Otizm Spektrum Bozukluğu ve Kök Hücre Tedavisi

Özet

Referanslar

Paprocka J, Kaminiów K, Kozak S, Sztuba K, Emich-Widera E. Stem Cell Therapies for Cerebral Palsy and Autism Spectrum Disorder-A Systematic Review. Brain Sci. 2021 Dec 3;11(12):1606. doi: 10.3390/brainsci11121606.

Nabetani M, Mukai T, Taguchi A. Cell Therapies for Autism Spectrum Disorder Based on New Pathophysiology: A Review. Cell Transplant. 2023 Jan-Dec;32:9636897231163217. doi: 10.1177/09636897231163217.

Diagnostic Criteria for ASD. Health Care ProvidersMay 8, 2025. https://www.cdc.gov/autism/ hcp/diagnosis/index.html.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5-TR. 5th ed. American Psychiatric Association Publishing; Washington, DC, USA: 2022. https://doi.org/10.1176/appi.books.9780890425787. [Google Scholar]

Guthrie W, Wallis K, Bennett A, Brooks E, Dudley J, Gerdes M, Pandey J, Levy SE, Schultz RT, Miller JS. Accuracy of Autism Screening in a Large Pediatric Network. Pediatrics. 2019 Oct;144(4):e20183963. doi: 10.1542/peds.2018-3963.

Blumberg SJ, Bramlett MD, Kogan MD, Schieve LA, Jones JR, Lu MC. Changes in prevalen- ce of parent-reported autism spectrum disorder in school-aged U.S. children: 2007 to 2011- 2012. Natl Health Stat Report. 2013 Mar 20;(65):1-11, 1 p following 11.

Santos JLS, Araújo CA, Rocha CAG, Costa-Ferro ZSM, Souza BSF. Modeling Autism Spect- rum Disorders with Induced Pluripotent Stem Cell-Derived Brain Organoids. Biomolecules. 2023 Jan 30;13(2):260. doi: 10.3390/biom13020260.

Vahia VN. Diagnostic and statistical manual of mental disorders 5: A quick glance. Indian J Psychiatry. 2013 Jul;55(3):220-3. doi: 10.4103/0019-5545.117131.

Maenner MJ, Shaw KA, Bakian AV, Bilder DA, Durkin MS, Esler A, Furnier SM, Hallas L, Hall-Lande J, Hudson A, Hughes MM, Patrick M, Pierce K, Poynter JN, Salinas A, Shenouda J, Vehorn A, Warren Z, Constantino JN, DiRienzo M, Fitzgerald RT, Grzybowski A, Spivey MH, Pettygrove S, Zahorodny W, Ali A, Andrews JG, Baroud T, Gutierrez J, Hewitt A, Lee LC, Lopez M, Mancilla KC, McArthur D, Schwenk YD, Washington A, Williams S, Cogswell ME. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years

- Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2018. MMWR Surveill Summ. 2021 Dec 3;70(11):1-16. doi: 10.15585/mmwr.ss7011a1.

Forsberg SL, Ilieva M, Maria Michel T. Epigenetics and cerebral organoids: promising dire- ctions in autism spectrum disorders. Transl Psychiatry. 2018 Jan 10;8(1):14. doi: 10.1038/ s41398-017-0062-x.

Jia FY, Li TY. Editorial: Etiology and treatment for children and adolescents with autism spe- ctrum disorder. Front Psychiatry. 2023 Jul 13;14:1222384. doi: 10.3389/fpsyt.2023.1222384.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; Washington, DC, USA: 2013. https://doi.org/10.1176/ appi.books.9780890425596. [Google Scholar]

World Health Organization. “ICD-10: The ICD-10 Classification of Mental and Behavioural Disorders: diagnostic criteria for research.” ICD-10: the ICD-10 classification of mental and behavioural disorders: diagnostic criteria for research. World Health Organization; Geneva, Switzerland:1993. xiii + 248 pages. ISBN 92 4154455 4 [Google Scholar]

Roman-Urrestarazu A, van Kessel R, Allison C, Matthews FE, Brayne C, Baron-Cohen S. Association of Race/Ethnicity and Social Disadvantage with Autism Prevalence in 7 million School Children in England. JAMA Pediatr. 2021;175:e210054. doi: 10.1001/jamapediatri- cs.2021.0054.

Morales Hidalgo P., Voltas Moreso N., Canals Sans J. Autism spectrum disorder prevalence and associated sociodemographic factors in the school population: EPINED study. Autism. 2021;25:1999–2011. doi: 10.1177/13623613211007717.

Toro R, Konyukh M, Delorme R, Leblond C, Chaste P, Fauchereau F, Coleman M, Leboyer M, Gillberg C, Bourgeron T. Key role for gene dosage and synaptic homeostasis in autism spect- rum disorders. Trends Genet. 2010;26:363–372. doi: 10.1016/j.tig.2010.05.007.

Nabetani M, Mukai T. Future perspectives on cell therapy for autism spectrum disorder. BIO- CELL, 2022;46(4):873–79. https://doi.org/10.32604/biocell.2022.018218.

Robertson CE, Baron-Cohen S. Sensory perception in autism. Nat Rev Neurosci. 2017 Nov;18(11):671-684. doi: 10.1038/nrn.2017.112.

Mottron L, Dawson M, Soulières I, Hubert B, Burack J. Enhanced perceptual functioning in autism: an update, and eight principles of autistic perception. J Autism Dev Disord. 2006 Jan;36(1):27-43. doi: 10.1007/s10803-005-0040-7.

Demetriou EA, Song CY, Park SH, Pepper KL, Naismith SL, Hermens DF, Hickie IB, Thomas EE, Norton A, White D, Guastella AJ. Autism, Early Psychosis, and Social Anxiety Disorder: a transdiagnostic examination of executive function cognitive circuitry and contribution to disability. Transl Psychiatry. 2018 Sep 24;8(1):200. doi: 10.1038/s41398-018-0193-8.

Jones CRG, Simonoff E, Baird G, Pickles A, Marsden AJS, Tregay J, Happé F, Charman T. The association between theory of mind, executive function, and the symptoms of autism spect- rum disorder. Autism Res. 2018 Jan;11(1):95-109. doi: 10.1002/aur.1873.

Baron-Cohen S, Leslie AM, Frith U. Does the autistic child have a “theory of mind”? Cogniti- on. 1985 Oct;21(1):37-46. doi: 10.1016/0010-0277(85)90022-8.

Sharma A, Gokulchandran N, Sane H, Nivins S, Paranjape A, Badhe P. The Baseline Pattern and Age-related Developmental Metabolic Changes in the Brain of Children with Autism as Measured on Positron Emission Tomography/Computed Tomography Scan. World J Nucl Med. 2018 Apr-Jun;17(2):94-101. doi: 10.4103/wjnm.WJNM_29_17.

Südhof TC. Neuroligins and neurexins link synaptic function to cognitive disease. Nature. 2008 Oct 16;455(7215):903-11. doi: 10.1038/nature07456.

Zoghbi HY, Bear MF. Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities. Cold Spring Harb Perspect Biol. 2012 Mar 1;4(3):a009886. doi: 10.1101/cshperspect.a009886.

Castelbaum L, Sylvester CM, Zhang Y, Yu Q, Constantino JN. On the Nature of Monozygotic Twin Concordance and Discordance for Autistic Trait Severity: A Quantitative Analysis. Be- hav Genet. 2020 Jul;50(4):263-272. doi: 10.1007/s10519-019-09987-2.

Cohen S, Gabel HW, Hemberg M, Hutchinson AN, Sadacca LA, Ebert DH, Harmin DA, Gre- enberg RS, Verdine VK, Zhou Z, Wetsel WC, West AE, Greenberg ME. Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function. Neuron. 2011 Oct 6;72(1):72-85. doi: 10.1016/j.neuron.2011.08.022.

Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol. 2009 May;10(5):307-18. doi: 10.1038/nrm2672.

Budimirovic DB, Kaufmann WE. What can we learn about autism from studying fragile X syndrome? Dev Neurosci. 2011;33(5):379-94. doi: 10.1159/000330213.

