Skip to main content

Advertisement

SpringerLink
Log in

Spinal Muscular Atrophy Modeling and Treatment Advances by Induced Pluripotent Stem Cells Studies

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Spinal Muscular Atrophy (SMA) is a neurodegenerative disease characterized by specific and predominantly lower motor neuron (MN) loss. SMA is the main reason for infant death, while about one in 40 children born is a healthy carrier. SMA is caused by decreased levels of production of a ubiquitously expressed gene: the survival motor neuron (SMN). All SMA patients present mutations of the telomeric SMN1 gene, but many copies of a centromeric, partially functional paralog gene, SMN2, can somewhat compensate for the SMN1 deficiency, scaling inversely with phenotypic harshness. Because the study of neural tissue in and from patients presents too many challenges and is very often not feasible; the use of animal models, such as the mouse, had a pivotal impact in our understanding of SMA pathology but could not portray totally satisfactorily the elaborate regulatory mechanisms that are present in higher animals, particularly in humans. And while recent therapeutic achievements have been substantial, especially for very young infants, some issues should be considered for the treatment of older patients. An alternative way to study SMA, and other neurological pathologies, is the use of induced pluripotent stem cells (iPSCs) derived from patients. In this work, we will present a wide analysis of the uses of iPSCs in SMA pathology, starting from basic science to their possible roles as therapeutic tools.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663–676.

    CAS  PubMed  Google Scholar 

  2. Dubowitz, V. (1974). Benign infantile spinal muscular atrophy. Developmental Medicine and Child Neurology, 16(5), 672–675.

    CAS  PubMed  Google Scholar 

  3. Dubowitz, V. (1999). Very severe spinal muscular atrophy (SMA type 0): an expanding clinical phenotype. European Journal of Paediatric Neurology, 3(2), 49–51.

    CAS  PubMed  Google Scholar 

  4. Pearn, J. H., Hudgson, P., & Walton, J. N. (1978). A clinical and genetic study of spinal muscular atrophy of adult onset: the autosomal recessive form as a discrete disease entity. Brain, 101(4), 591–606.

    CAS  PubMed  Google Scholar 

  5. Bottai, D., & Adami, R. (2013). Spinal muscular atrophy: new findings for an old pathology. Brain Pathology, 23(6), 613–622.

    PubMed  PubMed Central  Google Scholar 

  6. Werdnig, G. (1891). Zwei frühinfantile hereditäre Fälle von progressiver Muskelatrophie unter dem Bilde der Dystrophie, aber anf neurotischer Grundlage. Archiv für Psychiatrie und Nervenkrankheiten, 22(2), 437–480.

    Google Scholar 

  7. Werdnig, G. (1971). Two early infantile hereditary cases of progressive muscular atrophy simulating dystrophy, but on a neural basis. 1891. Archives of Neurology, 25(3), 276–278.

    CAS  PubMed  Google Scholar 

  8. Sugarman, E. A., Nagan, N., Zhu, H., Akmaev, V. R., Zhou, Z., Rohlfs, E. M., Flynn, K., Hendrickson, B. C., Scholl, T., Sirko-Osadsa, D. A., & Allitto, B. A. (2012). Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72 400 specimens. European Journal of Human Genetics, 20(1), 27–32.

    PubMed  Google Scholar 

  9. Prior, T. W., & Russman, B. S. (1993). Spinal Muscular Atrophy. Seattle (WA): University of Washington.

    Google Scholar 

  10. Rudnik-Schoneborn, S., Forkert, R., Hahnen, E., Wirth, B., & Zerres, K. (1996). Clinical spectrum and diagnostic criteria of infantile spinal muscular atrophy: further delineation on the basis of SMN gene deletion findings. Neuropediatrics, 27(1), 8–15.

    CAS  PubMed  Google Scholar 

  11. Rudnik-Schoneborn, S., Hausmanowa-Petrusewicz, I., Borkowska, J., & Zerres, K. (2001). The predictive value of achieved motor milestones assessed in 441 patients with infantile spinal muscular atrophy types II and III. European Neurology, 45(3), 174–181.

    CAS  PubMed  Google Scholar 

  12. Mercuri, E., Bertini, E., & Iannaccone, S. T. (2012). Childhood spinal muscular atrophy: controversies and challenges. Lancet Neurology, 11(5), 443–452.

    PubMed  Google Scholar 

  13. Finkel, R. S., McDermott, M. P., Kaufmann, P., Darras, B. T., Chung, W. K., Sproule, D. M., Kang, P. B., Foley, A. R., Yang, M. L., Martens, W. B., Oskoui, M., Glanzman, A. M., Flickinger, J., Montes, J., Dunaway, S., O'Hagen, J., Quigley, J., Riley, S., Benton, M., Ryan, P. A., Montgomery, M., Marra, J., Gooch, C., & De Vivo, D. C. (2014). Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology, 83(9), 810–817.

    PubMed  PubMed Central  Google Scholar 

  14. Talbot, K., & Tizzano, E. F. (2017). The clinical landscape for SMA in a new therapeutic era. Gene Therapy, 24(9), 529–533.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Brzustowicz, L. M., Lehner, T., Castilla, L. H., Penchaszadeh, G. K., Wilhelmsen, K. C., Daniels, R., Davies, K. E., Leppert, M., Ziter, F., Wood, D., et al. (1990). Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2–13.3. Nature, 344(6266), 540–541.

    CAS  PubMed  Google Scholar 

  16. Gilliam, T. C., Brzustowicz, L. M., Castilla, L. H., Lehner, T., Penchaszadeh, G. K., Daniels, R. J., Byth, B. C., Knowles, J., Hislop, J. E., Shapira, Y., et al. (1990). Genetic homogeneity between acute and chronic forms of spinal muscular atrophy. Nature, 345(6278), 823–825.

    CAS  PubMed  Google Scholar 

  17. Melki, J., Abdelhak, S., Sheth, P., Bachelot, M. F., Burlet, P., Marcadet, A., Aicardi, J., Barois, A., Carriere, J. P., Fardeau, M., et al. (1990). Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q. Nature, 344(6268), 767–768.

    CAS  PubMed  Google Scholar 

  18. Munsat, T. L., Skerry, L., Korf, B., Pober, B., Schapira, Y., Gascon, G. G., al-Rajeh, S. M., Dubowitz, V., Davies, K., Brzustowicz, L. M., et al. (1990). Phenotypic heterogeneity of spinal muscular atrophy mapping to chromosome 5q11.2–13.3 (SMA 5q). Neurology, 40(12), 1831–1836.

    CAS  PubMed  Google Scholar 

  19. Cobben, J. M., Scheffer, H., De Visser, M., Osinga, J., Frants, R., van der Steege, G., Wijmenga, C., ten Kate, L. P., van Ommen, G. J., & Buys, C. H. (1993). Linkage and apparent heterogeneity in proximal spinal muscular atrophies. Neuromuscular Disorders, 3(4), 327–333.

    CAS  PubMed  Google Scholar 

  20. Brzustowicz, L. M., Kleyn, P. W., Boyce, F. M., Lien, L. L., Monaco, A. P., Penchaszadeh, G. K., Das, K., Wang, C. H., Munsat, T. L., Ott, J., et al. (1992). Fine-mapping of the spinal muscular atrophy locus to a region flanked by MAP1B and D5S6. Genomics, 13(4), 991–998.

    CAS  PubMed  Google Scholar 

  21. Wirth, B., Pick, E., Leutner, A., Dadze, A., Voosen, B., Knapp, M., Piechaczek-Wappenschmidt, B., Rudnik-Schoneborn, S., Schonling, J., Cox, S., et al. (1994). Large linkage analysis in 100 families with autosomal recessive spinal muscular atrophy (SMA) and 11 CEPH families using 15 polymorphic loci in the region 5q11.2-q13.3. Genomics, 20(1), 84–93.

