The use of simultaneous reprogramming and gene correction to generate an osteogenesis imperfecta patient COL1A1 c. 3936 G&gt;T iPSC line and an isogenic control iPSC line

Howden, Sara E.; Far, Hani Hosseini; Motazedian, Ali; Elefanty, Andrew G.; Stanley, Edouard G.; Lamandé, Shireen R.; Bateman, John F.

doi:10.1016/j.scr.2019.101453

Cited by 10 publications

(12 citation statements)

References 4 publications

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“…More recently human derived induced pluripotent stem cells (hiPSC) from OI patients or engineered iPSC to replicate OI have been generated. In combination with in vitro assays and in vivo models, these iPSC are being used to investigate therapeutic genome editing strategies and to test drug targets which may rescue the OI phenotype [165][166][167]. Notably, a proof-of-concept study demonstrated that MSC derived iPSC from OI patients, termed iMSC, could be genetically manipulated with adeno-associated virus mediated gene targeting to correct the mutant collagen genes.…”

Section: Bone Related Disease-osteogenesis Imperfectamentioning

confidence: 99%

Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

Arthur

Gronthos

2020

IJMS

159

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There has been an escalation in reports over the last decade examining the efficacy of bone marrow derived mesenchymal stem/stromal cells (BMSC) in bone tissue engineering and regenerative medicine-based applications. The multipotent differentiation potential, myelosupportive capacity, anti-inflammatory and immune-modulatory properties of BMSC underpins their versatile nature as therapeutic agents. This review addresses the current limitations and challenges of exogenous autologous and allogeneic BMSC based regenerative skeletal therapies in combination with bioactive molecules, cellular derivatives, genetic manipulation, biocompatible hydrogels, solid and composite scaffolds. The review highlights the current approaches and recent developments in utilizing endogenous BMSC activation or exogenous BMSC for the repair of long bone and vertebrae fractures due to osteoporosis or trauma. Current advances employing BMSC based therapies for bone regeneration of craniofacial defects is also discussed. Moreover, this review discusses the latest developments utilizing BMSC therapies in the preclinical and clinical settings, including the treatment of bone related diseases such as Osteogenesis Imperfecta.

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Section: Bone Related Disease-osteogenesis Imperfectamentioning

confidence: 99%

Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

Arthur

Gronthos

2020

IJMS

159

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“…In vivo delivery of Cas9-guide RNA complexes to repair abnormal genes has been successfully developed in murine models of autosomal dominantly inherited diseases [61]. In the case of OI, the CRISPR-Cas9 system was successfully used in mice, iPSCs lines and blood cells-derived iPSCs [62][63][64][65]. According to Peng et al, iPSCs corrected by the gene editing technology acquire the potential to repair pathological lesions and completely cure the disease [53].…”

Section: Methods Based On Genetic Engineering and Somatic Cells Reprogramming Into Ipscsmentioning

confidence: 99%

Osteogenesis Imperfecta: Current and Prospective Therapies

et al. 2021

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Osteogenesis Imperfecta (OI) is a group of connective tissue disorders with a broad range of phenotypes characterized primarily by bone fragility. The prevalence of OI ranges from about 1:15,000 to 1:20,000 births. Five types of the disease are commonly distinguished, ranging from a mild (type I) to a lethal one (type II). Types III and IV are severe forms allowing survival after the neonatal period, while type V is characterized by a mild to moderate phenotype with calcification of interosseous membranes. In most cases, there is a reduction in the production of normal type I collagen (col I) or the synthesis of abnormal collagen as a result of mutations in col I genes. Moreover, mutations in genes involved in col I synthesis and processing as well as in osteoblast differentiation have been reported. The currently available treatments try to prevent fractures, control symptoms and increase bone mass. Commonly used medications in OI treatment are bisphosphonates, Denosumab, synthetic parathyroid hormone and growth hormone for children therapy. The main disadvantages of these therapies are their relatively weak effectiveness, lack of effects in some patients or cytotoxic side effects. Experimental approaches, particularly those based on stem cell transplantation and genetic engineering, seem to be promising to improve the therapeutic effects of OI.

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“…Proof-of-principle for such functional testing has been described using CRISPR/Cas9 gene editing to engineer COL1A1 OI patient mutations into induced pluripotent stem cells. (34,35) While these cell lines represent valuable resources to study the mechanisms of specific mutations, such approaches remain expensive and poorly amenable for diagnostic testing of individual novel VUS.…”

Section: Identifying Gene Variants Associated With Bone Fragilitymentioning

confidence: 99%

Curative Cell and Gene Therapy for Osteogenesis Imperfecta

Lee

O’Donohue

Ginn

et al. 2020

Journal of Bone and Mineral Research

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Osteogenesis imperfecta (OI) describes a series of genetic bone fragility disorders that can have a substantive impact on patient quality of life. The multidisciplinary approach to management of children and adults with OI primarily involves the administration of antiresorptive medication, allied health (physiotherapy and occupational therapy), and orthopedic surgery. However, advances in gene editing technology and gene therapy vectors bring with them the promise of gene-targeted interventions to provide an enduring or perhaps permanent cure for OI. This review describes emergent technologies for cell-and gene-targeted therapies, major hurdles to their implementation, and the prospects of their future success with a focus on bone disorders.

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The use of simultaneous reprogramming and gene correction to generate an osteogenesis imperfecta patient COL1A1 c. 3936 G>T iPSC line and an isogenic control iPSC line

Cited by 10 publications

References 4 publications

Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

Osteogenesis Imperfecta: Current and Prospective Therapies

Curative Cell and Gene Therapy for Osteogenesis Imperfecta

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