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Iyer 2017b MiPschool Obergurgl

From Bioblast
Shilpa Iyer
Patient-specific stem cell models for mitochondrial diseases.

Link: MitoEAGLE

Iyer S, Grace HE, Patrick Galdun P, Lesnefsky EJ, Mayr JA, Sperl W, Karall D, Rao RR, West F (2017)

Event: MiPschool Obergurgl 2017


Mitochondrial DNA (mtDNA) mutations are associated with a wide range of human diseases; and more specifically are causative for classic mitochondrial disorders like Leigh’s Syndrome (LS). LS has no current cure and no adequate model for understanding the rapid fatality associated with the disease. Excess accumulation of mutant mtDNA molecules leads to failure of mitochondrial bioenergetics and causes fatalities. Other symptoms of LS usually include developmental, neural, cardiac and muscle impairments resulting in a chronic lack of energy in these patients. Reverse engineering adult cells into the early master stem cell state will now allow us to create disease-specific and patient-specific stem cells that can subsequently be differentiated into the many cells and tissues of the human body. Towards developing patient-specific stem cell model for LS, we have used a highly efficient mRNA nuclear reprogramming technology, for generating integration-free, virus-free, clinical grade human induced pluripotent stem cells (hiPSCs). Our experimental outcomes demonstrate successful reprogramming of a LS fibroblast (carrying 8993T>G) to a hiPSC state. The LS-hiPSC exhibited all hallmarks of a pluripotent stem cell, with the ability to differentiate into all three embryonic germ layers. More importantly, the LS-hiPSCs and differentiated derivatives continue to exhibit the 8993T>G mutation and continue to exhibit high levels of mutant mtDNA similar to the parental fibroblast. Generation and characterization of a stable LS-hiPSC line now opens up investigations to study the effects of mutant mtDNA load on altered bioenergetics.

Bioblast editor: Kandolf G O2k-Network Lab: AT Salzburg Sperl W, US AR Fayetteville Iyer S, US VA Richmond Lesnefsky EJ

Labels: MiParea: mtDNA;mt-genetics  Pathology: Other 

Tissue;cell: Fibroblast, Stem cells 

Event: D1, Oral 

Affiliations and support

Iyer S(1), Grace HE(2), Galdun P(3), Lesnefsky EJ(4), Mayr JA(5), Sperl W(5), Karall D(6), Rao RR(7), West F(2)
  1. Dept Biol Sciences, Fulbright College Arts Sciences, Univ of Arkansas, Fayetteville, Arkansas, USA.
  2. Regenerative Bioscience Center, Univ Georgia, Athens, GA, USA.
  3. Chem Life Science Engineering, Virginia Commonwealth Univ, Richmond, VA, USA
  4. Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA, USA
  5. Dept Pediatrics, Medical Univ of Salzburg, Austria.
  6. Dept Pediatrics, Medical Univ of Innsbruck, Austria.
  7. Dept Biomedical Engineering, College of Engineering, Univ of Arkansas, Fayetteville, AK USA. - [email protected]
Selected Mentor: Dr. Erich Gnaiger