Greer PL, Hanayama R, Bloodgood BL, Mardinly AR, Lipton DM, Flavell SW, Kim TK, Grif- fith EC, Waldon Z, Maehr R, Ploegh HL, Chowdhury S, Worley PF, Steen J, Greenberg ME. The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell. 2010 Mar 5;140(5):704-16. doi: 10.1016/j.cell.2010.01.026.

Mabb AM, Ehlers MD. Ubiquitination in postsynaptic function and plasticity. Annu Rev Cell Dev Biol. 2010;26:179-210. doi: 10.1146/annurev-cellbio-100109-104129.

Sassone-Corsi P, Christen Y, editors. A Time for Metabolism and Hormones [Internet]. Cham (CH): Springer; 2016. PMID: 28892333.

Sullivan PF, Geschwind DH. Defining the Genetic, Genomic, Cellular, and Diagnostic Ar- chitectures of Psychiatric Disorders. Cell. 2019 Mar 21;177(1):162-183. doi: 10.1016/j. cell.2019.01.015.

Ruzzo EK, Pérez-Cano L, Jung JY, Wang LK, Kashef-Haghighi D, Hartl C, Singh C, Xu J, Ho- ekstra JN, Leventhal O, Leppä VM, Gandal MJ, Paskov K, Stockham N, Polioudakis D, Lowe JK, Prober DA, Geschwind DH, Wall DP. Inherited and De Novo Genetic Risk for Autism Im- pacts Shared Networks. Cell. 2019 Aug 8;178(4):850-866.e26. doi: 10.1016/j.cell.2019.07.015.

Parikshak NN, Swarup V, Belgard TG, Irimia M, Ramaswami G, Gandal MJ, Hartl C, Leppa V, de la Torre Ubieta L, Huang J, Lowe JK, Blencowe BJ, Horvath S, Geschwind DH. Author Correction: Genome-wide changes in lncRNA, splicing, and regional gene expression patter- ns in autism. Nature. 2018 Aug;560(7718):E30. doi: 10.1038/s41586-018-0295-8. Erratum for: Nature. 2016 Dec 15;540(7633):423-427. doi: 10.1038/nature20612.

Oudin A, Frondelius K, Haglund N, Källén K, Forsberg B, Gustafsson P, Malmqvist E. Prena- tal exposure to air pollution as a potential risk factor for autism and ADHD. Environ Int. 2019 Dec;133(Pt A):105149. doi: 10.1016/j.envint.2019.105149.

Rossignol DA, Genuis SJ, Frye RE. Environmental toxicants and autism spectrum disorders: a systematic review. Transl Psychiatry. 2014 Feb 11;4(2):e360. doi: 10.1038/tp.2014.4.

Volk L, Chiu SL, Sharma K, Huganir RL. Glutamate synapses in human cognitive disorders. Annu Rev Neurosci. 2015 Jul 8;38:127-49. doi: 10.1146/annurev-neuro-071714-033821.

Tachibana Y, Miyazaki C, Ota E, Mori R, Hwang Y, Kobayashi E, Terasaka A, Tang J, Ka- mio Y. A systematic review and meta-analysis of comprehensive interventions for pre-school children with autism spectrum disorder (ASD). PLoS One. 2017 Dec 6;12(12):e0186502. doi: 10.1371/journal.pone.0186502.

Kubota M, Fujino J, Tei S, Takahata K, Matsuoka K, Tagai K, Sano Y, Yamamoto Y, Shimada H, Takado Y, Seki C, Itahashi T, Aoki YY, Ohta H, Hashimoto RI, Zhang MR, Suhara T, Nakamu- ra M, Takahashi H, Kato N, Higuchi M. Binding of Dopamine D1 Receptor and Noradrena- line Transporter in Individuals with Autism Spectrum Disorder: A PET Study. Cereb Cortex. 2020 Nov 3;30(12):6458-6468. doi: 10.1093/cercor/bhaa211.

Takumi T, Tamada K, Hatanaka F, Nakai N, Bolton PF. Behavioral neuroscience of autism. Neurosci Biobehav Rev. 2020 Mar;110:60-76. doi: 10.1016/j.neubiorev.2019.04.012.

Rojas DC. The role of glutamate and its receptors in autism and the use of glutamate receptor antagonists in treatment. J Neural Transm (Vienna). 2014 Aug;121(8):891-905. doi: 10.1007/ s00702-014-1216-0.

Yang JQ, Yang CH, Yin BQ. Combined the GABA-A and GABA-B receptor agonists attenua- tes autistic behaviors in a prenatal valproic acid-induced mouse model of autism. Behav BrainRes. 2021 Apr 9;403:113094. doi: 10.1016/j.bbr.2020.113094.

Sukhodolsky DG, Bloch MH, Panza KE, Reichow B. Cognitive-behavioral therapy for anxiety in children with high-functioning autism: a meta-analysis. Pediatrics. 2013 No- v;132(5):e1341-50. doi: 10.1542/peds.2013-1193.

Minshawi NF. Behavioral assessment and treatment of self-injurious behavior in autism. Child Adolesc Psychiatr Clin N Am. 2008 Oct;17(4):875-86, x. doi: 10.1016/j.chc.2008.06.012.

MacDonald R, Parry-Cruwys D, Dupere S, Ahearn W. Assessing progress and outcome of early intensive behavioral intervention for toddlers with autism. Res Dev Disabil. 2014 Dec;35(12):3632-44. doi: 10.1016/j.ridd.2014.08.036.

Lancaster BM. Assessment and treatment of autism. Indian J Pediatr. 2005 Jan;72(1):45-52. doi: 10.1007/BF02760580.

Huntjens A, van den Bosch LMCW, Sizoo B, Kerkhof A, Huibers MJH, van der Gaag M. The effect of dialectical behaviour therapy in autism spectrum patients with suicidality and/ or self-destructive behaviour (DIASS): study protocol for a multicentre randomised controlled trial. BMC Psychiatry. 2020 Mar 17;20(1):127. doi: 10.1186/s12888-020-02531-1.

Heyvaert M, Saenen L, Campbell JM, Maes B, Onghena P. Efficacy of behavioral interven- tions for reducing problem behavior in persons with autism: an updated quantitative synt- hesis of single-subject research. Res Dev Disabil. 2014 Oct;35(10):2463-76. doi: 10.1016/j. ridd.2014.06.017.

Canpolat M. Pediatrik Nöroloji Hastalarında Kök Hücre Uygulamaları. In, Temel Pediatrik Nöroloji Tanı ve Tedavi (Kumandaş& Canpolat). Akademisyen Kitabevi, 2022. pp.719-746

Üstün CT, Dinç GT. Kök Hücre Bilimlerinde Güncel Tanımlar. In, Canpolat, Çocuk Nörolo- jisi Pratiğinde Kök Hücre Multidisipliner Yaklaşım (Editör: Canpolat M). Akademisyen Kita- bevi, Ankara, ISBN:9786253994099, 2023. pp. 19-29.

Kalra K, Tomar PC, Stem Cell: Basics, Classifi cation and Applications. American Journal of Ph ytomedicine and Clinical Therapeutics (AJPCT), 2014;2(7):919-930.

Marc HGP Raaijmakers. Overview of stem cells. Se ction Editor: Benjamin A Raby, MD, MPH, Deputy Editor: Jennifer S Tirnauer, MD, ©2022 UpToDate, https://www.uptodate. com/contents/overview-of stem-cells, Literature review current through: Dec 2021. | This to- pic last updated: Jul 26, 2021.

Zakrzewski W, Dobrzyński M, Szymonowicz M, Rybak Z. Stem cells: past, present, and futu- re. Stem Cell Res Ther. 2019 Feb 26;10(1):68. doi: 10.1186/s13287-019-1165-5.

Douglas Melton, Chapter 2 - ‘Stemness’: Definitions, Criteria, and Standards, Editor(s): Ro- bert Lanza, Anthony Atala, Essentials of Stem Cell Biology (Third Edition), Pages 7-17, ISBN 9780124095038, https://doi.org/10.1016/B978-0-12-409503-8.00002-0. (https://www.scien- cedirect. com/science/article/pii/B9780124095038000020).

