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Eisen, B.; Binah, O. DMD and Human Induced Pluripotent Stem Cells. Encyclopedia. Available online: https://encyclopedia.pub/entry/45232 (accessed on 27 July 2024).
Eisen B, Binah O. DMD and Human Induced Pluripotent Stem Cells. Encyclopedia. Available at: https://encyclopedia.pub/entry/45232. Accessed July 27, 2024.
Eisen, Binyamin, Ofer Binah. "DMD and Human Induced Pluripotent Stem Cells" Encyclopedia, https://encyclopedia.pub/entry/45232 (accessed July 27, 2024).
Eisen, B., & Binah, O. (2023, June 06). DMD and Human Induced Pluripotent Stem Cells. In Encyclopedia. https://encyclopedia.pub/entry/45232
Eisen, Binyamin and Ofer Binah. "DMD and Human Induced Pluripotent Stem Cells." Encyclopedia. Web. 06 June, 2023.
DMD and Human Induced Pluripotent Stem Cells
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This entry is adapted from the peer-reviewed paper 10.3390/ijms24108657

The development of somatic cell reprograming technology has enabled generation of human induced pluripotent stem cells (hiPSCs) which can be differentiated into different cell types. This technology provides a potentially endless pool of human cells for research. Furthermore, hiPSCs can be generated from patients, thus providing patient-specific cells and enabling research tailored to different mutations.

Duchenne muscular dystrophy DMD dystrophin gene

1. Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle degenerative disease caused by mutations in the dystrophin gene with an estimated prevalence between 1.3 and 2.1 per 10,000 live male births [1][2][3]. Dystrophin is the longest gene in the human DNA spanning 2.4 Mbp, with its 14 kb transcript consisting of 79 exons; it encodes the 427 kDa dystrophin protein [4][5]. Dystrophin is a major structural protein which is also involved in important metabolic processes [6][7][8]. In skeletal and cardiac muscle, dystrophin provides mechanical stability essential for contracting myocytes, and anchors the cellular cytoskeleton to the extracellular matrix (ECM) via the transmembrane dystrophin–glycoprotein complex (DGC) which links directly to extracellular laminin-2 [9][10][11]. Dystrophin can be grossly divided into three major domains: (1) the N-terminus and actin-binding domain (ABD) (exons 1–8), (2) the central rod segment consisting of 24 spectrin repeats (exons 9–63), and (3) the DGC-binding domain and C-terminus (exons 64–79) [12][13]. The majority of DMD mutations are deletions of one or more exons (60–65%), while duplications make up to 5–10% of the cases. The remaining (25–35%) are single-nucleotide variants, small deletions or insertions in the coding sequence, or splice site variants [14][15].
DMD symptoms start at an early age, usually around 2–3 years, when proximal muscles of the lower extremities begin to weaken. Gradually, the weakness progresses to the distal muscles and the upper limbs. With age, symptoms become more prominent, and by the early teens, patients are usually wheelchair-dependent. The cardiac involvement of DMD includes dilated cardiomyopathy (DCM) which is present in virtually all patients by their late teen years, along with conduction abnormalities, various arrhythmias and extensive fibrosis. Eventually, patients die by their late 20s or early 30s due to respiratory and cardiac failure [16][17][18].
The current gold-standard treatment of DMD includes glucocorticoids (GCs), usually from the age of 4 years, aimed at improving motor and pulmonary function, while also potentially delaying the onset of DCM [16][19][20]. Beyond known side-effects including weight gain, hirsutism and other Cushing’s syndrome symptoms, GCs do not change the disease outcome, but rather can only slow its course [19][21]. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are administered from around the age of 10 years to reduce mechanical stress on the heart [16][17]. Novel therapies include Eteplirsen, an exon 51 skipping drug, and Ataluren (PTC124), which promotes ribosomal readthrough of nonsense mutations [22][23]. However, these treatments are not intended for all DMD mutations, and there is a need for additional research and therapies to be developed.
