Induced pluripotent stem cells from a spinal muscular atrophy patient

By A. Ebert, Junying Yu, F. F. Rose, Virginia B. Mattis, C. Lorson, James A. Thomson, C. Svendsen. Nature, 2008

1,473 citations recorded by the source corpus.

Spinal muscular atrophy is one of the most common inherited forms of neurological disease leading to infant mortality. Patients have selective loss of lower motor neurons resulting in muscle weakness, paralysis and often death. Although patient fibroblasts have been used extensively to study spinal muscular atrophy, motor neurons have a unique anatomy and physiology which may underlie their vulnerability to the disease process. Here we report the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy. These cells expanded robustly in culture, maintained the disease genotype and generated motor neurons that showed selective deficits compared to those derived from the child’s unaffected mother. This is the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. As such, it represents a promising resource to study disease mechanisms, screen new drug compounds and develop new therapies.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bd243156c0ca603a6e1f898e8b306236c00b2833

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Citations in the corpus

Immune Influence on Adult Neural Stem Cell Regulation and Function (2009, positive): “iPSC lines have been created from patients with neurological diseases such as PD, amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA) (Dimos et al., 2008; Ebert et al., 2009; Soldner et al., 2009).”
Immunogenicity of induced pluripotent stem cells (2011, positive): “Recent groundbreaking discovery that somatic cells can be reprogrammed into the induced pluripotent stem cells (iPSCs) with defined factors has provided tremendous potential for developing human disease models (Dimos et al., 2008; Ebert et al., 2009; Takahashi and Yamanaka, 2006).”
Molecular mechanisms and potential therapeutical targets in Huntington's disease. (2010, methodology): “More recently, the induced-Pluripotent Stem (iPS) technology was used for the pathological modeling of Spinal Muscular Atrophy (SMA) (170), and efforts are currently underway to derive iPS cells from HD patients (150, 430).”
A model for neural development and treatment of Rett Syndrome using human induced pluripotent stem cells (2010, background): “Although iPSCs have been generated for several neurological diseases (Dimos et al., 2008; Ebert et al., 2009; Hotta et al., 2009; Lee et al., 2009; Park et al., 2008; Soldner et al., 2009), the demonstration Cell 143, 527–539, November 12, 2010 ª2010 Elsevier Inc. 527 of disease-specific…”
Induced pluripotency: history, mechanisms, and applications. (2010, background): “Moreover, three promising reports showed that iPSCs derived from patients suffering from the devastating disorders SMA (Ebert et al. 2009), familial dysautonomia (FD) (Lee et al.”
Modeling early retinal development with human embryonic and induced pluripotent stem cells (2009, background): “The potential for iPS cells to generate multiple retinal cell types will aid in the development of in vitro models of human retinal degenerative diseases and stimulate investigation into customized stem cell therapies for patients afflicted by these disorders (34, 35).”
Mechanisms Underlying Inflammation in Neurodegeneration (2010, neutral): “The recent demonstration that induced pluripotent stem (iPS) cells derived from ALS patients can be differentiated into astrocytes and specific types of neurons represents an important advance for developing in vitro humanized systems for mechanistic studies and evaluation of therapeutic agents (Dim”
Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency (2010, background): “These human iPSCs would overcome the drawbacks of using hESCs and allow for the direct examination of diseased cells for pathological studies and drug screening; this has recently been performed on iPSCs from patients of amyotrophic lateral sclerosis (13), spinal muscular atrophy (14), and familial ”
Somatic cell reprogramming and transitions between pluripotent states: facts, hypotheses, unresolved issues (2010, neutral): “This is important because for some iPSCs derived from patients, a disease-specific in vitro phenotype has been reported (Carvajal-Vergara et al., 2010; Ebert et al., 2009).”