Kaya MM, Tutun H. Kök Hücre Üretimi, İzolasyonu ve Tedavide Kullanımı. Veteriner Farma- koloji ve Toksikoloji Derneği Bülteni, 2021;12(2):55-78. DOI: 10.38137/vftd.969798.

Kolios G, Moodley Y. Introduction to stem cells and regenerative medicine. Respiration. 2013;85(1):3-10. doi: 10.1159/000345615.

Kim SU,. Lee HJ. Human Neural Stem Cell-Based Cell- and Gene-Therapy for Neurological Diseases. In: Al-Rubeai, M., Naciri, M. (eds) Stem Cells and Cell Therapy. Cell Engineering, vol 8. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7196-3_2, 2014., pp.21-48. .

Sun JM, Kurtzberg J. Stem cell therapies in cerebral palsy and autism spectrum disorder. Dev Med Child Neurol. 2021 May;63(5):503-510. doi: 10.1111/dmcn.14789.

Alessandrini M, Preynat-Seauve O, De Bruin K, Pepper MS. Stem cell therapy for neurological disorders. S Afr Med J. 2019 Sep 10;109(8b):70-77. doi: 10.7196/SAMJ.2019.v109i8b.14009.

Romanov YA, Tarakanov OP, Radaev SM, Dugina TN, Ryaskina SS, Darevskaya AN, Mo- rozova YV, Khachatryan WA, Lebedev KE, Zotova NS, Burkova AS, Sukhikh GT, Smirnov VN. Human allogeneic AB0/Rh-identical umbilical cord blood cells in the treatment of juvenile patients with cerebral palsy. Cytotherapy. 2015 Jul;17(7):969-78. doi: 10.1016/j. jcyt.2015.02.010.

Jiao Y, Li XY, Liu J. A New Approach to Cerebral Palsy Treatment: Discussion of the Effective Components of Umbilical Cord Blood and its Mechanisms of Action. Cell Transplant. 2019 May;28(5):497-509. doi: 10.1177/0963689718809658.

Phuc PV, Ngoc VB, Lam DH, Tam NT, Viet PQ, Ngoc PK. Isolation of three important types of stem cells from the same samples of banked umbilical cord blood. Cell Tissue Bank. 2012 Jun;13(2):341-51. doi: 10.1007/s10561-011-9262-4.

McDonald CA, Fahey MC, Jenkin G, Miller SL. Umbilical cord blood cells for treatment of cerebral palsy; timing and treatment options. Pediatr Res. 2018 Jan;83(1-2):333-344. doi: 10.1038/pr.2017.236.

Novak I, Walker K, Hunt RW, Wallace EM, Fahey M, Badawi N. Concise Review: Stem Cell Interventions for People With Cerebral Palsy: Systematic Review With Meta-Analysis. Stem Cells Transl Med. 2016 Aug;5(8):1014-25. doi: 10.5966/sctm.2015-0372.

Rizk M, Aziz J, Shorr R, Allan DS. Cell-Based Therapy Using Umbilical Cord Blood for Novel Indications in Regenerative Therapy and Immune Modulation: An Updated Systematic Sco- ping Review of the Literature. Biol Blood Marrow Transplant. 2017 Oct;23(10):1607-1613. doi: 10.1016/j.bbmt.2017.05.032.

Forraz N, McGuckin CP. The umbilical cord: a rich and ethical stem cell source to advance regenerative medicine. Cell Prolif. 2011 Apr;44 Suppl 1(Suppl 1):60-9. doi: 10.1111/j.1365- 2184.2010.00729.x.

Matsumoto MM, Matthews KR. A Need for Renewed and Cohesive US Policy on Cord Blood Banking. Stem Cell Rev Rep. 2015 Dec;11(6):789-97. doi: 10.1007/s12015-015-9613-9.

Han MX, Craig ME. Research using autologous cord blood - time for a policy change. Med J Aust. 2013 Aug 19;199(4):288-99. doi: 10.5694/mja12.10835.

Finch-Edmondson M, Paton MCB, Webb A, Reza Ashrafi M, Blatch-Williams RK, Cox CS Jr, Crompton K, Griffin AR, Kim M, Kosmach S, Kurtzberg J, Nouri M, Ri Suh M, Sun J, Zarrabi M, Novak I. Cord Blood Treatment for Children With Cerebral Palsy: Individual Participant Data Meta-Analysis. Pediatrics. 2025 May 1;155(5):e2024068999. doi: 10.1542/ peds.2024-068999.

van de Ven C, Collins D, Bradley MB, Morris E, Cairo MS. The potential of umbilical cord blood multipotent stem cells for nonhematopoietic tissue and cell regeneration. Exp Hematol. 2007 Dec;35(12):1753-65. doi: 10.1016/j.exphem.2007.08.017.

Singer NG, Caplan AI. Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol. 2011;6:457-78. doi: 10.1146/annurev-pathol-011110-130230.

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Ke- ating A, Prockop Dj, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-7. doi: 10.1080/14653240600855905.

Siniscalco D, Sapone A, Cirillo A, Giordano C, Maione S, Antonucci N. Autism spectrum disorders: is mesenchymal stem cell personalized therapy the future? J Biomed Biotechnol. 2012;2012:480289. doi: 10.1155/2012/480289.

Siniscalco D, Giordano C, Galderisi U, Luongo L, Alessio N, Di Bernardo G, de Novellis V, Rossi F, Maione S. Intra-brain microinjection of human mesenchymal stem cells decreases allodynia in neuropathic mice. Cell Mol Life Sci. 2010 Feb;67(4):655-69. doi: 10.1007/s00018- 009-0202-4.

Bianco P. “Mesenchymal” stem cells. Annu Rev Cell Dev Biol. 2014;30:677-704. doi: 10.1146/ annurev-cellbio-100913-013132.

Obtulowicz P, Lech W, Strojek L, Sarnowska A, Domanska-Janik K. Induction of Endothelial Phenotype From Wharton’s Jelly-Derived MSCs and Comparison of Their Vasoprotective and Neuroprotective Potential With Primary WJ-MSCs in CA1 Hippocampal Region Ex Vivo. Cell Transplant. 2016;25(4):715-27. doi: 10.3727/096368915X690369.

Lv FJ, Tuan RS, Cheung KM, Leung VY. Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells. 2014 Jun;32(6):1408-19. doi: 10.1002/stem.1681.

Gönen BZ, Gökdemir NS. Mezenkimal Kök Hücreler ve Klinik Kullanımı. In, Canpolat, Ço- cuk Nörolojisi Pratiğinde Kök Hücre Multidisipliner Yaklaşım (Editör: Canpolat M). Akade- misyen Kitabevi, Ankara, ISBN:9786253994099, 2023. pp.117-125.

Griffin MD, Elliman SJ, Cahill E, English K, Ceredig R, Ritter T. Concise review: adult mesen- chymal stromal cell therapy for inflammatory diseases: how well are we joining the dots? Stem Cells. 2013 Oct;31(10):2033-41. doi: 10.1002/stem.1452.

Newman RE, Yoo D, LeRoux MA, Danilkovitch-Miagkova A. Treatment of inflammatory diseases with mesenchymal stem cells. Inflamm Allergy Drug Targets. 2009 Jun;8(2):110-23. doi: 10.2174/187152809788462635.

Siniscalco D, Kannan S, Semprún-Hernández N, Eshraghi AA, Brigida AL, Antonucci N. Stem cell therapy in autism: recent insights. Stem Cells Cloning. 2018 Oct 23;11:55-67. doi: 10.2147/SCCAA.S155410.

Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Stewart DJ; Canadian Critical Care Trials Group. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012;7(10):e47559. doi: 10.1371/journal.pone.0047559.

Doğan A. Embryonic Stem Cells in Development and Regenerative Medicine. Adv Exp Med Biol. 2018;1079:1-15. doi: 10.1007/5584_2018_175.

Hsu YC, Lee DC, Chiu IM. Neural stem cells, neural progenitors, and neurotrophic factors. Cell Transplant. 2007;16(2):133-50.