The primary animal model used for DMD research is the mdx mouse, which carries a nonsense point mutation in exon 23 of the dystrophin gene [24][25]. Although mdx mice exhibit chronic degeneration of myofibers, they do not manifest some prominent symptoms of DMD. mdx mice display a slower disease progression compared to human DMD patients, and their relative lifespan is significantly longer. The slow progression of muscle pathology does not lead to extensive fibrosis as in humans, and the mice retain their mobility. Cardiac involvement follows a different course than in humans, as mdx mice initially develop hypertrophic cardiomyopathy (HCM), while human DMD patients suffer from contractile dysfunction and DCM [26][27][28]. It has been previously found that mdx mice heart mitochondria display an increase in Ca2+ uptake rate via activation of Ca2+ transport, possibly compensating for a defective sarcoplasmic reticulum (SR) [29][30][31]. This adaptiveness of mdx mice may be a key feature differentiating this model from human patients [32]. Indeed, these challenges led to the development of the D2.mdx model which exhibits a significantly more prominent disease phenotype [33]. An additional limitation of the mouse model lies in gender differences between female and male mdx mice. These differences include a more prominent cardiac involvement and skeletal muscle degeneration in female compared to male mice [34][35], contrary to slower disease progression in human female carriers [36].
Another important animal model was developed in rats by means of TALENs targeting DMD exon 23 [37]. mdx rats manifest progressive muscle degeneration accompanied by a reduction in muscle force, as well as dilated cardiomyopathy. Importantly, mdx rats display significant fibrosis in skeletal and cardiac muscle, similar to human patients but contrary to mdx mice [37][38]. However, some differences remain between mdx rats and human patients, as well as cells derived from human patients, including the lack of muscle calcifications [37], normal L-type Ca2+ current (ICa,L) [39][40][41], and unimpaired β-adrenergic cascade [39][42][43][44] in mdx rats.

2. Human Induced Pluripotent Stem Cells

In 2006 Takahashi and Yamanaka published their successful attempt to reprogram differentiated rat somatic cells into induced pluripotent stem cells (iPSCs) by means of the induction of four factors: Oct3/4, SOX2, c-Myc, and KLF4 [45]; in 2007, these breakthroughs were repeated in human somatic cells [46]. Human iPSCs (hiPSCs) present classic embryonic stem-cell (ESC) characteristics including trilineage differentiation capability [47][48]. Thus, provided proper culture and media conditions, hiPSCs can be differentiated into various cell types. Like ESCs, hiPSCs and hiPSC-derived cells can be used for disease modeling and drug testing [49][50][51][52][53]. Furthermore, hiPSCs can generate a potentially endless pool of differentiated cells from a minute biopsy of a single living human donor, whereas ESC generation requires the sacrifices of embryos [54]. This enables previously unmatched research capabilities of various human diseases without the limitations of different animal models. Indeed, in the past years, numerous papers utilized the reprogramming technique for disease modeling and regenerative medicine. Patient-specific hiPSCs served as a means for many discoveries and advancements in research of different diseases [51][52][55][56][57].
Due to the multitude of different mutations causing DMD [58], patient-specific hiPSCs provide a valuable approach to investigate the precise disease mechanisms resulting from these mutations. Furthermore, hiPSC research enables the potential development of new drugs and therapeutic approaches targeting specific mutations with higher efficacy than previous generic treatments. Importantly, investigating human-derived cells is preferable to using animal models which display different disease course and characteristics, compared to human patients.

References

  1. Moat, S.J.; Bradley, D.M.; Salmon, R.; Clarke, A.; Hartley, L. Newborn Bloodspot Screening for Duchenne Muscular Dystrophy: 21 Years Experience in Wales (UK). Eur. J. Hum. Genet. 2013, 21, 1049–1053.
  2. Romitti, P.A.; Zhu, Y.; Puzhankara, S.; James, K.A.; Nabukera, S.K.; Zamba, G.K.D.; Ciafaloni, E.; Cunniff, C.; Druschel, C.M.; Mathews, K.D.; et al. Prevalence of Duchenne and Becker Muscular Dystrophies in the United States. Pediatrics 2015, 135, 513–521.