    CAS  PubMed  Google Scholar 

  22. Bussaglia, E., Clermont, O., Tizzano, E., Lefebvre, S., Burglen, L., Cruaud, C., Urtizberea, J. A., Colomer, J., Munnich, A., Baiget, M., et al. (1995). A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients. Nature Genetics, 11(3), 335–337.

    CAS  PubMed  Google Scholar 

  23. Clermont, O., Burlet, P., Lefebvre, S., Burglen, L., Munnich, A., & Melki, J. (1995). SMN gene deletions in adult-onset spinal muscular atrophy. Lancet, 346(8991–8992), 1712–1713.

    CAS  PubMed  Google Scholar 

  24. Cobben, J. M., van der Steege, G., Grootscholten, P., de Visser, M., Scheffer, H., & Buys, C. H. (1995). Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy. American Journal of Human Genetics, 57(4), 805–808.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Lefebvre, S., Burglen, L., Reboullet, S., Clermont, O., Burlet, P., Viollet, L., Benichou, B., Cruaud, C., Millasseau, P., Zeviani, M., et al. (1995). Identification and characterization of a spinal muscular atrophy-determining gene. Cell, 80(1), 155–165.

    CAS  PubMed  Google Scholar 

  26. McAndrew, P. E., Parsons, D. W., Simard, L. R., Rochette, C., Ray, P. N., Mendell, J. R., Prior, T. W., & Burghes, A. H. (1997). Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number. American Journal of Human Genetics, 60(6), 1411–1422.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Schwartz, M., Sorensen, N., Hansen, F. J., Hertz, J. M., Norby, S., Tranebjaerg, L., & Skovby, F. (1997). Quantification, by solid-phase minisequencing, of the telomeric and centromeric copies of the survival motor neuron gene in families with spinal muscular atrophy. Human Molecular Genetics, 6(1), 99–104.

    CAS  PubMed  Google Scholar 

  28. Lefebvre, S., Burlet, P., Liu, Q., Bertrandy, S., Clermont, O., Munnich, A., Dreyfuss, G., & Melki, J. (1997). Correlation between severity and SMN protein level in spinal muscular atrophy. Nature Genetics, 16(3), 265–269.

    CAS  PubMed  Google Scholar 

  29. Calucho, M., Bernal, S., Alias, L., March, F., Vencesla, A., Rodriguez-Alvarez, F. J., Aller, E., Fernandez, R. M., Borrego, S., Millan, J. M., Hernandez-Chico, C., Cusco, I., Fuentes-Prior, P., & Tizzano, E. F. (2018). Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases. Neuromuscular Disorders, 28(3), 208–215.

    PubMed  Google Scholar 

  30. Monani, U. R., Lorson, C. L., Parsons, D. W., Prior, T. W., Androphy, E. J., Burghes, A. H., & McPherson, J. D. (1999). A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Human Molecular Genetics, 8(7), 1177–1183.

    CAS  PubMed  Google Scholar 

  31. Murray, L. M., Talbot, K., & Gillingwater, T. H. (2010). Review: neuromuscular synaptic vulnerability in motor neurone disease: amyotrophic lateral sclerosis and spinal muscular atrophy. Neuropathology and Applied Neurobiology, 36(2), 133–156.

    CAS  PubMed  Google Scholar 

  32. Lorson, C. L., & Androphy, E. J. (2000). An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN. Human Molecular Genetics, 9(2), 259–265.

    CAS  PubMed  Google Scholar 

  33. Germain-Desprez, D., Brun, T., Rochette, C., Semionov, A., Rouget, R., & Simard, L. R. (2001). The SMN genes are subject to transcriptional regulation during cellular differentiation. Gene, 279(2), 109–117.

    CAS  PubMed  Google Scholar 

  34. La Bella, V., Cisterni, C., Salaun, D., & Pettmann, B. (1998). Survival motor neuron (SMN) protein in rat is expressed as different molecular forms and is developmentally regulated. The European Journal of Neuroscience, 10(9), 2913–2923.

    PubMed  Google Scholar 

  35. La Bella, V., Kallenbach, S., & Pettmann, B. (2000). Expression and subcellular localization of two isoforms of the survival motor neuron protein in different cell types. Journal of Neuroscience Research, 62(3), 346–356.

    PubMed  Google Scholar 

  36. Burlet, P., Huber, C., Bertrandy, S., Ludosky, M. A., Zwaenepoel, I., Clermont, O., Roume, J., Delezoide, A. L., Cartaud, J., Munnich, A., & Lefebvre, S. (1998). The distribution of SMN protein complex in human fetal tissues and its alteration in spinal muscular atrophy. Human Molecular Genetics, 7(12), 1927–1933.

    CAS  PubMed  Google Scholar 

  37. Gavrilov, D. K., Shi, X., Das, K., Gilliam, T. C., & Wang, C. H. (1998). Differential SMN2 expression associated with SMA severity. Nature Genetics, 20(3), 230–231.

    CAS  PubMed  Google Scholar 

  38. Glascock, J., Lenz, M., Hobby, K., & Jarecki, J. (2017). Cure SMA and our patient community celebrate the first approved drug for SMA. Gene Therapy, 24(9), 498–500.

    CAS  PubMed  Google Scholar 

  39. Paton, D. M. (2017). Nusinersen: antisense oligonucleotide to increase SMN protein production in spinal muscular atrophy. Drugs Today (Barc), 53(6), 327–337.

    CAS  Google Scholar 

  40. Singh, N. N., Howell, M. D., Androphy, E. J., & Singh, R. N. (2017). How the discovery of ISS-N1 led to the first medical therapy for spinal muscular atrophy. Gene Therapy, 24(9), 520–526.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Mercuri, E., Darras, B. T., Chiriboga, C. A., Day, J. W., Campbell, C., Connolly, A. M., Iannaccone, S. T., Kirschner, J., Kuntz, N. L., Saito, K., Shieh, P. B., Tulinius, M., Mazzone, E. S., Montes, J., Bishop, K. M., Yang, Q., Foster, R., Gheuens, S., Bennett, C. F., Farwell, W., Schneider, E., De Vivo, D. C., Finkel, R. S., & Group C S. (2018). Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy. The New England Journal of Medicine, 378(7), 625–635.

    CAS  PubMed  Google Scholar 

  42. Wurster, C. D., Winter, B., Wollinsky, K., Ludolph, A. C., Uzelac, Z., Witzel, S., Schocke, M., Schneider, R., & Kocak, T. (2019). Intrathecal administration of nusinersen in adolescent and adult SMA type 2 and 3 patients. Journal of Neurology, 266(1), 183–194.

    PubMed  Google Scholar 

  43. Mendell, J. R., Al-Zaidy, S., Shell, R., Arnold, W. D., Rodino-Klapac, L. R., Prior, T. W., Lowes, L., Alfano, L., Berry, K., Church, K., Kissel, J. T., Nagendran, S., L'Italien, J., Sproule, D. M., Wells, C., Cardenas, J. A., Heitzer, M. D., Kaspar, A., Corcoran, S., Braun, L., Likhite, S., Miranda, C., Meyer, K., Foust, K. D., Burghes, A. H. M., & Kaspar, B. K. (2017). Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. The New England Journal of Medicine, 377(18), 1713–1722.