Santilli G, Lamorte G, Carlessi L, Ferrari D, Rota Nodari L, Binda E, Delia D, Vescovi AL, De Filippis L. Mild hypoxia enhances proliferation and multipotency of human neural stem cells. PLoS One. 2010 Jan 5;5(1):e8575. doi: 10.1371/journal.pone.0008575.

Ardhanareeswaran K, Coppola G, Vaccarino F. The use of stem cells to study autism spectrum disorder. Yale J Biol Med. 2015 Mar 4;88(1):5-16.

Szabłowska-Gadomska I, Bużańska L, Małecki M. Stem cell properties, current le- gal status and medical application. Postepy Hig. Med. Dosw. 2017;71:1216–1230. doi: 10.5604/01.3001.0010.7733.

Brigida AL, Siniscalco D. Induced pluripotent stem cells as a cellular model for studying Down Syndrome. J Stem Cells Regen Med. 2016 Nov 29;12(2):54-60. doi: 10.46582/jsrm.1202009.

Augustyniak J, Zychowicz M, Podobinska M, Barta T, Buzanska L. Reprogramming of soma- tic cells: possible methods to derive safe, clinical-grade human induced pluripotent stem cells. Acta Neurobiol Exp (Wars). 2014;74(4):373-82. doi: 10.55782/ane-2014-2000.

Rao MS, Malik N. Assessing iPSC reprogramming methods for their suitability in translatio- nal medicine. J Cell Biochem. 2012 Oct;113(10):3061-8. doi: 10.1002/jcb.24183.

Nori S, Okada Y, Nishimura S, Sasaki T, Itakura G, Kobayashi Y, Renault-Mihara F, Shimizu A, Koya I, Yoshida R, Kudoh J, Koike M, Uchiyama Y, Ikeda E, Toyama Y, Nakamura M, Okano H. Long-term safety issues of iPSC-based cell therapy in a spinal cord injury model: oncogenic transformation with epithelial-mesenchymal transition. Stem Cell Reports. 2015 Mar 10;4(3):360-73. doi: 10.1016/j.stemcr.2015.01.006.

Attwood SW, Edel MJ. iPS-Cell Technology and the Problem of Genetic Instability-Can It Ever Be Safe for Clinical Use? J Clin Med. 2019 Feb 28;8(3):288. doi: 10.3390/jcm8030288.

Linda K, Fiuza C, Nadif Kasri N. The promise of induced pluripotent stem cells for neurodevelopmental disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jun 8;84(Pt B):382-391. doi: 10.1016/j.pnpbp.2017.11.009.

Alessio N, Brigida AL, Peluso G, Antonucci N, Galderisi U, Siniscalco D. Stem Cell-De- rived Exosomes in Autism Spectrum Disorder. Int J Environ Res Public Health. 2020 Feb 4;17(3):944. doi: 10.3390/ijerph17030944.

Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. Vesicle formation during reticu- locyte maturation. Association of plasma membrane activities with released vesicles (exoso- mes). J Biol Chem. 1987 Jul 5;262(19):9412-20.

Borges FT, Reis LA, Schor N. Extracellular vesicles: structure, function, and potential clini- cal uses in renal diseases. Braz J Med Biol Res. 2013 Oct;46(10):824-30. doi: 10.1590/1414- 431X20132964.

Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. Mini- mal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guide- lines. J Extracell Vesicles. 2018 Nov 23;7(1):1535750. doi: 10.1080/20013078.2018.1535750.

Harrell CR, Volarevic A, Djonov V, Volarevic V. Mesenchymal Stem Cell-Derived Exoso- mes as New Remedy for the Treatment of Neurocognitive Disorders. Int J Mol Sci. 2021 Feb 1;22(3):1433. doi: 10.3390/ijms22031433.

Darwish M, El Hajj R, Khayat L, Alaaeddine N. Stem Cell Secretions as a Potential Thera- peutic Agent for Autism Spectrum Disorder: A Narrative Review. Stem Cell Rev Rep. 2024 Jul;20(5):1252-1272. doi: 10.1007/s12015-024-10724-4.

Kathuria A, Nowosiad P, Jagasia R, Aigner S, Taylor RD, Andreae LC, Gatford NJF, Lucchesi W, Srivastava DP, Price J. Stem cell-derived neurons from autistic individuals with SHANK3 mutation show morphogenetic abnormalities during early development. Mol Psychiatry. 2018 Mar;23(3):735-746. doi: 10.1038/mp.2017.185.

Nestor MW, Phillips AW, Artimovich E, Nestor JE, Hussman JP, Blatt GJ. Human Inducible Pluripotent Stem Cells and Autism Spectrum Disorder: Emerging Technologies. Autism Res. 2016 May;9(5):513-35. doi: 10.1002/aur.1570.

Tania M, Khan MA, Xia K. Recent advances in animal model experimentation in autism rese- arch. Acta Neuropsychiatr. 2014 Oct;26(5):264-71. doi: 10.1017/neu.2013.58.

Segal-Gavish H, Karvat G, Barak N, Barzilay R, Ganz J, Edry L, Aharony I, Offen D, Kimchi

T. Mesenchymal Stem Cell Transplantation Promotes Neurogenesis and Ameliorates Autism Related Behaviors in BTBR Mice. Autism Res. 2016 Jan;9(1):17-32. doi: 10.1002/aur.1530.

Perets N, Segal-Gavish H, Gothelf Y, Barzilay R, Barhum Y, Abramov N, Hertz S, Morozov D, London M, Offen D. Long term beneficial effect of neurotrophic factors-secreting mesenchy- mal stem cells transplantation in the BTBR mouse model of autism. Behav Brain Res. 2017 Jul 28;331:254-260. doi: 10.1016/j.bbr.2017.03.047.

Ha S, Park H, Mahmood U, Ra JC, Suh YH, Chang KA. Human adipose-derived stem cells ameliorate repetitive behavior, social deficit and anxiety in a VPA-induced autism mouse mo- del. Behav Brain Res. 2017 Jan 15;317:479-484. doi: 10.1016/j.bbr.2016.10.004.

Gobshtis N, Tfilin M, Wolfson M, Fraifeld VE, Turgeman G. Transplantation of mesenchy- mal stem cells reverses behavioural deficits and impaired neurogenesis caused by prenatal exposure to valproic acid. Oncotarget. 2017 Mar 14;8(11):17443-17452. doi: 10.18632/onco- target.15245.

Hsiao EY, McBride SW, Chow J, Mazmanian SK, Patterson PH. Modeling an autism risk fa- ctor in mice leads to permanent immune dysregulation. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12776-81. doi: 10.1073/pnas.1202556109.

Weick JP, Liu Y, Zhang SC. Human embryonic stem cell-derived neurons adopt and re- gulate the activity of an established neural network. Proc Natl Acad Sci U S A. 2011 Dec13;108(50):20189-94. doi: 10.1073/pnas.1108487108.

Höing S, Rudhard Y, Reinhardt P, Glatza M, Stehling M, Wu G, Peiker C, Böcker A, Parga JA, Bunk E, Schwamborn JC, Slack M, Sterneckert J, Schöler HR. Discovery of inhibitors of microglial neurotoxicity acting through multiple mechanisms using a stem-cell-based pheno- typic assay. Cell Stem Cell. 2012 Nov 2;11(5):620-32. doi: 10.1016/j.stem.2012.07.005.

Kaya M, Karasalihoğlu S, Ustün F, Gültekin A, Cermik TF, Fazlioğlu Y, Türe M, Yiğitbaşi ON, Berkarda S. The relationship between 99mTc-HMPAO brain SPECT and the scores of real life rating scale in autistic children. Brain Dev. 2002 Mar;24(2):77-81. doi: 10.1016/s0387- 7604(02)00006-2.

Calió ML, Marinho DS, Ko GM, Ribeiro RR, Carbonel AF, Oyama LM, Ormanji M, Gui- rao TP, Calió PL, Reis LA, Simões Mde J, Lisbôa-Nascimento T, Ferreira AT, Bertoncini CR. Transplantation of bone marrow mesenchymal stem cells decreases oxidative stress, apopto- sis, and hippocampal damage in brain of a spontaneous stroke model. Free Radic Biol Med. 2014 May;70:141-54. doi: 10.1016/j.freeradbiomed.2014.01.024.