  3. Ryder, S.; Leadley, R.M.; Armstrong, N.; Westwood, M.; de Kock, S.; Butt, T.; Jain, M.; Kleijnen, J. The Burden, Epidemiology, Costs and Treatment for Duchenne Muscular Dystrophy: An Evidence Review. Orphanet J. Rare Dis. 2017, 12, 79.
  4. Ahn, A.H.; Kunkel, L.M. The Structural and Functional Diversity of Dystrophin. Nat. Genet. 1993, 3, 283–291.
  5. Tennyson, C.N.; Klamut, H.J.; Worton, R.G. The Human Dystrophin Gene Requires 16 Hours to Be Transcribed and Is Cotranscriptionally Spliced. Nat. Genet. 1995, 9, 184–190.
  6. Brenman, J.E.; Chao, D.S.; Gee, S.H.; McGee, A.W.; Craven, S.E.; Santillano, D.R.; Wu, Z.; Huang, F.; Xia, H.; Peters, M.F.; et al. Interaction of Nitric Oxide Synthase with the Postsynaptic Density Protein PSD-95 and Al-pha1-Syntrophin Mediated by PDZ Domains. Cell 1996, 84, 757–767.
  7. Desguerre, I.; Mayer, M.; Leturcq, F.; Barbet, J.-P.; Gherardi, R.K.; Christov, C. Endomysial Fibrosis in Duchenne Muscular Dystrophy: A Marker of Poor Outcome Associated with Macrophage Alternative Activation. J. Neuropathol. Exp. Neurol. 2009, 68, 762–773.
  8. Millay, D.P.; Goonasekera, S.A.; Sargent, M.A.; Maillet, M.; Aronow, B.J.; Molkentin, J.D. Calcium Influx Is Sufficient to Induce Muscular Dystrophy through a TRPC-Dependent Mechanism. Proc. Natl. Acad. Sci. USA 2009, 106, 19023–19028.
  9. Xi, H.; Shin, W.S.; Suzuki, J.-I.; Nakajima, T.; Kawada, T.; Uehara, Y.; Nakazawa, M.; Toyo-oka, T. Dystrophin Disruption Might Be Related to Myocardial Cell Apoptosis Caused by Isoproterenol. J. Cardiovasc. Pharmacol. 2000, 36, S25-9.
  10. Brown, S.C.; Fassati, A.; Popplewell, L.; Page, A.M.; Henry, M.D.; Campbell, K.P.; Dickson, G. Dystrophic Phenotype Induced in Vitro by Antibody Blockade of Muscle Alpha-Dystroglycan-Laminin Interaction. J. Cell Sci. 1999, 112, 209–216.
  11. Sciandra, F.; Bozzi, M.; Bianchi, M.; Pavoni, E.; Giardina, B.; Brancaccio, A. Dystroglycan and Muscular Dystrophies Related to the Dystrophin-Glycoprotein Complex. Ann. Ist. Super. Sanita 2003, 39, 173–181.
  12. Kamdar, F.; Garry, D.J. Dystrophin-Deficient Cardiomyopathy. J. Am. Coll. Cardiol. 2016, 67, 2533–2546.
  13. Rybakova, I.N.; Patel, J.R.; Ervasti, J.M. The Dystrophin Complex Forms a Mechanically Strong Link between the Sarcolemma and Costameric Actin. J. Cell Biol. 2000, 150, 1209–1214.
  14. Takeshima, Y.; Yagi, M.; Okizuka, Y.; Awano, H.; Zhang, Z.; Yamauchi, Y.; Nishio, H.; Matsuo, M. Mutation Spectrum of the Dystrophin Gene in 442 Duchenne/Becker Muscular Dystrophy Cases from One Japanese Referral Center. J. Hum. Genet. 2010, 55, 379–388.