    CAS  PubMed  Google Scholar 

  44. Prior, T. W., Krainer, A. R., Hua, Y., Swoboda, K. J., Snyder, P. C., Bridgeman, S. J., Burghes, A. H., & Kissel, J. T. (2009). A positive modifier of spinal muscular atrophy in the SMN2 gene. American Journal of Human Genetics, 85(3), 408–413.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Novelli, G., Calza, L., Amicucci, P., Giardino, L., Pozza, M., Silani, V., Pizzuti, A., Gennarelli, M., Piombo, G., Capon, F., & Dallapiccola, B. (1997). Expression study of survival motor neuron gene in human fetal tissues. Biochemical and Molecular Medicine, 61(1), 102–106.

    CAS  PubMed  Google Scholar 

  46. Schrank, B., Gotz, R., Gunnersen, J. M., Ure, J. M., Toyka, K. V., Smith, A. G., & Sendtner, M. (1997). Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proceedings of the National Academy of Sciences of the United States of America, 94(18), 9920–9925.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Lorson, C. L., & Androphy, E. J. (1998). The domain encoded by exon 2 of the survival motor neuron protein mediates nucleic acid binding. Human Molecular Genetics, 7(8), 1269–1275.

    CAS  PubMed  Google Scholar 

  48. Bertrandy, S., Burlet, P., Clermont, O., Huber, C., Fondrat, C., Thierry-Mieg, D., Munnich, A., & Lefebvre, S. (1999). The RNA-binding properties of SMN: deletion analysis of the zebrafish orthologue defines domains conserved in evolution. Human Molecular Genetics, 8(5), 775–782.

    CAS  PubMed  Google Scholar 

  49. Young, P. J., Man, N. T., Lorson, C. L., Le, T. T., Androphy, E. J., Burghes, A. H., & Morris, G. E. (2000). The exon 2b region of the spinal muscular atrophy protein, SMN, is involved in self-association and SIP1 binding. Human Molecular Genetics, 9(19), 2869–2877.

    CAS  PubMed  Google Scholar 

  50. Young, P. J., Day, P. M., Zhou, J., Androphy, E. J., Morris, G. E., & Lorson, C. L. (2002). A direct interaction between the survival motor neuron protein and p53 and its relationship to spinal muscular atrophy. The Journal of Biological Chemistry, 277(4), 2852–2859.

    CAS  PubMed  Google Scholar 

  51. Parsons, D. W., McAndrew, P. E., Monani, U. R., Mendell, J. R., Burghes, A. H., & Prior, T. W. (1996). An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene. Human Molecular Genetics, 5(11), 1727–1732.

    CAS  PubMed  Google Scholar 

  52. Xu, C. C., Denton, K. R., Wang, Z. B., Zhang, X., & Li, X. J. (2016). Abnormal mitochondrial transport and morphology as early pathological changes in human models of spinal muscular atrophy. Disease Models & Mechanisms, 9(1), 39–49.

    CAS  Google Scholar 

  53. Bowerman, M., Becker, C. G., Yanez-Munoz, R. J., Ning, K., Wood, M. J. A., Gillingwater, T. H., Talbot, K., & Consortium, U. S. R. (2017). Therapeutic strategies for spinal muscular atrophy: SMN and beyond. Disease Models & Mechanisms, 10(8), 943–954.

    CAS  Google Scholar 

  54. Chari, A., Paknia, E., & Fischer, U. (2009). The role of RNP biogenesis in spinal muscular atrophy. Current Opinion in Cell Biology, 21(3), 387–393.

    CAS  PubMed  Google Scholar 

  55. Neuenkirchen, N., Englbrecht, C., Ohmer, J., Ziegenhals, T., Chari, A., & Fischer, U. (2015). Reconstitution of the human U snRNP assembly machinery reveals stepwise Sm protein organization. The EMBO Journal, 34(14), 1925–1941.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Burghes, A. H., & Beattie, C. E. (2009). Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick? Nature Reviews. Neuroscience, 10(8), 597–609.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Meister, G., Buhler, D., Laggerbauer, B., Zobawa, M., Lottspeich, F., & Fischer, U. (2000). Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins. Human Molecular Genetics, 9(13), 1977–1986.

    CAS  PubMed  Google Scholar 

  58. Meister, G., Eggert, C., & Fischer, U. (2002). SMN-mediated assembly of RNPs: a complex story. Trends in Cell Biology, 12(10), 472–478.

    CAS  PubMed  Google Scholar 

  59. Malatesta, M., Scassellati, C., Meister, G., Plottner, O., Buhler, D., Sowa, G., Martin, T. E., Keidel, E., Fischer, U., & Fakan, S. (2004). Ultrastructural characterisation of a nuclear domain highly enriched in survival of motor neuron (SMN) protein. Experimental Cell Research, 292(2), 312–321.

    CAS  PubMed  Google Scholar 

  60. Patel, A. A., McCarthy, M., & Steitz, J. A. (2002). The splicing of U12-type introns can be a rate-limiting step in gene expression. The EMBO Journal, 21(14), 3804–3815.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Boulisfane, N., Choleza, M., Rage, F., Neel, H., Soret, J., & Bordonne, R. (2011). Impaired minor tri-snRNP assembly generates differential splicing defects of U12-type introns in lymphoblasts derived from a type I SMA patient. Human Molecular Genetics, 20(4), 641–648.

    CAS  PubMed  Google Scholar 

  62. Rage, F., Boulisfane, N., Rihan, K., Neel, H., Gostan, T., Bertrand, E., Bordonne, R., & Soret, J. (2013). Genome-wide identification of mRNAs associated with the protein SMN whose depletion decreases their axonal localization. RNA, 19(12), 1755–1766.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Lotti, F., Imlach, W. L., Saieva, L., Beck, E. S., Hao le, T., Li, D. K., Jiao, W., Mentis, G. Z., Beattie, C. E., McCabe, B. D., & Pellizzoni, L. (2012). An SMN-Dependent U12 Splicing Event Essential for Motor Circuit Function. Cell, 151(2), 440–454.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Hosseinibarkooie, S., Schneider, S., & Wirth, B. (2017). Advances in understanding the role of disease-associated proteins in spinal muscular atrophy. Expert Review of Proteomics, 14(7), 581–592.

    CAS  PubMed  Google Scholar 

  65. Burge, C. B., Padgett, R. A., & Sharp, P. A. (1998). Evolutionary fates and origins of U12-type introns. Molecular Cell, 2(6), 773–785.

    CAS  PubMed  Google Scholar 

  66. Levine, A., & Durbin, R. (2001). A computational scan for U12-dependent introns in the human genome sequence. Nucleic Acids Research, 29(19), 4006–4013.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Rochette, C. F., Gilbert, N., & Simard, L. R. (2001). SMN gene duplication and the emergence of the SMN2 gene occurred in distinct hominids: SMN2 is unique to Homo sapiens. Human Genetics, 108(3), 255–266.

    CAS  PubMed  Google Scholar 

  68. Liu, L. (2017). Linking Telomere Regulation to Stem Cell Pluripotency. Trends in Genetics, 33(1), 16–33.

    PubMed  Google Scholar 

  69. De Coppi, P., Bartsch, G., Jr., Siddiqui, M. M., Xu, T., Santos, C. C., Perin, L., Mostoslavsky, G., Serre, A. C., Snyder, E. Y., Yoo, J. J., Furth, M. E., Soker, S., & Atala, A. (2007). Isolation of amniotic stem cell lines with potential for therapy. Nature Biotechnology, 25(1), 100–106.

    PubMed  Google Scholar 

  70. Bottai, D., Cigognini, D., Nicora, E., Moro, M., Grimoldi, M. G., Adami, R., Abrignani, S., Marconi, A. M., Di Giulio, A. M., & Gorio, A. (2012). Third trimester amniotic fluid cells with the capacity to develop neural phenotypes and with heterogeneity among sub-populations. Restorative Neurology and Neuroscience, 30(1), 55–68.