Wada N, Gronthos S, Bartold PM. Immunomodulatory effects of stem cells. Periodontol 2000. 2013 Oct;63(1):198-216. doi: 10.1111/prd.12024.

Siniscalco D, Bradstreet JJ, Sych N, Antonucci N. Perspectives on the use of stem cells for autism treatment. Stem Cells Int. 2013;2013:262438. doi: 10.1155/2013/262438.

Gesundheit B, Ashwood P, Keating A, Naor D, Melamed M, Rosenzweig JP. Therapeutic pro- perties of mesenchymal stem cells for autism spectrum disorders. Med Hypotheses. 2015 Mar;84(3):169-77. doi: 10.1016/j.mehy.2014.12.016.

Jaimes Y, Naaldijk Y, Wenk K, Leovsky C, Emmrich F. Mesenchymal Stem Cell-Derived Mic- rovesicles Modulate Lipopolysaccharides-Induced Inflammatory Responses to Microglia Cel- ls. Stem Cells. 2017 Mar;35(3):812-823. doi: 10.1002/stem.2541.

Ooi YY, Dheen ST, Tay SS. Paracrine effects of mesenchymal stem cells-conditioned medium on microglial cytokines expression and nitric oxide production. Neuroimmunomodulation. 2015;22(4):233-42. doi: 10.1159/000365483.

Nguyen Thanh L, Nguyen HP, Ngo MD, Bui VA, Dam PTM, Bui HTP, Ngo DV, Tran KT, Dang TTT, Duong BD, Nguyen PAT, Forsyth N, Heke M. Outcomes of bone marrow mo- nonuclear cell transplantation combined with interventional education for autism spectrum disorder. Stem Cells Transl Med. 2021 Jan;10(1):14-26. doi: 10.1002/sctm.20-0102. Epub 2020 Sep 9. Erratum in: Stem Cells Transl Med. 2021 Dec;10(12):1721. doi: 10.1002/sct3.13043.

Sharma A, Gokulchandran N, Sane H, Nagrajan A, Paranjape A, Kulkarni P, Shetty A, Mishra P, Kali M, Biju H, Badhe P. Autologous bone marrow mononuclear cell therapy for autism: an open label proof of concept study. Stem Cells Int. 2013;2013:623875. doi: 10.1155/2013/623875.

Dawson G, Sun JM, Davlantis KS, Murias M, Franz L, Troy J, Simmons R, Sabatos-DeVito M, Durham R, Kurtzberg J. Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open-Label Trial. Stem Cells Transl Med. 2017 May;6(5):1332-1339. doi: 10.1002/sctm.16-0474.

Dawson G, Sun JM, Baker J, Carpenter K, Compton S, Deaver M, Franz L, Heilbron N, Herold B, Horrigan J, Howard J, Kosinski A, Major S, Murias M, Page K, Prasad VK, Sabatos-DeVito M, Sanfilippo F, Sikich L, Simmons R, Song A, Vermeer S, Waters-Pick B, Troy J, Kurtzberg

J. A Phase II Randomized Clinical Trial of the Safety and Efficacy of Intravenous Umbilical Cord Blood Infusion for Treatment of Children with Autism Spectrum Disorder. J Pediatr. 2020 Jul;222:164-173.e5. doi: 10.1016/j.jpeds.2020.03.011.

Lv YT, Zhang Y, Liu M, Qiuwaxi JN, Ashwood P, Cho SC, Huan Y, Ge RC, Chen XW, Wang ZJ, Kim BJ, Hu X. Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. J Transl Med. 2013 Aug 27;11:196. doi: 10.1186/1479-5876-11-196.

Liu Q, Chen MX, Sun L, Wallis CU, Zhou JS, Ao LJ, Li Q, Sham PC. Rational use of mesench- ymal stem cells in the treatment of autism spectrum disorders. World J Stem Cells. 2019 Feb 26;11(2):55-72. doi: 10.4252/wjsc.v11.i2.55.

Qu J, Liu Z, Li L, Zou Z, He Z, Zhou L, Luo Y, Zhang M, Ye J. Efficacy and Safety of Stem Cell Therapy in Children With Autism Spectrum Disorders: A Systematic Review and Meta-A- nalysis. Front Pediatr. 2022 May 4;10:897398. doi: 10.3389/fped.2022.897398.

Stancioiu FA, Bogdan R, Ivanescu B, Dumitrescu R. Autologous cord blood vs individualized supplements in autistic spectrum disorder: CORDUS study results. World J Clin Pediatr. 2025 Mar 9;14(1):96643. doi: 10.5409/wjcp.v14.i1.96643.

Kabatas S, Civelek E, Savrunlu EC, Karaaslan U, Yıldız Ö, Karaöz E. Advances in the treat- ment of autism spectrum disorder: Wharton jelly mesenchymal stem cell transplantation. World J Methodol. 2025 Mar 20;15(1):95857. doi: 10.5662/wjm.v15.i1.95857.

Guillot PV, Gotherstrom C, Chan J, Kurata H, Fisk NM. Human first-trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC. Stem Cells. 2007 Mar;25(3):646-54. doi: 10.1634/stemcells.2006-0208.

Lee H, Yun S, Kim IS, Lee IS, Shin JE, Park SC, Kim WJ, Park KI. Human fetal brain-deri- ved neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy. PLoS One. 2014 Aug 8;9(8):e104092. doi: 10.1371/journal. pone.0104092.

Kelly S, Bliss TM, Shah AK, Sun GH, Ma M, Foo WC, Masel J, Yenari MA, Weissman IL, Uchida N, Palmer T, Steinberg GK. Transplanted human fetal neural stem cells survive, mig- rate, and differentiate in ischemic rat cerebral cortex. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11839-44. doi: 10.1073/pnas.0404474101.

Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med. 2001 Mar 8;344(10):710-9. doi: 10.1056/ NEJM200103083441002.

Bradstreet JJ, Sych N, Antonucci N, Klunnik M, Ivankova O, Matyashchuk I, Demchuk M, Si- niscalco D. Efficacy of fetal stem cell transplantation in autism spectrum disorders: an open-la- beled pilot study. Cell Transplant. 2014;23 Suppl 1:S105-112. doi: 10.3727/096368914X684916.

Kassis I, Vaknin-Dembinsky A, Karussis D. Bone marrow mesenchymal stem cells: agents of immunomodulation and neuroprotection. Curr Stem Cell Res Ther. 2011 Mar;6(1):63-8. doi: 10.2174/157488811794480762.

Klyushnenkova E, Mosca JD, Zernetkina V, Majumdar MK, Beggs KJ, Simonetti DW, Deans RJ, McIntosh KR. T cell responses to allogeneic human mesenchymal stem cells: immunoge- nicity, tolerance, and suppression. J Biomed Sci. 2005;12(1):47-57. doi: 10.1007/s11373-004- 8183-7.

Jacobs SA, Roobrouck VD, Verfaillie CM, Van Gool SW. Immunological characteristics of human mesenchymal stem cells and multipotent adult progenitor cells. Immunol Cell Biol. 2013 Jan;91(1):32-9. doi: 10.1038/icb.2012.64.

Karussis D, Petrou P, Kassis I. Clinical experience with stem cells and other cell therapies in neurological diseases. J Neurol Sci. 2013 Jan 15;324(1-2):1-9. doi: 10.1016/j.jns.2012.09.031.

Ding DC, Chang YH, Shyu WC, Lin SZ. Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy. Cell Transplant. 2015;24(3):339-47. doi: 10.3727/096368915X686841.

Xu Y, Huang S, Ma K, Fu X, Han W, Sheng Z. Promising new potential for mesenchymal stem cells derived from human umbilical cord Wharton’s jelly: sweat gland cell-like differentiative capacity. J Tissue Eng Regen Med. 2012 Aug;6(8):645-54. doi: 10.1002/term.468.

Alessio N, Pipino C, Mandatori D, Di Tomo P, Ferone A, Marchiso M, Melone MAB, Peluso G, Pandolfi A, Galderisi U. Mesenchymal stromal cells from amniotic fluid are less prone to senescence compared to those obtained from bone marrow: An in vitro study. J Cell Physiol. 2018 Nov;233(11):8996-9006. doi: 10.1002/jcp.26845.