  15. Aartsma-Rus, A.; Van Deutekom, J.C.T.; Fokkema, I.F.; Van Ommen, G.-J.B.; Den Dunnen, J.T. Entries in the Lei-den Duchenne Muscular Dystrophy Mutation Database: An Overview of Mutation Types and Paradoxical Cases That Confirm the Reading-Frame Rule. Muscle Nerve 2006, 34, 135–144.
  16. Birnkrant, D.J.; Bushby, K.; Bann, C.M.; Apkon, S.D.; Blackwell, A.; Brumbaugh, D.; Case, L.E.; Clemens, P.R.; Hadjiyannakis, S.; Pandya, S.; et al. Diagnosis and Management of Duchenne Muscular Dystrophy, Part 1: Diagnosis, and Neuromuscular, Rehabilitation, Endocrine, and Gastrointestinal and Nutritional Management. Lancet Neurol. 2018, 17, 251–267.
  17. McNally, E.M.; Kaltman, J.R.; Benson, D.W.; Canter, C.E.; Cripe, L.H.; Duan, D.; Finder, J.D.; Groh, W.J.; Hoffman, E.P.; Judge, D.P.; et al. Contemporary Cardiac Issues in Duchenne Muscular Dystrophy. Working Group of the National Heart, Lung, and Blood Institute in Collaboration with Parent Project Muscular Dystrophy. Circulation 2015, 131, 1590–1598.
  18. Passamano, L.; Taglia, A.; Palladino, A.; Viggiano, E.; D’Ambrosio, P.; Scutifero, M.; Rosaria Cecio, M.; Torre, V.; DE Luca, F.; Picillo, E.; et al. Improvement of Survival in Duchenne Muscular Dystrophy: Retrospective Analysis of 835 Patients. Acta Myol. 2012, 31, 121–125.
  19. Gloss, D.; Moxley, R.T.; Ashwal, S.; Oskoui, M. Practice Guideline Update Summary: Corticosteroid Treatment of Duchenne Muscular Dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2016, 86, 465–472.
  20. Matthews, E.; Brassington, R.; Kuntzer, T.; Jichi, F.; Manzur, A.Y. Corticosteroids for the Treatment of Duchenne Muscular Dystrophy. Cochrane Database Syst. Rev. 2016, 5, CD003725.
  21. Griggs, R.C.; Moxley, R.T.; Mendell, J.R.; Fenichel, G.M.; Brooke, M.H.; Pestronk, A.; Miller, J.P. Prednisone in Duchenne Dystrophy. A Randomized, Controlled Trial Defining the Time Course and Dose Response. Clinical Investigation of Duchenne Dystrophy Group. Arch. Neurol. 1991, 48, 383–388.
  22. Mendell, J.R.; Goemans, N.; Lowes, L.P.; Alfano, L.N.; Berry, K.; Shao, J.; Kaye, E.M.; Mercuri, E.; Eteplirsen Study Group and Telethon Foundation DMD Italian Network. Longitudinal Effect of Eteplirsen versus Historical Control on Ambulation in Duchenne Muscular Dystrophy. Ann. Neurol. 2016, 79, 257–271.
  23. McDonald, C.M.; Campbell, C.; Torricelli, R.E.; Finkel, R.S.; Flanigan, K.M.; Goemans, N.; Heydemann, P.; Kaminska, A.; Kirschner, J.; Muntoni, F.; et al. Ataluren in Patients with Nonsense Mutation Duchenne Muscular Dystrophy (ACT DMD): A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. Lancet 2017, 390, 1489–1498.
  24. Bulfield, G.; Siller, W.G.; Wight, P.A.; Moore, K.J. X Chromosome-Linked Muscular Dystrophy (Mdx) in the Mouse. Proc. Natl. Acad. Sci. USA 1984, 81, 1189–1192.
  25. Ng, R.; Banks, G.B.; Hall, J.K.; Muir, L.A.; Ramos, J.N.; Wicki, J.; Odom, G.L.; Konieczny, P.; Seto, J.; Chamberlain, J.R.; et al. Animal Models of Muscular Dystrophy. Prog. Mol. Biol. Transl. Sci. 2012, 105, 83–111.