    PubMed  Google Scholar 

  71. Bottai, D., Scesa, G., Cigognini, D., Adami, R., Nicora, E., Abrignani, S., Di Giulio, A. M., & Gorio, A. (2014). Third trimester NG2-positive amniotic fluid cells are effective in improving repair in spinal cord injury. Experimental Neurology, 254, 121–133.

    CAS  PubMed  Google Scholar 

  72. Cooper, R. N., Butler-Browne, G. S., & Mouly, V. (2006). Human muscle stem cells. Current Opinion in Pharmacology, 6(3), 295–300.

    CAS  PubMed  Google Scholar 

  73. Reynolds, B. A., & Weiss, S. (1992). Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science, 255(5052), 1707–1710.

    CAS  PubMed  Google Scholar 

  74. Vescovi, A. L., Parati, E. A., Gritti, A., Poulin, P., Ferrario, M., Wanke, E., Frolichsthal-Schoeller, P., Cova, L., Arcellana-Panlilio, M., Colombo, A., & Galli, R. (1999). Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation. Experimental Neurology, 156(1), 71–83.

    CAS  PubMed  Google Scholar 

  75. Gage, F. H. (2000). Mammalian neural stem cells. Science, 287(5457), 1433–1438.

    CAS  PubMed  Google Scholar 

  76. Daniela, F., Vescovi, A. L., & Bottai, D. (2007). The stem cells as a potential treatment for neurodegeneration. Methods in Molecular Biology, 399, 199–213.

    PubMed  Google Scholar 

  77. Adami, R., Scesa, G., & Bottai, D. (2014). Stem cell transplantation in neurological diseases: improving effectiveness in animal models. Frontiers in Cell and Development Biology, 2, 17.

    Google Scholar 

  78. Adami, R., Pagano, J., Colombo, M., Platonova, N., Recchia, D., Chiaramonte, R., Bottinelli, R., Canepari, M., & Bottai, D. (2018). Reduction of Movement in Neurological Diseases: Effects on Neural Stem Cells Characteristics. Frontiers in Neuroscience, 12, 336.

    PubMed  PubMed Central  Google Scholar 

  79. Bottai, D., Adami, R., & Ghidoni, R. (2018). Glycosphingolipids and Neural Stem Cells. Journal of Neurochemistry, 148(6), 698–711.

    PubMed  Google Scholar 

  80. Bottai, D., Spreafico, M., Pistocchi, A., Fazio, G., Adami, R., Grazioli, P., Canu, A., Bragato, C., Rigamonti, S., Parodi, C., Cazzaniga, G., Biondi, A., Cotelli, F., Selicorni, A., & Massa, V. (2018). Modeling Cornelia de Lange Syndrome in vitro and in vivo reveals a role for cohesin complex in neuronal survival and differentiation. Human Molecular Genetics, 28(1), 64–73.

    Google Scholar 

  81. Maherali, N., Sridharan, R., Xie, W., Utikal, J., Eminli, S., Arnold, K., Stadtfeld, M., Yachechko, R., Tchieu, J., Jaenisch, R., Plath, K., & Hochedlinger, K. (2007). Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell, 1(1), 55–70.

    CAS  PubMed  Google Scholar 

  82. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5), 861–872.

    CAS  PubMed  Google Scholar 

  83. Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., Hochedlinger, K., Bernstein, B. E., & Jaenisch, R. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature, 448(7151), 318–324.

    CAS  PubMed  Google Scholar 

  84. Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., Slukvin, I. I., & Thomson, J. A. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318(5858), 1917–1920.

    CAS  PubMed  Google Scholar 

  85. Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T., & Yamanaka, S. (2008). Generation of mouse induced pluripotent stem cells without viral vectors. Science, 322(5903), 949–953.

    CAS  PubMed  Google Scholar 

  86. Park, I. H., Lerou, P. H., Zhao, R., Huo, H., & Daley, G. Q. (2008). Generation of human-induced pluripotent stem cells. Nature Protocols, 3(7), 1180–1186.

    CAS  PubMed  Google Scholar 

  87. Park, I. H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H., Ince, T. A., Lerou, P. H., Lensch, M. W., & Daley, G. Q. (2008). Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 451(7175), 141–146.

    CAS  PubMed  Google Scholar 

  88. Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G., & Hochedlinger, K. (2008). Induced pluripotent stem cells generated without viral integration. Science, 322(5903), 945–949.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Okita, K., Matsumura, Y., Sato, Y., Okada, A., Morizane, A., Okamoto, S., Hong, H., Nakagawa, M., Tanabe, K., Tezuka, K., Shibata, T., Kunisada, T., Takahashi, M., Takahashi, J., Saji, H., & Yamanaka, S. (2011). A more efficient method to generate integration-free human iPS cells. Nature Methods, 8(5), 409–412.

    CAS  PubMed  Google Scholar 

  90. Yoshioka, N., Gros, E., Li, H. R., Kumar, S., Deacon, D. C., Maron, C., Muotri, A. R., Chi, N. C., Fu, X. D., Yu, B. D., & Dowdy, S. F. (2013). Efficient generation of human iPSCs by a synthetic self-replicative RNA. Cell Stem Cell, 13(2), 246–254.

    CAS  PubMed  Google Scholar 

  91. Carey, B. W., Markoulaki, S., Hanna, J., Saha, K., Gao, Q., Mitalipova, M., & Jaenisch, R. (2009). Reprogramming of murine and human somatic cells using a single polycistronic vector. Proceedings of the National Academy of Sciences of the United States of America, 106(1), 157–162.

    CAS  PubMed  Google Scholar 

  92. Chang, C. W., Lai, Y. S., Pawlik, K. M., Liu, K., Sun, C. W., Li, C., Schoeb, T. R., & Townes, T. M. (2009). Polycistronic lentiviral vector for "hit and run" reprogramming of adult skin fibroblasts to induced pluripotent stem cells. Stem Cells, 27(5), 1042–1049.

    CAS  PubMed  Google Scholar 

  93. Anokye-Danso, F., Trivedi, C. M., Juhr, D., Gupta, M., Cui, Z., Tian, Y., Zhang, Y., Yang, W., Gruber, P. J., Epstein, J. A., & Morrisey, E. E. (2011). Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell, 8(4), 376–388.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Seo, B. J., Hong, Y. J., & Do, J. T. (2017). Cellular reprogramming using protein and cell-penetrating peptides. International Journal of Molecular Sciences, 18(3). https://doi.org/10.3390/ijms18030552. 

    PubMed Central  Google Scholar 

  95. Pappas, J. J., & Yang, P. C. (2008). Human ESC vs. iPSC-pros and cons. Journal of Cardiovascular Translational Research, 1(2), 96–99.

    PubMed  Google Scholar 

  96. Li, Y., Balasubramanian, U., Cohen, D., Zhang, P. W., Mosmiller, E., Sattler, R., Maragakis, N. J., & Rothstein, J. D. (2015). A comprehensive library of familial human amyotrophic lateral sclerosis induced pluripotent stem cells. PLoS One, 10(3), e0118266.

    PubMed  PubMed Central  Google Scholar 

  97. Jaiswal, M. K. (2017). Therapeutic opportunities and challenges of induced pluripotent stem cells-derived motor neurons for treatment of amyotrophic lateral sclerosis and motor neuron disease. Neural Regeneration Research, 12(5), 723–736.

    PubMed  PubMed Central  Google Scholar 

  98. Madill, M., McDonagh, K., Ma, J., Vajda, A., McLoughlin, P., O'Brien, T., Hardiman, O., & Shen, S. (2017). Amyotrophic lateral sclerosis patient iPSC-derived astrocytes impair autophagy via non-cell autonomous mechanisms. Molecular Brain, 10(1), 22.