Witkowska-Zimny M, Wrobel E. Perinatal sources of mesenchymal stem cells: Wharton’s jelly, amnion and chorion. Cell Mol Biol Lett. 2011 Sep;16(3):493-514. doi: 10.2478/s11658- 011-0019-7.

Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, Yos- himura K, Gimble JM. Stromal cells from the adipose tissue-derived stromal vascular fracti- on and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the Internatio- nal Society for Cellular Therapy (ISCT). Cytotherapy. 2013 Jun;15(6):641-8. doi: 10.1016/j. jcyt.2013.02.006.

Frese L, Dijkman PE, Hoerstrup SP. Adipose Tissue-Derived Stem Cells in Regenerative Me- dicine. Transfus Med Hemother. 2016 Jul;43(4):268-274. doi: 10.1159/000448180.

Zhou F, Gao S, Wang L, Sun C, Chen L, Yuan P, Zhao H, Yi Y, Qin Y, Dong Z, Cao L, Ren H, Zhu L, Li Q, Lu B, Liang A, Xu GT, Zhu H, Gao Z, Ma J, Xu J, Chen X. Human adipose-derived stem cells partially rescue the stroke syndromes by promoting spatial learning and memory in mouse middle cerebral artery occlusion model. Stem Cell Res Ther. 2015 May 9;6(1):92. doi: 10.1186/s13287-015-0078-1. Erratum in: Stem Cell Res Ther. 2019 Mar 6;10(1):76. doi: 10.1186/s13287-019-1198-9.

Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006 Aug 25;126(4):663-76. doi: 10.1016/j. cell.2006.07.024.

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 Nov 30;131(5):861-72. doi: 10.1016/j.cell.2007.11.019.

Medvedev SP, Shevchenko AI, Zakian SM. Induced Pluripotent Stem Cells: Problems and Ad- vantages when Applying them in Regenerative Medicine. Acta Naturae. 2010 Jul;2(2):18-28.

Sharma AK, Gokulchandran N, Kulkarni PP, Sane HM, Sharma R, Jose A, Badhe PB. Cell transplantation as a novel therapeutic strategy for autism spectrum disorders: a clinical study. Am J Stem Cells. 2020 Dec 25;9(5):89-100.

Chez M, Lepage C, Parise C, Dang-Chu A, Hankins A, Carroll M. Safety and Observations from a Placebo-Controlled, Crossover Study to Assess Use of Autologous Umbilical Cord Blood Stem Cells to Improve Symptoms in Children with Autism. Stem Cells Transl Med. 2018 Apr;7(4):333-341. doi: 10.1002/sctm.17-0042.

Li Q, Chen CF, Wang DY, Lü YT, Huan Y, Fang SX, Han Y, Ge RC, Chen XW. Changes in growth factor levels in the cerebrospinal fluid of autism patients after transplantation of hu- man umbilical cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells. Genet Mol Res. 2016 May 23;15(2). doi: 10.4238/gmr.15027526. Retraction in: Genet Mol Res. 2016 Oct 7;15(4). doi: 10.4238/gmr.1504004.

Sun JM, Kurtzberg J. Cell therapy for diverse central nervous system disorders: inherited me- tabolic diseases and autism. Pediatr Res. 2018 Jan;83(1-2):364-371. doi: 10.1038/pr.2017.254.

Villarreal-Martínez L, González-Martínez G, Sáenz-Flores M, Bautista-Gómez AJ, Gonzá- lez-Martínez A, Ortiz-Castillo M, Robles-Sáenz DA, Garza-López E. Stem Cell Therapy in the Treatment of Patients With Autism Spectrum Disorder: a Systematic Review and Meta-analy- sis. Stem Cell Rev Rep. 2022 Jan;18(1):155-164. doi: 10.1007/s12015-021-10257-0.

Murias M, Major S, Compton S, Buttinger J, Sun JM, Kurtzberg J, Dawson G. Electrophysio- logical Biomarkers Predict Clinical Improvement in an Open-Label Trial Assessing Efficacy of Autologous Umbilical Cord Blood for Treatment of Autism. Stem Cells Transl Med. 2018 Nov;7(11):783-791. doi: 10.1002/sctm.18-0090.

Nguyen LT, Nguyen PM, Nguyen HP, Bui HT, Dao LTM, Van Pham M, Hoang CK, Nguyen PT, Nguyen TTP, Nguyen ATP, Hoang VT, Bui HTP, Vuong NK, Van Ngo D. Outcomes of autologous bone marrow mononuclear cell administration combined with educational inter- vention in the treatment of autism spectrum disorder: a randomized, open-label, controlled phase II clinical trial. Stem Cell Res Ther. 2025 May 30;16(1):268. doi: 10.1186/s13287-025- 04404-4.

Kimberly LH. Carpenter, Samantha Major, Catherine Tallman, Lyon W. Chen, Lauren Franz, Jessica Sun, Joanne Kurtzberg, Allen Song, Geraldine Dawson, White Matter Tract Changes Associated with Clinical Improvement in an Open-Label Trial Assessing Autologous Umbili- cal Cord Blood for Treatment of Young Children with Autism, Stem Cells Translational Medi- cine, Volume 8, Issue 2, February 2019, Pages 138–147, https://doi.org/10.1002/sctm.18-0251

Wong CM, Tan CS, Riard N, Padmini YS, Daniel LM, Prasath A, Tan AM, Tan TC, Sultana R, Lam JCM. Autologous umbilical cord blood infusion for the treatment of autism in young children: A within-subjects open label study on safety (assessed via caregiver report) and efficacy. Autism Res. 2024 Aug;17(8):1721-1734. doi: 10.1002/aur.3187.

Riordan NH, Hincapié ML, Morales I, Fernández G, Allen N, Leu C, Madrigal M, Paz Rodrí- guez J, Novarro N. Allogeneic Human Umbilical Cord Mesenchymal Stem Cells for the Treat- ment of Autism Spectrum Disorder in Children: Safety Profile and Effect on Cytokine Levels. Stem Cells Transl Med. 2019 Oct;8(10):1008-1016. doi: 10.1002/sctm.19-0010. Epub 2019 Jun

11. Retraction in: Stem Cells Transl Med. 2021 Dec;10(12):1717. doi: 10.1002/sct3.13044.

Adnan M, Motiwala F, Trivedi C, Chaudhari G, Mansuri Z, Jain S. Human Umbilical Cord Blood Infusions in the Management of Autism Spectrum Disorder. Prim Care Companion CNS Disord. 2022 Jun 2;24(3):21r03042. doi: 10.4088/PCC.21r03042.

Carpenter KLH, Major S, Tallman C, Chen LW, Franz L, Sun J, Kurtzberg J, Song A, Dawson

G. White Matter Tract Changes Associated with Clinical Improvement in an Open-Label Tri- al Assessing Autologous Umbilical Cord Blood for Treatment of Young Children with Autism. Stem Cells Transl Med. 2019 Feb;8(2):138-147. doi: 10.1002/sctm.18-0251.

Michael Murias, Samantha Major, Scott Compton, Jessica Buttinger, Jessica M. Sun, Joan- ne Kurtzberg, Geraldine Dawson, Electrophysiological Biomarkers Predict Clinical Impro- vement in an Open-Label Trial Assessing Efficacy of Autologous Umbilical Cord Blood for Treatment of Autism, Stem Cells Translational Medicine, Volume 7, Issue 11, November 2018, Pages 783–791, https://doi.org/10.1002/sctm.18-0090

Sharifzadeh N, Ghasemi A, Tavakol Afshari J, Moharari F, Soltanifar A, Talaei A, Pouryousof HR, Nahidi M, Fayyazi Bordbar MR, Ziaee M. Intrathecal autologous bone marrow stem cell therapy in children with autism: A randomized controlled trial. Asia Pac Psychiatry. 2021 Jun;13(2):e12445. doi: 10.1111/appy.12445.

Hughes HK, R J Moreno, Ashwood P. Innate immune dysfunction and neuroinflammation in autism spectrum disorder (ASD). Brain Behav Immun. 2023 Feb;108:245-254. doi: 10.1016/j. bbi.2022.12.001.

