Cell transplantation as a novel therapeutic strategy for autism spectrum disorders: a clinical study.
Autologous
PET CT scan
autism spectrum disorders
bone marrow mononuclear cells
cell transplantation
Journal
American journal of stem cells
ISSN: 2160-4150
Titre abrégé: Am J Stem Cells
Pays: United States
ID NLM: 101578936
Informations de publication
Date de publication:
2020
2020
Historique:
received:
07
10
2019
accepted:
25
11
2019
entrez:
25
1
2021
pubmed:
26
1
2021
medline:
26
1
2021
Statut:
epublish
Résumé
Autism spectrum disorders [ASD] is a lifelong disability mainly affecting the development, communication, social interaction and behavior of an individual. Cell transplantation is emerging as a potential therapeutic strategy for ASD. Our previously published proof of concept study showed beneficial effects of cell transplantation in ASD. This study shows effect of cell transplantation in a larger sample size of ASD patients. 254 patients diagnosed with ASD on DSM V criteria were enrolled in this open label non-randomized study. The intervention included intrathecal transplantation of autologous bone marrow mononuclear cells and neurorehabilitation. On mean follow up of 7.50 months, percentage analysis was performed on all symptomatic changes. Changes in outcome measures, Indian Scale for Assessment of Autism [ISAA] and Childhood Autism Rating Scale [CARS], were analyzed statistically using Wilcoxon Signed-Rank Test. Comparative analysis of Positron Emission Tomography [PET CT] scan brain, performed before and 6 months after intervention, was done in 86 patients to monitor the outcome at cellular level. Change in the standardized uptake values was statistically evaluated using T-Test [P≤0.05]. Improvements were observed in eye contact, attention and concentration, hyperactivity, sitting tolerance, social interaction, stereotypical behavior, aggressiveness, communication, speech, command following and self-stimulatory behavior. Statistically significant improvement was observed in scores of ISAA and CARS after intervention. A significantly better outcome of the intervention was found in patients at younger age and with shorter duration of disease [<5 years from time of diagnosis]. 86 patients who underwent a repeat PET CT scan showed improved brain metabolism after intervention in areas which correlated to the symptomatic changes. No major procedure related adverse events were recorded. However, 5 patients, with history of seizure and abnormal EEG, had an episode of seizure which was managed using medications. Outcome of intervention in these patients was not affected by seizures as improvements were observed in them. The results of this study indicate that autologous bone marrow mononuclear cells in combination with neurorehabilitation are a safe and effective treatment modality for ASD. It improves the quality of life of patients and helps them to integrate in mainstream lifestyle.
Sections du résumé
BACKGROUND
BACKGROUND
Autism spectrum disorders [ASD] is a lifelong disability mainly affecting the development, communication, social interaction and behavior of an individual. Cell transplantation is emerging as a potential therapeutic strategy for ASD. Our previously published proof of concept study showed beneficial effects of cell transplantation in ASD. This study shows effect of cell transplantation in a larger sample size of ASD patients.
METHODS
METHODS
254 patients diagnosed with ASD on DSM V criteria were enrolled in this open label non-randomized study. The intervention included intrathecal transplantation of autologous bone marrow mononuclear cells and neurorehabilitation. On mean follow up of 7.50 months, percentage analysis was performed on all symptomatic changes. Changes in outcome measures, Indian Scale for Assessment of Autism [ISAA] and Childhood Autism Rating Scale [CARS], were analyzed statistically using Wilcoxon Signed-Rank Test. Comparative analysis of Positron Emission Tomography [PET CT] scan brain, performed before and 6 months after intervention, was done in 86 patients to monitor the outcome at cellular level. Change in the standardized uptake values was statistically evaluated using T-Test [P≤0.05].
RESULTS
RESULTS
Improvements were observed in eye contact, attention and concentration, hyperactivity, sitting tolerance, social interaction, stereotypical behavior, aggressiveness, communication, speech, command following and self-stimulatory behavior. Statistically significant improvement was observed in scores of ISAA and CARS after intervention. A significantly better outcome of the intervention was found in patients at younger age and with shorter duration of disease [<5 years from time of diagnosis]. 86 patients who underwent a repeat PET CT scan showed improved brain metabolism after intervention in areas which correlated to the symptomatic changes. No major procedure related adverse events were recorded. However, 5 patients, with history of seizure and abnormal EEG, had an episode of seizure which was managed using medications. Outcome of intervention in these patients was not affected by seizures as improvements were observed in them.
CONCLUSION
CONCLUSIONS
The results of this study indicate that autologous bone marrow mononuclear cells in combination with neurorehabilitation are a safe and effective treatment modality for ASD. It improves the quality of life of patients and helps them to integrate in mainstream lifestyle.