    PubMed  PubMed Central  Google Scholar 

  99. Terzic, D., Maxon, J. R., Krevitt, L., DiBartolomeo, C., Goyal, T., Low, W. C., Dutton, J. R., & Parr, A. M. (2016). Directed Differentiation of Oligodendrocyte Progenitor Cells From Mouse Induced Pluripotent Stem Cells. Cell Transplantation, 25(2), 411–424.

    PubMed  Google Scholar 

  100. Xie, C., Liu, Y. Q., Guan, Y. T., & Zhang, G. X. (2016). Induced Stem Cells as a Novel Multiple Sclerosis Therapy. Current Stem Cell Research & Therapy, 11(4), 313–320.

    CAS  Google Scholar 

  101. Nicaise, A. M., Banda, E., Guzzo, R. M., Russomanno, K., Castro-Borrero, W., Willis, C. M., Johnson, K. M., Lo, A. C., & Crocker, S. J. (2017). iPS-derived neural progenitor cells from PPMS patients reveal defect in myelin injury response. Experimental Neurology, 288, 114–121.

    CAS  PubMed  Google Scholar 

  102. Rinaldi, F., & Caldwell, M. A. (2013). Modeling astrocytic contribution toward neurodegeneration with pluripotent stem cells: focus on Alzheimer's and Parkinson's diseases. Neuroreport, 24(18), 1053–1057.

    CAS  PubMed  Google Scholar 

  103. Majolo, F., Marinowic, D. R., Machado, D. C., & Da Costa, J. C. (2019). Important advances in Alzheimer's disease from the use of induced pluripotent stem cells. Journal of Biomedical Science, 26(1), 15.

    PubMed  PubMed Central  Google Scholar 

  104. Peteri, U. K., Niukkanen, M., & Castren, M. L. (2019). Astrocytes in Neuropathologies Affecting the Frontal Cortex. Frontiers in Cellular Neuroscience, 13, 44.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Daadi, M. M. (2019). Differentiation of Neural Stem Cells Derived from Induced Pluripotent Stem Cells into Dopaminergic Neurons. Methods in Molecular Biology, 1919, 89–96.

    CAS  PubMed  Google Scholar 

  106. Stoddard-Bennett, T., & Reijo Pera, R. (2019). Treatment of Parkinson's Disease through Personalized Medicine and Induced Pluripotent Stem Cells. Cells, 8(1). https://doi.org/10.3390/cells8010026.

    CAS  PubMed Central  Google Scholar 

  107. Abad, M., Mosteiro, L., Pantoja, C., Canamero, M., Rayon, T., Ors, I., Grana, O., Megias, D., Dominguez, O., Martinez, D., Manzanares, M., Ortega, S., & Serrano, M. (2013). Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature, 502(7471), 340–345.

    CAS  PubMed  Google Scholar 

  108. Chin, M. H., Mason, M. J., Xie, W., Volinia, S., Singer, M., Peterson, C., Ambartsumyan, G., Aimiuwu, O., Richter, L., Zhang, J., Khvorostov, I., Ott, V., Grunstein, M., Lavon, N., Benvenisty, N., Croce, C. M., Clark, A. T., Baxter, T., Pyle, A. D., Teitell, M. A., Pelegrini, M., Plath, K., & Lowry, W. E. (2009). Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell, 5(1), 111–123.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Maherali, N., Ahfeldt, T., Rigamonti, A., Utikal, J., Cowan, C., & Hochedlinger, K. (2008). A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell, 3(3), 340–345.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Aoi, T., Yae, K., Nakagawa, M., Ichisaka, T., Okita, K., Takahashi, K., Chiba, T., & Yamanaka, S. (2008). Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science, 321(5889), 699–702.

    CAS  PubMed  Google Scholar 

  111. Miura, K., Okada, Y., Aoi, T., Okada, A., Takahashi, K., Okita, K., Nakagawa, M., Koyanagi, M., Tanabe, K., Ohnuki, M., Ogawa, D., Ikeda, E., Okano, H., & Yamanaka, S. (2009). Variation in the safety of induced pluripotent stem cell lines. Nature Biotechnology, 27(8), 743–745.

    CAS  PubMed  Google Scholar 

  112. Charalambous, M., da Rocha, S. T., & Ferguson-Smith, A. C. (2007). Genomic imprinting, growth control and the allocation of nutritional resources: consequences for postnatal life. Current Opinion in Endocrinology, Diabetes, and Obesity, 14(1), 3–12.

    CAS  PubMed  Google Scholar 

  113. Wilkinson, L. S., Davies, W., & Isles, A. R. (2007). Genomic imprinting effects on brain development and function. Nature Reviews. Neuroscience, 8(11), 832–843.

    CAS  PubMed  Google Scholar 

  114. da Rocha, S. T., Edwards, C. A., Ito, M., Ogata, T., & Ferguson-Smith, A. C. (2008). Genomic imprinting at the mammalian Dlk1-Dio3 domain. Trends in Genetics, 24(6), 306–316.

    PubMed  Google Scholar 

  115. Stadtfeld, M., Apostolou, E., Akutsu, H., Fukuda, A., Follett, P., Natesan, S., Kono, T., Shioda, T., & Hochedlinger, K. (2010). Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature, 465(7295), 175–181.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Ebert, A. D., Yu, J., Rose, F. F., Jr., Mattis, V. B., Lorson, C. L., Thomson, J. A., & Svendsen, C. N. (2009). Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature, 457(7227), 277–280.

    CAS  PubMed  Google Scholar 

  117. Garbes, L., Heesen, L., Holker, I., Bauer, T., Schreml, J., Zimmermann, K., Thoenes, M., Walter, M., Dimos, J., Peitz, M., Brustle, O., Heller, R., & Wirth, B. (2013). VPA response in SMA is suppressed by the fatty acid translocase CD36. Human Molecular Genetics, 22(2), 398–407.

    CAS  PubMed  Google Scholar 

  118. Vazquez-Arango, P., Vowles, J., Browne, C., Hartfield, E., Fernandes, H. J., Mandefro, B., Sareen, D., James, W., Wade-Martins, R., Cowley, S. A., Murphy, S., & O'Reilly, D. (2016). Variant U1 snRNAs are implicated in human pluripotent stem cell maintenance and neuromuscular disease. Nucleic Acids Research, 44(22), 10960–10973.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Luo, Y., Fan, Y., Chen, X., Yu, B., Yue, L., Wang, D., Li, Q., Chen, Y., & Sun, X. (2012). Generation of Induced Pluripotent Stem Cells from Asian Patients with Chronic Neurodegenerative Diseases. The Journal of Reproduction and Development, 58(5), 515–521.

    CAS  PubMed  Google Scholar 

  120. Spitalieri, P., Talarico, R. V., Botta, A., Murdocca, M., D'Apice, M. R., Orlandi, A., Giardina, E., Santoro, M., Brancati, F., Novelli, G., & Sangiuolo, F. (2015). Generation of Human Induced Pluripotent Stem Cells from Extraembryonic Tissues of Fetuses Affected by Monogenic Diseases. Cellular Reprogramming, 17(4), 275–287.

    CAS  PubMed  Google Scholar 

  121. Murdocca, M., Ciafre, S. A., Spitalieri, P., Talarico, R. V., Sanchez, M., Novelli, G., & Sangiuolo, F. (2016). SMA Human iPSC-Derived Motor Neurons Show Perturbed Differentiation and Reduced miR-335-5p Expression. International Journal of Molecular Sciences, 17(8). https://doi.org/10.3390/ijms17081231.