Sun JM, Dawson G, Franz L, Howard J, McLaughlin C, Kistler B, Waters-Pick B, Meadows N, Troy J, Kurtzberg J. Infusion of human umbilical cord tissue mesenchymal stromal cells in children with autism spectrum disorder. Stem Cells Transl Med. 2020 Oct;9(10):1137-1146. doi: 10.1002/sctm.19-0434.

Shabab T, Khanabdali R, Moghadamtousi SZ, Kadir HA, Mohan G. Neuroinflam- mation pathways: a general review. Int J Neurosci. 2017 Jul;127(7):624-633. doi: 10.1080/00207454.2016.1212854.

Inga Jácome MC, Morales Chacòn LM, Vera Cuesta H, Maragoto Rizo C, Whilby Santieste- ban M, Ramos Hernandez L, Noris García E, González Fraguela ME, Fernandez Verdecia CI, Vegas Hurtado Y, et al. Peripheral Inflammatory Markers Contributing to Comorbidities in Autism. Behavioral Sciences. 2016; 6(4):29. https://doi.org/10.3390/bs6040029

Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005 Jan;57(1):67- 81. doi: 10.1002/ana.20315. Erratum in: Ann Neurol. 2005 Feb;57(2):304.

Goines PE, Ashwood P. Cytokine dysregulation in autism spectrum disorders (ASD): pos- sible role of the environment. Neurotoxicol Teratol. 2013 Mar-Apr;36:67-81. doi: 10.1016/j. ntt.2012.07.006.

Cianciulli A, Porro C, Calvello R, Trotta T, Lofrumento DD, Panaro MA. Microglia Mediated Neuroinflammation: Focus on PI3K Modulation. Biomolecules. 2020 Jan 14;10(1):137. doi: 10.3390/biom10010137.

Ashwood P, Anthony A, Torrente F, Wakefield AJ. Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: mucosal immune activation and reduced counter regulatory interleukin-10. J Clin Immunol. 2004 Nov;24(6):664-73. doi: 10.1007/s10875-004-6241-6.

Liao X, Liu Y, Fu X, Li Y. Postmortem Studies of Neuroinflammation in Autism Spectrum Di- sorder: a Systematic Review. Mol Neurobiol. 2020 Aug;57(8):3424-3438. doi: 10.1007/s12035- 020-01976-5.

Masi A, Breen EJ, Alvares GA, Glozier N, Hickie IB, Hunt A, Hui J, Beilby J, Ravine D, Wray J, Whitehouse AJO, Guastella AJ. Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder. Mol Autism. 2017 Dec 2;8:63. doi: 10.1186/s13229-017-0176-2.

Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun. 2011 Jan;25(1):40-5. doi: 10.1016/j.bbi.2010.08.003.

Wei H, Chadman KK, McCloskey DP, Sheikh AM, Malik M, Brown WT, Li X. Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. Biochim Biophys Acta. 2012 Jun;1822(6):831-42. doi: 10.1016/j.bbadis.2012.01.011.

Meyer U. Prenatal poly(i:C) exposure and other developmental immune activation mo- dels in rodent systems. Biol Psychiatry. 2014 Feb 15;75(4):307-15. doi: 10.1016/j.biopsy- ch.2013.07.011.

Choi GB, Yim YS, Wong H, Kim S, Kim H, Kim SV, Hoeffer CA, Littman DR, Huh JR. The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science. 2016 Feb 26;351(6276):933-9. doi: 10.1126/science.aad0314.

Lucchina L, Depino AM. Altered peripheral and central inflammatory responses in a mouse model of autism. Autism Res. 2014 Apr;7(2):273-89. doi: 10.1002/aur.1338.

Heo Y, Zhang Y, Gao D, Miller VM, Lawrence DA. Aberrant immune responses in a mouse with behavioral disorders. PLoS One. 2011;6(7):e20912. doi: 10.1371/journal.pone.0020912.

Rose S, Melnyk S, Pavliv O, Bai S, Nick TG, Frye RE, James SJ. Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry. 2012 Jul 10;2(7):e134. doi: 10.1038/tp.2012.61.

Siddiqui MF, Elwell C, Johnson MH. Mitochondrial Dysfunction in Autism Spectrum Di- sorders. Autism Open Access. 2016 Sep 27;6(5):1000190. doi: 10.4172/2165-7890.1000190.

Kumar S, Verma R, Tyagi N, Gangenahalli G, Verma YK. Therapeutics effect of mesenchymal stromal cells in reactive oxygen species-induced damages. Hum Cell. 2022 Jan;35(1):37-50. doi: 10.1007/s13577-021-00646-5.

Shea S, Turgay A, Carroll A, Schulz M, Orlik H, Smith I, Dunbar F. Risperidone in the tre- atment of disruptive behavioral symptoms in children with autistic and other pervasive de- velopmental disorders. Pediatrics. 2004 Nov;114(5):e634-41. doi: 10.1542/peds.2003-0264-F.

Owen R, Sikich L, Marcus RN, Corey-Lisle P, Manos G, McQuade RD, Carson WH, Findling RL. Aripiprazole in the treatment of irritability in children and adolescents with autistic di- sorder. Pediatrics. 2009 Dec;124(6):1533-40. doi: 10.1542/peds.2008-3782.

Sharma SR, Gonda X, Tarazi FI. Autism Spectrum Disorder: Classification, diagnosis and therapy. Pharmacol Ther. 2018 Oct;190:91-104. doi: 10.1016/j.pharmthera.2018.05.007.

Park SR, Kim JW, Jun HS, Roh JY, Lee HY, Hong IS. Stem Cell Secretome and Its Effect on Cellular Mechanisms Relevant to Wound Healing. Mol Ther. 2018 Feb 7;26(2):606-617. doi: 10.1016/j.ymthe.2017.09.023.

Araújo, B., Silva, R.C., Domingues, S., Salgado, A.J., Teixeira, F.G. Mesenchymal Stem Cell Secretome: A Potential Biopharmaceutical Component to Regenerative Medicine?. In: Hai- der, K.H. (eds) Handbook of Stem Cell Therapy. Springer, Singapore. 2022, pp. 1-33, https:// doi.org/10.1007/978-981-16-6016-0_46-1

Md Fadilah NI, Mohd Abdul Kader Jailani MS, Badrul Hisham MAI, Sunthar Raj N, Sham- suddin SA, Ng MH, Fauzi MB, Maarof M. Cell secretomes for wound healing and tissue rege- neration: Next generation acellular based tissue engineered products. J Tissue Eng. 2022 Jul 28;13:20417314221114273. doi: 10.1177/20417314221114273.

Blatt GJ. The neuropathology of autism. Scientifica (Cairo). 2012;2012:703675. doi: 10.6064/2012/703675.

Reiersen AM, Todd RD. Co-occurrence of ADHD and autism spectrum disorders: phenomenology and treatment. Expert Rev Neurother. 2008 Apr;8(4):657-69. doi: 10.1586/14737175.8.4.657.

Kang X, Zuo Z, Hong W, Tang H, Geng W. Progress of Research on Exosomes in the Pro- tection Against Ischemic Brain Injury. Front Neurosci. 2019 Oct 29;13:1149. doi: 10.3389/ fnins.2019.01149.

Li Q, Wang H, Peng H, Huyan T, Cacalano NA. Exosomes: Versatile Nano Mediators of Im- mune Regulation. Cancers (Basel). 2019 Oct 14;11(10):1557. doi: 10.3390/cancers11101557.

Geffen Y., Perets N., Horev R., Yudin D., Oron O., Elliott E., Marom E., Danon U., Offen D.Exosomes derived from adipose mesenchymal stem cells: a potential non-invasive intra- nasal treatment for autism, Cytotherapy, Volume 22, Issue 5, Supplement, 2020, Page S49, ISSN 1465-3249, https://doi.org/10.1016/j.jcyt.2020.03.059. (https://www.sciencedirect.com/ science/article/pii/S1465324920301237)

Hanson LR, Frey WH 2nd. Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease. BMC Neurosci. 2008 Dec 10;9 Suppl 3(Suppl 3):S5. doi: 10.1186/1471-2202-9-S3-S5.