Types de publication
Journal Article
Langues
eng
Pagination
89-100Informations de copyright
AJSC Copyright © 2020.
Déclaration de conflit d'intérêts
None.
Références
Free Radic Biol Med. 2014 May;70:141-54
pubmed: 24525001
J Commun Disord. 2011 Sep-Oct;44(5):521-8
pubmed: 21600589
Stem Cells Transl Med. 2017 May;6(5):1332-1339
pubmed: 28378499
Stem Cells Int. 2013;2013:623875
pubmed: 24062774
Cell Transplant. 2012;21 Suppl 1:S79-90
pubmed: 22507683
World J Pediatr. 2010 May;6(2):141-7
pubmed: 20490769
JAMA. 2013 Nov 27;310(20):2191-4
pubmed: 24141714
Stem Cells Int. 2013;2013:262438
pubmed: 24222772
Neuromolecular Med. 2015 Dec;17(4):404-22
pubmed: 26374113
Biol Psychiatry. 2004 Feb 15;55(4):434-7
pubmed: 14960298
Brain. 2000 Sep;123 ( Pt 9):1838-44
pubmed: 10960047
Autism Res. 2016 Jan;9(1):17-32
pubmed: 26257137
Stroke Res Treat. 2014;2014:234095
pubmed: 25126443
J Neurosci. 2009 Nov 25;29(47):14932-41
pubmed: 19940189
Indian J Psychol Med. 2015 Apr-Jun;37(2):169-74
pubmed: 25969602
Phys Med Rehabil Clin N Am. 2003 Feb;14(1 Suppl):S135-42
pubmed: 12625643
Cereb Cortex. 2007 Apr;17(4):951-61
pubmed: 16772313
Indian J Nucl Med. 2016 Apr-Jun;31(2):138-40
pubmed: 27095864
J Neuroinflammation. 2011 Nov 30;8:168
pubmed: 22129087
Cell Tissue Res. 2014 Aug;357(2):493-503
pubmed: 24652503
Curr Top Behav Neurosci. 2013;15:357-98
pubmed: 22907556
Stem Cells Int. 2015;2015:905874
pubmed: 25788947
BMJ. 2011 Oct 21;343:d6238
pubmed: 22021467
World J Stem Cells. 2014 Nov 26;6(5):552-70
pubmed: 25426252
Trends Mol Med. 2012 Aug;18(8):463-71
pubmed: 22771169
PLoS One. 2012;7(12):e50293
pubmed: 23236366
J Transl Med. 2007 Jun 27;5:30
pubmed: 17597540
PLoS One. 2013 Dec 31;8(12):e84116
pubmed: 24391898
Ann Neurol. 2005 Jan;57(1):67-81
pubmed: 15546155
J Transl Med. 2013 Aug 27;11:196
pubmed: 23978163
Cell Transplant. 2014;23 Suppl 1:S105-12
pubmed: 25302490
Neurotox Res. 2013 May;23(4):393-400
pubmed: 23065398
Exp Neurol. 2012 Jan;233(1):312-22
pubmed: 22079829
J Immunol. 2011 Apr 15;186(8):4973-83
pubmed: 21402900
Cell. 2011 Jul 8;146(1):18-36
pubmed: 21729779
Neurotoxicol Teratol. 2013 Mar-Apr;36:67-81
pubmed: 22918031
Toxics. 2015 Mar 23;3(1):89-129
pubmed: 29056653
Stem Cells Cloning. 2018 Oct 23;11:55-67
pubmed: 30425534
Front Neurol. 2015 Apr 08;6:81
pubmed: 25904895
Clin Med Pathol. 2008;1:99-103
pubmed: 21876658
Iran Biomed J. 2013;17(1):8-14
pubmed: 23279829
Stem Cells Transl Med. 2018 Apr;7(4):333-341
pubmed: 29405603
Front Hum Neurosci. 2013 Sep 27;7:609
pubmed: 24098278
Stem Cells Int. 2013;2013:130763
pubmed: 24194766
Free Radic Biol Med. 2012 May 15;52(10):2128-41
pubmed: 22542447
Front Psychiatry. 2015 Sep 09;6:121
pubmed: 26441683
J Neurosurg. 2015 Apr;122(4):856-67
pubmed: 25594326
Stem Cell Res. 2009 Jul;3(1):63-70
pubmed: 19411199
Stem Cells Dev. 2007 Oct;16(5):747-56
pubmed: 17999596
Stem Cells Dev. 2009 Jun;18(5):683-92
pubmed: 19099374