    PubMed Central  Google Scholar 

  122. Lin, X., Li, J. J., Qian, W. J., Zhang, Q. J., Wang, Z. F., Lu, Y. Q., Dong, E. L., He, J., Wang, N., Ma, L. X., & Chen, W. J. (2017). Modeling the differential phenotypes of spinal muscular atrophy with high-yield generation of motor neurons from human induced pluripotent stem cells. Oncotarget, 8(26), 42030–42042.

    PubMed  PubMed Central  Google Scholar 

  123. Feng, M., Liu, C., Xia, Y., Liu, B., Zhou, M., Li, Z., Sun, Q., Hu, Z., Wang, Y., Wu, L., Liu, X., & Liang, D. (2018). Restoration of SMN expression in mesenchymal stem cells derived from gene-targeted patient-specific iPSCs. Journal of Molecular Histology, 49(1), 27–37.

    CAS  PubMed  Google Scholar 

  124. Hosoyama, T., McGivern, J. V., Van Dyke, J. M., Ebert, A. D., & Suzuki, M. (2014). Derivation of myogenic progenitors directly from human pluripotent stem cells using a sphere-based culture. Stem Cells Translational Medicine, 3(5), 564–574.

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Hor, J. H., Soh, E. S., Tan, L. Y., Lim, V. J. W., Santosa, M. M., Winanto, Ho, B. X., Fan, Y., Soh, B. S., Ng, S. Y. (2018). Cell cycle inhibitors protect motor neurons in an organoid model of Spinal Muscular Atrophy Cell Death & Disease, 9(11), 1100. https://doi.org/10.1038/s41419-018-1081-0.

  126. Chang, T., Zheng, W., Tsark, W., Bates, S., Huang, H., Lin, R. J., & Yee, J. K. (2011). Brief report: phenotypic rescue of induced pluripotent stem cell-derived motoneurons of a spinal muscular atrophy patient. Stem Cells, 29(12), 2090–2093.

    CAS  PubMed  Google Scholar 

  127. Sareen, D., Ebert, A. D., Heins, B. M., McGivern, J. V., Ornelas, L., & Svendsen, C. N. (2012). Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy. PLoS One, 7(6), e39113.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Corti, S., Nizzardo, M., Simone, C., Falcone, M., Nardini, M., Ronchi, D., Donadoni, C., Salani, S., Riboldi, G., Magri, F., Menozzi, G., Bonaglia, C., Rizzo, F., Bresolin, N., & Comi, G. P. (2012). Genetic correction of human induced pluripotent stem cells from patients with spinal muscular atrophy. Science Translational Medicine, 4(165), 165ra162.

    PubMed  PubMed Central  Google Scholar 

  129. McGivern, J. V., Patitucci, T. N., Nord, J. A., Barabas, M. A., Stucky, C. L., & Ebert, A. D. (2013). Spinal muscular atrophy astrocytes exhibit abnormal calcium regulation and reduced growth factor production. Glia, 61(9), 1418–1428.

    PubMed  PubMed Central  Google Scholar 

  130. Schwab, A. J., & Ebert, A. D. (2014). Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy. PLoS One, 9(7), e103112.

    PubMed  PubMed Central  Google Scholar 

  131. Rindt, H., Feng, Z., Mazzasette, C., Glascock, J. J., Valdivia, D., Pyles, N., Crawford, T. O., Swoboda, K. J., Patitucci, T. N., Ebert, A. D., Sumner, C. J., Ko, C. P., & Lorson, C. L. (2015). Astrocytes influence the severity of spinal muscular atrophy. Human Molecular Genetics, 24(14), 4094–4102.

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Yoshida, M., Kitaoka, S., Egawa, N., Yamane, M., Ikeda, R., Tsukita, K., Amano, N., Watanabe, A., Morimoto, M., Takahashi, J., Hosoi, H., Nakahata, T., Inoue, H., & Saito, M. K. (2015). Modeling the early phenotype at the neuromuscular junction of spinal muscular atrophy using patient-derived iPSCs. Stem Cell Reports, 4(4), 561–568.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Boza-Moran, M. G., Martinez-Hernandez, R., Bernal, S., Wanisch, K., Also-Rallo, E., Le Heron, A., Alias, L., Denis, C., Girard, M., Yee, J. K., Tizzano, E. F., & Yanez-Munoz, R. J. (2015). Decay in survival motor neuron and plastin 3 levels during differentiation of iPSC-derived human motor neurons. Scientific Reports, 5, 11696.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Liu, H., Lu, J., Chen, H., Du, Z., Li, X. J., & Zhang, S. C. (2015). Spinal muscular atrophy patient-derived motor neurons exhibit hyperexcitability. Scientific Reports, 5, 12189.

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Ng, S. Y., Soh, B. S., Rodriguez-Muela, N., Hendrickson, D. G., Price, F., Rinn, J. L., & Rubin, L. L. (2015). Genome-wide RNA-Seq of Human Motor Neurons Implicates Selective ER Stress Activation in Spinal Muscular Atrophy. Cell Stem Cell, 17(5), 569–584.

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Nizzardo, M., Simone, C., Dametti, S., Salani, S., Ulzi, G., Pagliarani, S., Rizzo, F., Frattini, E., Pagani, F., Bresolin, N., Comi, G., & Corti, S. (2015). Spinal muscular atrophy phenotype is ameliorated in human motor neurons by SMN increase via different novel RNA therapeutic approaches. Scientific Reports, 5, 11746.

    PubMed  PubMed Central  Google Scholar 

  137. Fuller, H. R., Mandefro, B., Shirran, S. L., Gross, A. R., Kaus, A. S., Botting, C. H., Morris, G. E., & Sareen, D. (2016). Spinal Muscular Atrophy Patient iPSC-Derived Motor Neurons Have Reduced Expression of Proteins Important in Neuronal Development. Frontiers in Cellular Neuroscience, 9, 506.

    PubMed  PubMed Central  Google Scholar 

  138. Patitucci, T. N., & Ebert, A. D. (2016). SMN deficiency does not induce oxidative stress in SMA iPSC-derived astrocytes or motor neurons. Human Molecular Genetics, 25(3), 514–523.

    CAS  PubMed  Google Scholar 

  139. Powis, R. A., Karyka, E., Boyd, P., Come, J., Jones, R. A., Zheng, Y., Szunyogova, E., Groen, E. J., Hunter, G., Thomson, D., Wishart, T. M., Becker, C. G., Parson, S. H., Martinat, C., Azzouz, M., & Gillingwater, T. H. (2016). Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy. JCI Insight, 1(11), e87908.

    PubMed  PubMed Central  Google Scholar 

  140. Heesen, L., Peitz, M., Torres-Benito, L., Holker, I., Hupperich, K., Dobrindt, K., Jungverdorben, J., Ritzenhofen, S., Weykopf, B., Eckert, D., Hosseini-Barkooie, S. M., Storbeck, M., Fusaki, N., Lonigro, R., Heller, R., Kye, M. J., Brustle, O., & Wirth, B. (2016). Plastin 3 is upregulated in iPSC-derived motoneurons from asymptomatic SMN1-deleted individuals. Cellular and Molecular Life Sciences, 73(10), 2089–2104.

    CAS  PubMed  Google Scholar 

  141. Osman, E. Y., Washington, C. W., 3rd, Kaifer, K. A., Mazzasette, C., Patitucci, T. N., Florea, K. M., Simon, M. E., Ko, C. P., Ebert, A. D., & Lorson, C. L. (2016). Optimization of Morpholino Antisense Oligonucleotides Targeting the Intronic Repressor Element1 in Spinal Muscular Atrophy. Molecular Therapy, 24(9), 1592–1601.

