J.)

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Objective: To summarize recently published data on the pathophysiology, diagnosis and treatment of sickle cell diseases and β-Thalassemias, the most relevant hereditary hemoglobinopathies in the global population.Sources: Searches were run on the MEDLINE and SCIELO databases, limited to the period from 2003 to May 2008, using the terms hereditary hemoglobinopathies, sickle cell diseases and β-thalassemia. Two books and two chapters were also included. Summary of the findings:More than 2,000 articles were identified; those providing the most important information and broadest views were selected.Conclusions: Morbidity and mortality rates from sickle cell diseases and β-thalassemia are still very high and represent an important challenge. Increased understanding of pathophysiological aspects has lead to significant improvements in treatment and prevention of these diseases. J Pediatr (Rio J). 2008;84(4 Suppl):S40-51:Hereditary hemoglobinopathies, sickle cell diseases, β-thalassemia.

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“…This allows for an unlimited supply of gene-corrected hematopoietic stem cells, which can be used for autologous transplantation. 82,83 In 2007, by using a humanized sickle cell knock-in mouse, Hanna et al 84 derived hematopoietic progenitors from mouse fibroblast iPS cells, which were able to reconstitute the hematopoietic system of sickle cell mice and correct their disease phenotype ( Figure 5). These mice demonstrated stable engraftment up to 12 weeks after transplant.…”

Section: Induced Pluripotent Stem Cells (Ips) Cellsmentioning

confidence: 99%

Allogeneic cellular and autologous stem cell therapy for sickle cell disease: ‘whom, when and how’

Freed

Talano

Small

et al. 2011

Bone Marrow Transplant

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Sickle cell disease (SCD) is an autosomal recessive inherited hematological disorder characterized by chronic hemolysis and vaso-occlusion, resulting in multiorgan dysfunction and premature death. The only known curative therapy for patients with severe SCD is myeloablative conditioning and allo-SCT from HLA-matched sibling donors. In this state of the art review, we discuss current and future considerations including patient selection/eligibility, intensity of conditioning regimens, allogeneic graft sources, graft manipulation, mixed donor chimerism, organ function and stability and autologous gene correction stem cell strategies. Recent novel approaches to promote mixed donor chimerism have included the use of matched unrelated adult donors, umbilical cord blood donors, haploidentical familial donors and the utilization of nonmyeloablative, such as reduced intensity and reduced toxicity conditioning regimens. Future strategies will include gene therapy and autologous gene correction stem cell designs. Prospects are bright for novel stem and cellular approaches for patients with severe SCD, and we are currently at the end of the beginning for utilizing cellular therapeutics for the curative treatment of this chronic and debilitating condition.

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Correction of sickle cell disease by homologous recombination in embryonic stem cells

Abstract: Previous studies have demonstrated that sickle cell disease (SCD) can be corrected in mouse models by transduction of hematopoietic stem cells with lentiviral vectors containing antisickling globin genes followed by transplantation of these cells into syngeneic recipients.

Cited by 270 publications

References 33 publications

Pluripotent Stem Cells in Research and Treatment of Hemoglobinopathies

Pluripotent Stem Cells in Research and Treatment of Hemoglobinopathies

Genética das doenças hematológicas: as hemoglobinopatias hereditárias

Allogeneic cellular and autologous stem cell therapy for sickle cell disease: ‘whom, when and how’

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