  26. Carnwath, J.W.; Shotton, D.M. Muscular Dystrophy in the Mdx Mouse: Histopathology of the Soleus and Extensor Digitorum Longus Muscles. J. Neurol. Sci. 1987, 80, 39–54.
  27. DiMario, J.X.; Uzman, A.; Strohman, R.C. Fiber Regeneration Is Not Persistent in Dystrophic (MDX) Mouse Skeletal Muscle. Dev. Biol. 1991, 148, 314–321.
  28. Quinlan, J.G.; Hahn, H.S.; Wong, B.L.; Lorenz, J.N.; Wenisch, A.S.; Levin, L.S. Evolution of the Mdx Mouse Cardiomyopathy: Physiological and Morphological Findings. Neuromuscul. Disord. 2004, 14, 491–496.
  29. Ascah, A.; Khairallah, M.; Daussin, F.; Bourcier-Lucas, C.; Godin, R.; Allen, B.G.; Petrof, B.J.; Des Rosiers, C.; Burelle, Y. Stress-Induced Opening of the Permeability Transition Pore in the Dystrophin-Deficient Heart Is Attenuated by Acute Treatment with Sildenafil. Am. J. Physiol. Heart Circ. Physiol. 2011, 300, 144–153.
  30. Jung, C.; Martins, A.S.; Niggli, E.; Shirokova, N. Dystrophic Cardiomyopathy: Amplification of Cellular Damage by Ca2+ Signalling and Reactive Oxygen Species-Generating Pathways. Cardiovasc. Res. 2008, 77, 766–773.
  31. Kyrychenko, V.; Poláková, E.; Janíček, R.; Shirokova, N. Mitochondrial Dysfunctions during Progression of Dystrophic Cardiomyopathy. Cell Calcium 2015, 58, 186–195.
  32. Garbincius, J.F.; Luongo, T.S.; Elrod, J.W. The Debate Continues—What Is the Role of MCU and Mitochondrial Calcium Uptake in the Heart? J. Mol. Cell Cardiol. 2020, 143, 163–174.
  33. Coley, W.D.; Bogdanik, L.; Vila, M.C.; Yu, Q.; Van Der Meulen, J.H.; Rayavarapu, S.; Novak, J.S.; Nearing, M.; Quinn, J.L.; Saunders, A.; et al. Effect of Genetic Background on the Dystrophic Phenotype in Mdx Mice. Hum. Mol. Genet. 2015, 25, 130–145.
  34. Bostick, B.; Yue, Y.; Duan, D. Gender Influences Cardiac Function in the Mdx Model of Duchenne Cardiomyopathy. Muscle Nerve 2010, 42, 600–603.
  35. Guéniot, L.; Latroche, C.; Thépenier, C.; Chatre, L.; Mazeraud, A.; Fiole, D.; Goossens, P.L.; Chrétien, F.; Jouvion, G. The Female Mdx Mouse: An Unexpected Vascular Story. J. Neurol. Neuromedicine 2016, 1, 41–53.
  36. Ishizaki, M.; Kobayashi, M.; Adachi, K.; Matsumura, T.; Kimura, E. Female Dystrophinopathy: Review of Current Literature. Neuromuscul. Disord. 2018, 28, 572–581.
  37. Larcher, T.; Lafoux, A.; Tesson, L.; Remy, S.V.; Thepenier, V.; François, V.; Guiner, C.L.; Goubin, H.; Dutilleul, M.V.; Guigand, L.; et al. Characterization of Dystrophin Deficient Rats: A New Model for Duchenne Muscular Dystrophy. PLoS ONE 2014, 9, e110371.
  38. Klingler, W.; Jurkat-Rott, K.; Lehmann-Horn, F.; Schleip, R. The Role of fibrosis in Duchenne Muscular Dystrophy. Acta Myologica 2012, 31, 184–195.