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Ohuchi, K., Funato, M., Kato, Z., Seki, J., Kawase, C., Tamai, Y., Ono, Y., Nagahara, Y., Noda, Y., Kameyama, T., Ando, S., Tsuruma, K., Shimazawa, M., Hara, H., & Kaneko, H. (2016). Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog. Stem Cells Translational Medicine, 5(2), 152–163.

    CAS  PubMed  Google Scholar 

  143. Martin, J. E., Nguyen, T. T., Grunseich, C., Nofziger, J. H., Lee, P. R., Fields, D., Fischbeck, K. H., & Foran, E. (2017). Decreased Motor Neuron Support by SMA Astrocytes due to Diminished MCP1 Secretion. The Journal of Neuroscience, 37(21), 5309–5318.

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Ando, S., Funato, M., Ohuchi, K., Kameyama, T., Inagaki, S., Seki, J., Kawase, C., Tsuruma, K., Shimazawa, M., Kaneko, H., & Hara, H. (2017). Edaravone is a candidate agent for spinal muscular atrophy: In vitro analysis using a human induced pluripotent stem cells-derived disease model. European Journal of Pharmacology, 814, 161–168.

    CAS  PubMed  Google Scholar 

  145. Woo, C. J., Maier, V. K., Davey, R., Brennan, J., Li, G., Brothers, J., 2nd, Schwartz, B., Gordo, S., Kasper, A., Okamoto, T. R., Johansson, H. E., Mandefro, B., Sareen, D., Bialek, P., Chau, B. N., Bhat, B., Bullough, D., & Barsoum, J. (2017). Gene activation of SMN by selective disruption of lncRNA-mediated recruitment of PRC2 for the treatment of spinal muscular atrophy. Proceedings of the National Academy of Sciences of the United States of America, 114(8), E1509–E1518.

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Palomo, V., Perez, D. I., Roca, C., Anderson, C., Rodriguez-Muela, N., Perez, C., Morales-Garcia, J. A., Reyes, J. A., Campillo, N. E., Perez-Castillo, A. M., Rubin, L. L., Timchenko, L., Gil, C., & Martinez, A. (2017). Subtly Modulating Glycogen Synthase Kinase 3 beta: Allosteric Inhibitor Development and Their Potential for the Treatment of Chronic Diseases. Journal of Medicinal Chemistry, 60(12), 4983–5001.

    CAS  PubMed  Google Scholar 

  147. Sison, S. L., Patitucci, T. N., Seminary, E. R., Villalon, E., Lorson, C. L., & Ebert, A. D. (2017). Astrocyte-produced miR-146a as a mediator of motor neuron loss in spinal muscular atrophy. Human Molecular Genetics, 26(17), 3409–3420.

    CAS  PubMed  Google Scholar 

  148. Lai, J. I., Leman, L. J., Ku, S., Vickers, C. J., Olsen, C. A., Montero, A., Ghadiri, M. R., & Gottesfeld, J. M. (2017). Cyclic tetrapeptide HDAC inhibitors as potential therapeutics for spinal muscular atrophy: Screening with iPSC-derived neuronal cells. Bioorganic & Medicinal Chemistry Letters, 27(15), 3289–3293.

    CAS  Google Scholar 

  149. d'Ydewalle, C., Ramos, D. M., Pyles, N. J., Ng, S. Y., Gorz, M., Pilato, C. M., Ling, K., Kong, L., Ward, A. J., Rubin, L. L., Rigo, F., Bennett, C. F., & Sumner, C. J. (2017). The Antisense Transcript SMN-AS1 Regulates SMN Expression and Is a Novel Therapeutic Target for Spinal Muscular Atrophy. Neuron, 93(1), 66–79.

    CAS  PubMed  Google Scholar 

  150. Zhou, M., Hu, Z., Qiu, L., Zhou, T., Feng, M., Hu, Q., Zeng, B., Li, Z., Sun, Q., Wu, Y., Liu, X., Wu, L., & Liang, D. (2018). Seamless Genetic Conversion of SMN2 to SMN1 via CRISPR/Cpf1 and Single-Stranded Oligodeoxynucleotides in Spinal Muscular Atrophy Patient-Specific Induced Pluripotent Stem Cells. Human Gene Therapy, 29(11), 1252–1263.

    CAS  PubMed  Google Scholar 

  151. Ramirez, A., Crisafulli, S. G., Rizzuti, M., Bresolin, N., Comi, G. P., Corti, S., & Nizzardo, M. (2018). Investigation of New Morpholino Oligomers to Increase Survival Motor Neuron Protein Levels in Spinal Muscular Atrophy. International Journal of Molecular Sciences, 19(1). https://doi.org/10.3390/ijms19010167.

    PubMed Central  Google Scholar 

  152. Ohuchi, K., Funato, M., Ando, S., Inagaki, S., Sato, A., Kawase, C., Seki, J., Nakamura, S., Shimazawa, M., Kaneko, H., & Hara, H. (2019). Impairment of oligodendrocyte lineages in spinal muscular atrophy model systems. Neuroreport, 30(5), 350–357.

    CAS  PubMed  Google Scholar 

  153. Son, Y. S., Choi, K., Lee, H., Kwon, O., Jung, K. B., Cho, S., Baek, J., Son, B., Kang, S. M., Kang, M., Yoon, J., Shen, H., Lee, S., Oh, J. H., Lee, H. A., Lee, M. O., Cho, H. S., Jung, C. R., Kim, J., Cho, S., & Son, M. Y. (2019). A SMN2 Splicing Modifier Rescues the Disease Phenotypes in an In Vitro Human Spinal Muscular Atrophy Model. Stem Cells and Development, 28(7), 438–453.

    CAS  PubMed  Google Scholar 

  154. Sareen, D., van Ginkel, P. R., Takach, J. C., Mohiuddin, A., Darjatmoko, S. R., Albert, D. M., & Polans, A. S. (2006). Mitochondria as the primary target of resveratrol-induced apoptosis in human retinoblastoma cells. Investigative Ophthalmology & Visual Science, 47(9), 3708–3716.

    Google Scholar 

  155. Kramer, N. J., & Gitler, A. D. (2017). Raise the Roof: Boosting the Efficacy of a Spinal Muscular Atrophy Therapy. Neuron, 93(1), 3–5.

    CAS  PubMed  Google Scholar 

  156. Ackermann, B., Krober, S., Torres-Benito, L., Borgmann, A., Peters, M., Hosseini Barkooie, S. M., Tejero, R., Jakubik, M., Schreml, J., Milbradt, J., Wunderlich, T. F., Riessland, M., Tabares, L., & Wirth, B. (2013). Plastin 3 ameliorates spinal muscular atrophy via delayed axon pruning and improves neuromuscular junction functionality. Human Molecular Genetics, 22(7), 1328–1347.

    CAS  PubMed  Google Scholar 

  157. Oprea, G. E., Krober, S., McWhorter, M. L., Rossoll, W., Muller, S., Krawczak, M., Bassell, G. J., Beattie, C. E., & Wirth, B. (2008). Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy. Science, 320(5875), 524–527.

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Bernal, S., Also-Rallo, E., Martinez-Hernandez, R., Alias, L., Rodriguez-Alvarez, F. J., Millan, J. M., Hernandez-Chico, C., Baiget, M., & Tizzano, E. F. (2011). Plastin 3 expression in discordant spinal muscular atrophy (SMA) siblings. Neuromuscular Disorders, 21(6), 413–419.

    PubMed  Google Scholar 

  159. Gabanella, F., Butchbach, M. E., Saieva, L., Carissimi, C., Burghes, A. H., & Pellizzoni, L. (2007). Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of spliceosomal snRNPs. PLoS One, 2(9), e921.