Chavez B, Chavez-Brown M, Rey JA. Role of risperidone in children with autism spectrum disorder. Ann Pharmacother. 2006 May;40(5):909-16. doi: 10.1345/aph.1G389.

Liang Y, Duan L, Xu X, Li X, Liu M, Chen H, Lu J, Xia J. Mesenchymal Stem Cell-Deri- ved Exosomes for Treatment of Autism Spectrum Disorder. ACS Appl Bio Mater. 2020 Sep 21;3(9):6384-6393. doi: 10.1021/acsabm.0c00831.

Zhang X, Liu T, Hou X, Zhou Z, Zhang F, Ma H, Wu X, Jiang J. Exosomes secreted by me- senchymal stem cells delay brain aging by upregulating SIRT1 expression. Sci Rep. 2023 Aug 14;13(1):13213. doi: 10.1038/s41598-023-40543-5.

Heo JS, Choi Y, Kim HO. Adipose-Derived Mesenchymal Stem Cells Promote M2 Mac- rophage Phenotype through Exosomes. Stem Cells Int. 2019 Nov 5;2019:7921760. doi: 10.1155/2019/7921760.

Perets N, Betzer O, Shapira R, Brenstein S, Angel A, Sadan T, Ashery U, Popovtzer R, Offen

D. Golden Exosomes Selectively Target Brain Pathologies in Neurodegenerative and Neuro- developmental Disorders. Nano Lett. 2019 Jun 12;19(6):3422-3431. doi: 10.1021/acs.nano- lett.8b04148.

Hashem S, Nisar S, Bhat AA, Yadav SK, Azeem MW, Bagga P, Fakhro K, Reddy R, Frenneaux MP, Haris M. Genetics of structural and functional brain changes in autism spectrum disor- der. Transl Psychiatry. 2020 Jul 13;10(1):229. doi: 10.1038/s41398-020-00921-3.

Perets N, Oron O, Herman S, Elliott E, Offen D. Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B. Mol Autism. 2020 Aug 17;11(1):65. doi: 10.1186/s13229-020-00366-x.

Siniscalco D, Cirillo A, Bradstreet JJ, Antonucci N. Epigenetic findings in autism: new perspe- ctives for therapy. Int J Environ Res Public Health. 2013 Sep 11;10(9):4261-73. doi: 10.3390/ ijerph10094261.

Stankovic I, Smit P, Cross J, Wolujewicz P, Greening D, Colak D. Extracellular Vesicle Profiling Reveals Novel Autism Signatures in Patient-Derived Forebrain Organoids. Res Sq [Preprint]. 2025 May 13:rs.3.rs-6573757. doi: 10.21203/rs.3.rs-6573757/v1. Update in: Transl Psychiatry. 2025 Oct 10;15(1):393. doi: 10.1038/s41398-025-03607-w.

Sharma P, Mesci P, Carromeu C, McClatchy DR, Schiapparelli L, Yates JR 3rd, Muotri AR, Cline HT. Exosomes regulate neurogenesis and circuit assembly. Proc Natl Acad Sci U S A. 2019 Aug 6;116(32):16086-16094. doi: 10.1073/pnas.1902513116.

Squillaro T, Hayek G, Farina E, Cipollaro M, Renieri A, Galderisi U. A case report: bone marrow mesenchymal stem cells from a Rett syndrome patient are prone to senescence and show a lower degree of apoptosis. J Cell Biochem. 2008 Apr 15;103(6):1877-85. doi: 10.1002/ jcb.21582.

Gottfried C, Bambini-Junior V, Francis F, Riesgo R, Savino W. The Impact of Neuroimmune Alterations in Autism Spectrum Disorder. Front Psychiatry. 2015 Sep 9;6:121. doi: 10.3389/ fpsyt.2015.00121.

Perets N, Hertz S, London M, Offen D. Intranasal administration of exosomes derived from mesenchymal stem cells ameliorates autistic-like behaviors of BTBR mice. Mol Autism. 2018 Nov 21;9:57. doi: 10.1186/s13229-018-0240-6.

Zhang R, Cai Y, Xiao R, Zhong H, Li X, Guo L, Xu H, Fan X. Human amniotic epithelial cell transplantation promotes neurogenesis and ameliorates social deficits in BTBR mice. Stem Cell Res Ther. 2019 May 31;10(1):153. doi: 10.1186/s13287-019-1267-0.

Yin K, Wang S, Zhao RC. Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm. Biomark Res. 2019 Apr 4;7:8. doi: 10.1186/s40364-019-0159-x.

Batrakova EV, Kim MS. Development and regulation of exosome-based therapy produ- cts. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2016 Sep;8(5):744-57. doi: 10.1002/ wnan.1395.

Sivanesan S, Tan A, Jeyaraj R, Lam J, Gole M, Hardan A, Ashkan K, Rajadas J. Pharmaceu- ticals and Stem Cells in Autism Spectrum Disorders: Wishful Thinking? World Neurosurg. 2017 Feb;98:659-672. doi: 10.1016/j.wneu.2016.09.100.

Kou M, Huang L, Yang J, Chiang Z, Chen S, Liu J, Guo L, Zhang X, Zhou X, Xu X, Yan X, Wang Y, Zhang J, Xu A, Tse HF, Lian Q. Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool? Cell Death Dis. 2022 Jul 4;13(7):580. doi: 10.1038/s41419-022-05034-x.

Gotoh S, Kawabori M, Fujimura M. Intranasal administration of stem cell-derived exoso- mes for central nervous system diseases. Neural Regen Res. 2024 Jun 1;19(6):1249-1255. doi: 10.4103/1673-5374.385875.

Simberlund J, Ferretti CJ, Hollander E. Mesenchymal stem cells in autism spectrum and neurodevelopmental disorders: pitfalls and potential promises. World J Biol Psychiatry. 2015 Sep;16(6):368-375. doi: 10.3109/15622975.2015.1067372.

Wikarska A, Roszak K, Roszek K. Mesenchymal Stem Cells and Purinergic Signaling in Au- tism Spectrum Disorder: Bridging the Gap between Cell-Based Strategies and Neuro-Immune Modulation. Biomedicines. 2024 Jun 13;12(6):1310. doi: 10.3390/biomedicines12061310.

Li S, Zhang J, Sun L, Yang Z, Liu X, Liu J, Liu X. Mesenchymal stem cell-derived extracellular vesicles: current advances in preparation and therapeutic applications for neurological disor- ders. Front Cell Dev Biol. 2025 Aug 18;13:1626996. doi: 10.3389/fcell.2025.1626996.

Moore D, Meays BM, Madduri LSV, Shahjin F, Chand S, Niu M, Albahrani A, Guda C, Pend- yala G, Fox HS, Yelamanchili SV. Downregulation of an Evolutionary Young miR-1290 in an iPSC-Derived Neural Stem Cell Model of Autism Spectrum Disorder. Stem Cells Int. 2019 May 2;2019:8710180. doi: 10.1155/2019/8710180.

Fakouri A, Razavi ZS, Mohammed AT, Hussein AHA, Afkhami H, Hooshiar MH. Applicati- ons of mesenchymal stem cell-exosome components in wound infection healing: new insigh- ts. Burns Trauma. 2024 Aug 13;12:tkae021. doi: 10.1093/burnst/tkae021.

Ghasemi M, Alizadeh E, Saei Arezoumand K, Fallahi Motlagh B, Zarghami N. Ciliary neurot- rophic factor (CNTF) delivery to retina: an overview of current research advancements. Artif Cells Nanomed Biotechnol. 2018 Dec;46(8):1694-1707. doi: 10.1080/21691401.2017.1391820.

Ma ZJ, Yang JJ, Lu YB, Liu ZY, Wang XX. Mesenchymal stem cell-derived exosomes: Toward cell-free therapeutic strategies in regenerative medicine. World J Stem Cells. 2020 Aug 26;12(8):814-840. doi: 10.4252/wjsc.v12.i8.814.

Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020 Feb 7;367(6478):eaau6977. doi: 10.1126/science.aau6977.

Yayınlanan

15 Temmuz 2026

Lisans

Lisans