  39. Szabó, P.L.; Ebner, J.; Koenig, X.; Hamza, O.; Watzinger, S.; Trojanek, S.; Abraham, D.; Todt, H.; Kubista, H.; Schicker, K.; et al. Cardiovascular Phenotype of the Dmdmdx Rat—A Suitable Animal Model for Duchenne Muscular Dystrophy. Dis. Model. Mech. 2021, 14, 047704.
  40. Eisen, B.; Ben Jehuda, R.; Cuttitta, A.J.; Mekies, L.N.; Shemer, Y.; Baskin, P.; Reiter, I.; Willi, L.; Freimark, D.; Gherghiceanu, M.; et al. Electrophysiological Abnormalities in Induced Pluripotent Stem Cell-Derived Cardiomyocytes Generated from Duchenne Muscular Dystrophy Patients. J. Cell. Mol. Med. 2019, 23, 2125–2135.
  41. Lin, B.; Li, Y.; Han, L.; Kaplan, A.D.; Ao, Y.; Kalra, S.; Bett, G.C.L.; Rasmusson, R.L.; Denning, C.; Yang, L. Model-ing and Study of the Mechanism of Dilated Cardiomyopathy Using Induced Pluripotent Stem Cells Derived from Individuals with Duchenne Muscular Dystrophy. Dis. Model. Mech. 2015, 8, 457–466.
  42. Jelinkova, S.; Vilotic, A.; Pribyl, J.; Aimond, F.; Salykin, A.; Acimovic, I.; Pesl, M.; Caluori, G.; Klimovic, S.; Urban, T.; et al. DMD Pluripotent Stem Cell Derived Cardiac Cells Recapitulate in Vitro Human Cardiac Pathophysiology. Front. Bioeng. Biotechnol. 2020, 8, 535.
  43. Mekies, L.N.; Regev, D.; Eisen, B.; Fernandez-Gracia, J.; Baskin, P.; Ben Jehuda, R.; Shulman, R.; Reiter, I.; Palty, R.; Arad, M.; et al. Depressed β-Adrenergic Inotropic Responsiveness and Intracellular Calcium Handling Abnormalities in Duchenne Muscular Dystrophy Patients’ Induced Pluripotent Stem Cell–Derived Cardiomyocytes. J. Cell. Mol. Med. 2021, 25, 3922–3934.
  44. Kamdar, F.; Das, S.; Gong, W.; Klaassen Kamdar, A.; Meyers, T.A.; Shah, P.; Ervasti, J.M.; Townsend, D.W.; Kamp, T.J.; Wu, J.C.; et al. Stem Cell-Derived Cardiomyocytes and Beta-Adrenergic Receptor Blockade in Duchenne Muscular Dystrophy Cardiomyopathy. J. Am. Coll. Cardiol. 2020, 75, 1159–1174.
  45. Takahashi, K.; Yamanaka, S. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell 2006, 126, 663–676.
  46. Takahashi, K.; Tanabe, K.; Ohnuki, M.; Narita, M.; Ichisaka, T.; Tomoda, K.; Yamanaka, S. Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors. Cell 2007, 131, 861–872.
  47. Guenther, M.G.; Frampton, G.M.; Soldner, F.; Hockemeyer, D.; Mitalipova, M.; Jaenisch, R.; Young, R.A. Chroma-tin Structure and Gene Expression Programs of Human Embryonic and Induced Pluripotent Stem Cells. Cell Stem Cell 2010, 7, 249–257.
  48. Zhao, M.-T.; Chen, H.; Liu, Q.; Shao, N.-Y.; Sayed, N.; Wo, H.-T.; Zhang, J.Z.; Ong, S.-G.; Liu, C.; Kim, Y.; et al. Molecular and Functional Resemblance of Differentiated Cells Derived from Isogenic Human IPSCs and SCNT-Derived ESCs. Proc. Natl. Acad. Sci. USA 2017, 114, E11111–E11120.
  49. Soldner, F.; Hockemeyer, D.; Beard, C.; Gao, Q.; Bell, G.W.; Cook, E.G.; Hargus, G.; Blak, A.; Cooper, O.; Mitalipova, M.; et al. Parkinson’s Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Fac-tors. Cell 2009, 136, 964–977.