    PubMed  PubMed Central  Google Scholar 

  160. Bach, J. R. (2007). Medical considerations of long-term survival of Werdnig-Hoffmann disease. American Journal of Physical Medicine & Rehabilitation, 86(5), 349–355.

    Google Scholar 

  161. Moller, P., Moe, N., Saugstad, O. D., Skullerud, K., Velken, M., Berg, K., Nitter-Hauge, S., & Borresen, A. L. (1990). Spinal muscular atrophy type I combined with atrial septal defect in three sibs. Clinical Genetics, 38(2), 81–83.

    CAS  PubMed  Google Scholar 

  162. Tein, I., Sloane, A. E., Donner, E. J., Lehotay, D. C., Millington, D. S., & Kelley, R. I. (1995). Fatty acid oxidation abnormalities in childhood-onset spinal muscular atrophy: primary or secondary defect(s)? Pediatric Neurology, 12(1), 21–30.

    CAS  PubMed  Google Scholar 

  163. Shababi, M., Lorson, C. L., & Rudnik-Schoneborn, S. S. (2014). Spinal muscular atrophy: a motor neuron disorder or a multi-organ disease? Journal of Anatomy, 224(1), 15–28.

    CAS  PubMed  Google Scholar 

  164. Park, G. H., Maeno-Hikichi, Y., Awano, T., Landmesser, L. T., & Monani, U. R. (2010). Reduced survival of motor neuron (SMN) protein in motor neuronal progenitors functions cell autonomously to cause spinal muscular atrophy in model mice expressing the human centromeric (SMN2) gene. The Journal of Neuroscience, 30(36), 12005–12019.

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Tong, X., Ao, Y., Faas, G. C., Nwaobi, S. E., Xu, J., Haustein, M. D., Anderson, M. A., Mody, I., Olsen, M. L., Sofroniew, M. V., & Khakh, B. S. (2014). Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington's disease model mice. Nature Neuroscience, 17(5), 694–703.

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Wolf, G. (2003). Growth factors and the development of diabetic nephropathy. Current Diabetes Reports, 3(6), 485–490.

    PubMed  Google Scholar 

  167. He, Y., Huang, C., Sun, X., Long, X. R., Lv, X. W., & Li, J. (2012). MicroRNA-146a modulates TGF-beta1-induced hepatic stellate cell proliferation by targeting SMAD4. Cellular Signalling, 24(10), 1923–1930.

    CAS  PubMed  Google Scholar 

  168. Huang, C., Day, M. L., Poronnik, P., Pollock, C. A., & Chen, X. M. (2014). Inhibition of KCa3.1 suppresses TGF-beta1 induced MCP-1 expression in human proximal tubular cells through Smad3, p38 and ERK1/2 signaling pathways. The International Journal of Biochemistry & Cell Biology, 47, 1–10.

    CAS  Google Scholar 

  169. Martinez-Hernandez, R., Bernal, S., Alias, L., & Tizzano, E. F. (2014). Abnormalities in early markers of muscle involvement support a delay in myogenesis in spinal muscular atrophy. Journal of Neuropathology and Experimental Neurology, 73(6), 559–567.

    CAS  PubMed  Google Scholar 

  170. Valsecchi, V., Boido, M., De Amicis, E., Piras, A., & Vercelli, A. (2015). Expression of Muscle-Specific MiRNA 206 in the Progression of Disease in a Murine SMA Model. PLoS One, 10(6), e0128560.

    PubMed  PubMed Central  Google Scholar 

  171. Ripolone, M., Ronchi, D., Violano, R., Vallejo, D., Fagiolari, G., Barca, E., Lucchini, V., Colombo, I., Villa, L., Berardinelli, A., Balottin, U., Morandi, L., Mora, M., Bordoni, A., Fortunato, F., Corti, S., Parisi, D., Toscano, A., Sciacco, M., DiMauro, S., Comi, G. P., & Moggio, M. (2015). Impaired Muscle Mitochondrial Biogenesis and Myogenesis in Spinal Muscular Atrophy. JAMA Neurology, 72(6), 666–675.

    PubMed  PubMed Central  Google Scholar 

  172. Fayzullina, S., & Martin, L. J. (2016). DNA Damage Response and DNA Repair in Skeletal Myocytes From a Mouse Model of Spinal Muscular Atrophy. Journal of Neuropathology and Experimental Neurology, 75(9), 889–902.

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Riessland, M., Brichta, L., Hahnen, E., & Wirth, B. (2006). The benzamide M344, a novel histone deacetylase inhibitor, significantly increases SMN2 RNA/protein levels in spinal muscular atrophy cells. Human Genetics, 120(1), 101–110.

    CAS  PubMed  Google Scholar 

  174. Avila, A. M., Burnett, B. G., Taye, A. A., Gabanella, F., Knight, M. A., Hartenstein, P., Cizman, Z., Di Prospero, N. A., Pellizzoni, L., Fischbeck, K. H., & Sumner, C. J. (2007). Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy. The Journal of Clinical Investigation, 117(3), 659–671.

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Mercuri, E., Bertini, E., Messina, S., Solari, A., D'Amico, A., Angelozzi, C., Battini, R., Berardinelli, A., Boffi, P., Bruno, C., Cini, C., Colitto, F., Kinali, M., Minetti, C., Mongini, T., Morandi, L., Neri, G., Orcesi, S., Pane, M., Pelliccioni, M., Pini, A., Tiziano, F. D., Villanova, M., Vita, G., & Brahe, C. (2007). Randomized, double-blind, placebo-controlled trial of phenylbutyrate in spinal muscular atrophy. Neurology, 68(1), 51–55.

    CAS  PubMed  Google Scholar 

  176. Swoboda, K. J., Scott, C. B., Crawford, T. O., Simard, L. R., Reyna, S. P., Krosschell, K. J., Acsadi, G., Elsheik, B., Schroth, M. K., D'Anjou, G., LaSalle, B., Prior, T. W., Sorenson, S. L., Maczulski, J. A., Bromberg, M. B., Chan, G. M., & Kissel, J. T. (2010). SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy. PLoS One, 5(8), e12140.

    PubMed  PubMed Central  Google Scholar 

  177. Evans, M. C., Cherry, J. J., & Androphy, E. J. (2011). Differential regulation of the SMN2 gene by individual HDAC proteins. Biochemical and Biophysical Research Communications, 414(1), 25–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  178. Nizzardo, M., Simone, C., Salani, S., Ruepp, M. D., Rizzo, F., Ruggieri, M., Zanetta, C., Brajkovic, S., Moulton, H. M., Muehlemann, O., Bresolin, N., Comi, G. P., & Corti, S. (2014). Effect of combined systemic and local morpholino treatment on the spinal muscular atrophy Delta7 mouse model phenotype. Clinical Therapeutics, 36(3), 340–356 e345.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Damian Randle’s proofreading and editorial service for the academic world and for business in the United Kingdom and Europe (http://englishedituk.co.uk) for the complete revision of the manuscript.

Funding

The work was supported by a grant to Daniele Bottai from Asamsi ONLUS via Prosciutta, 23–48018 Faenza (RA), Italy.

Author information

Authors and Affiliations

  1. Department of Health Sciences, University of Milan, via A. di Rudinì 8, 20142, Milan, Italy

    Raffaella Adami & Daniele Bottai

Authors
  1. Raffaella Adami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniele Bottai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniele Bottai.

Ethics declarations

Conflict of Interest

The authors declare that this research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Adami, R., Bottai, D. Spinal Muscular Atrophy Modeling and Treatment Advances by Induced Pluripotent Stem Cells Studies. Stem Cell Rev and Rep 15, 795–813 (2019). https://doi.org/10.1007/s12015-019-09910-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-019-09910-6

Keywords

Search

Navigation