  50. Maehr, R.; Chen, S.; Snitow, M.; Ludwig, T.; Yagasaki, L.; Goland, R.; Leibel, R.L.; Melton, D.A. Generation of Pluripotent Stem Cells from Patients with Type 1 Diabetes. Proc. Natl. Acad. Sci. USA 2009, 106, 15768–15773.
  51. Ben Jehuda, R.; Eisen, B.; Shemer, Y.; Mekies, L.N.; Szantai, A.; Reiter, I.; Cui, H.; Guan, K.; Haron-Khun, S.; Freimark, D.; et al. CRISPR Correction of the PRKAG2 Gene Mutation in the Patient’s Induced Pluripotent Stem Cell-Derived Cardiomyocytes Eliminates Electrophysiological and Structural Abnormalities. Heart Rhythm. 2018, 15, 267–276.
  52. Hallas, T.; Eisen, B.; Shemer, Y.; Ben Jehuda, R.; Mekies, L.N.; Naor, S.; Schick, R.; Eliyahu, S.; Reiter, I.; Vlodavsky, E.; et al. Investigating the Cardiac Pathology of SCO2-Mediated Hypertrophic Cardiomyopathy Using Patients Induced Pluripotent Stem Cell-Derived Cardiomyocytes. J. Cell. Mol. Med. 2017, 22, 913–925.
  53. Eisen, B.; Ben Jehuda, R.; Cuttitta, A.J.; Mekies, L.N.; Reiter, I.; Ramchandren, S.; Arad, M.; Michele, D.E.; Binah, O. Generation of Duchenne Muscular Dystrophy Patient-Specific Induced Pluripotent Stem Cell Line Lacking Exons 45-50 of the Dystrophin Gene (IITi001-A). Stem Cell Res. 2018, 29, 111–114.
  54. Dimos, J.T.; Rodolfa, K.T.; Niakan, K.K.; Weisenthal, L.M.; Mitsumoto, H.; Chung, W.; Croft, G.F.; Saphier, G.; Leibel, R.; Goland, R.; et al. Induced Pluripotent Stem Cells Generated from Patients with ALS Can Be Differentiated into Motor Neurons. Science 2008, 321, 1218–1221.
  55. Carlson, C.; Koonce, C.; Aoyama, N.; Einhorn, S.; Fiene, S.; Thompson, A.; Swanson, B.; Anson, B.; Kattman, S. Phenotypic Screening with Human IPS Cell-Derived Cardiomyocytes: HTS-Compatible Assays for Interrogating Cardiac Hypertrophy. J. Biomol. Screen. 2013, 18, 1203–1211.
  56. Novak, A.; Barad, L.; Lorber, A.; Gherghiceanu, M.; Reiter, I.; Eisen, B.; Eldor, L.; Itskovitz-Eldor, J.; Eldar, M.; Arad, M.; et al. Functional Abnormalities in IPSC-Derived Cardiomyocytes Generated from CPVT1 and CPVT2 Patients Carrying Ryanodine or Calsequestrin Mutations. J. Cell. Mol. Med. 2015, 19, 2006–2018.
  57. Schick, R.; Mekies, L.N.; Shemer, Y.; Eisen, B.; Hallas, T.; Ben Jehuda, R.; Ben-Ari, M.; Szantai, A.; Willi, L.; Shul-man, R.; et al. Functional Abnormalities in Induced Pluripotent Stem Cell-Derived Cardiomyocytes Generated from Titin-Mutated Patients with Dilated Cardiomyopathy. PLoS ONE 2018, 13, e0205719.
  58. Flanigan, K.M.; Dunn, D.M.; von Niederhausern, A.; Soltanzadeh, P.; Gappmaier, E.; Howard, M.T.; Sampson, J.B.; Mendell, J.R.; Wall, C.; King, W.M.; et al. Mutational Spectrum of DMD Mutations in Dystrophinopathy Patients: Application of Modern Diagnostic Techniques to a Large Cohort. Hum. Mutat. 2009, 30, 1657–1666.
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