Shravanthi Chidambaram, PhD
Association for Science in Autism Treatment

Scott M. Myers, MD
Geisinger Autism & Developmental Medicine Institute

Stem cell therapy has successfully treated a number of diseases like leukemia (Aversa et al., 2001), lymphoma (Zahid et al., 2017), aplastic anemia (Georges & Storb, 2002), and others, generating enormous curiosity in its potential and application in medicine. Understanding the vast archive of information that is available on stem cell therapy can be quite an arduous task. As consumers of any new technology or treatment, it is vital to fully understand stem cell therapy before making an informed decision, to see whether it is a viable and safe option. This becomes even more important when you consider a population as vulnerable as children with autism. Let us start by discussing a few basic concepts about stem cells.

What are stem cells?

It is common knowledge that the body is made up of functional units called cells, which collectively make up the tissue and organs in our bodies. During normal cell division, a cell divides into two. Both cells formed are the same (i.e., the same cell type). Stem cells are special in that they have the ability to develop into different cell types, while also making one of itself during division, in a process known as self-renewal. Broadly there are two types of stem cells:

  1. Embryonic stem cells (ESCs): These are stem cells obtained from early-stage embryos, which have the potential to divide into any cell type in the body. The embryos used for research are left over from those made in the lab during in vitro fertilization (IVF) treatments, where several are created at one time during this process. There is ethical debate as to its use in research and therapy (King & Perrin, 2014; Volarevic et al., 2018).
  2. Adult stem cells (ASC): These are stem cells that are found in adult tissue/organs in small numbers. Although the name might be misleading, these also include stem cells found in infants and children (any stem cell of non-embryonic origin). These cells are more limited in the types of cells they can produce. For example, Hematopoietic Stem Cells (HSC) or blood stem cells can only give rise to the different cell types present in blood but cannot give rise to brain or liver cells. These cells periodically divide to produce and replace cells within a tissue or organ (Snippert & Clevers, 2011; Young & Black Jr., 2004).

The journey to discovering the causes of autism

Like other neurodevelopmental disorders such as intellectual disability, autism spectrum disorder (ASD) has many different causes, including variants in more than 100 genes (Satterstrom et al., 2020). Using genetic testing, about 25% of gene variants can be associated with individuals with ASD (Savatt & Myers, 2021; Srivastava et al., 2019), although a unifying underlying cause is yet to be identified (Chen et al., 2015; de la Torre-Ubieta et al., 2016). There is also evidence suggesting that infections and autoimmune disorders in the mother during pregnancy may contribute to the pathology of ASD by creating an inflammatory environment in the fetal brain (Grabrucker, 2013; Hughes et al., 2018; Meltzer & Van de Water, 2017; Patterson, 2011). Multiple lines of evidence implicate dysfunction of synapses, which are sites of communication between neurons, in the biology of ASD (Carroll et al., 2021; Guang et al., 2018). Yet, other studies show that hormonal imbalance (Kosidou et al., 2016; Yau et al., 2015), exposure to toxins (Kinney et al., 2010), and other environmental factors (Grabrucker, 2013) may contribute to ASD. This body of evidence leaves us with more questions than answers. So, treating a condition where the cause is still such a mixed picture should be done with great caution and transparency.

How might stem cell therapy fit in with ASD?

The basis for almost all ASD studies involving stem cells largely comes from harnessing their inherent properties (Caplan & Dennis, 2006). Stem cells naturally secrete small proteins called cytokines and growth factors, which could suppress the inflammatory environment in the brain of children with ASD. These immunomodulatory properties (something that can control the immune system) make them extremely attractive. However, the evidence for inflammation in the prenatal brain is not adequate enough to pursue stem cell therapy just yet. Other evidence suggests (Liu et al., 2019; Siniscalco et al., 2013) synaptic dysregulation (upsetting connections between the neurons) to be a crucial source for the behavioral symptoms seen in ASD patients (Sacai et al., 2020), and using stem cells that secrete specific factors was able to restore this synaptic function in mouse models of ASD (Perets et al., 2018; Segal-Gavish et al., 2016). Perhaps the most remarkable application for stem cells does not involve administering them to patients but using them as a model to study the disease in the lab (Ardhanareeswaran et al., 2015). Scientists collect skin cells (a less invasive procedure than collecting stem cells from the bone marrow) from patients, and then genetically manipulate them in the lab into the cell type they wish to study. They then screen drug compounds or other treatments on the cells generated, making the therapy more targeted (Trujillo et al., 2021). This research opens up safer possibilities to study effective therapies for ASD without having to directly try them on patients.

How successful has stem cell therapy been in ASD so far?

As of December 2019, there were 13 trials looking at stem cell therapies in ASD reported on Of these, two were “withdrawn,” and two were “unknown status.” Seven were completed and four were active. Of the completed, only one well-designed controlled clinical trial had been published or reported its data to, and it showed no benefit of stem cell therapy; there was no significant change in any tests over pre-treatment assessments. This article (Price, 2020) describes the trials well. Trials performed so far leave us with modest evidence of safety, but very little evidence of stem cell therapy’s actual effectiveness for treating ASD. Experts in the field still question the veracity of these trials concerning their hypotheses, trial design, methods of measuring the results, and their interpretation. The variability in the studies makes comparisons harder, subsequently making it harder to arrive at robust conclusions.

What to look out for when considering stem cell therapies?

As more research is published in this area, there will be several things to consider when you are contemplating stem cells therapies. This ‘closer look at stem cells’ source provides a brief review of the important things to consider. Broadly, when considering these therapies, you need to learn about the type of stem cell used in the therapy. Secondly, request evidence for the science behind why that cell type is being used, what it is meant to do, and what measurable results you can expect to see. Make sure these results are not subjective, which can usually be explained away. For example, if the therapy is meant to reduce inflammatory cytokines, look for actual values of these proteins in the serum of the blood. Thirdly, learn about the mode of administration. This is critical, as some studies do not report adverse effects caused by the route of administration. Further, learn about the dosage that will be administered. Also stem cell therapy should only be considered when it is a part of a well-designed and evidence-based clinical trial. Brenden Borrell (2019), wrote an article for Spectrum asking parents and caregivers to beware of clinics providing stem cell therapies as part of clinical care, outside of supervised clinical trials. Most of all, make sure any decisions you make regarding therapy for you or your children are always evidence-based.

Bottom line

Stem cell research has come a long way since its advent about 50 years ago, and doctors now routinely use approved bone marrow stem cell transplantation to treat cancer (Aversa et al., 2001; Zahid et al., 2017) and disorders of the blood and immune system (Georges & Storb, 2002; Traynor et al., 2000). Stem cell therapy may have potential for application in ASD, but the research is still in its infancy. While there is so much yet to learn about ASD and its causes, it is premature to start treating patients without thoroughly assessing the risks that these treatments might pose, especially since there are low risk, evidence-based treatment options currently available that have well-documented results. For now, we should rely on those proven methods of treatment, such as applied behavior analysis (ABA, (Roane et al., 2016)).

Citation for this article:

Chidambaram S., & Myers, S. (2021). Stem cell therapy: Is there science behind that? Science in Autism Treatment, 18(3).

Other Related “Is There Science Behind That?” Articles:

Other ASAT Related Articles:

Related Media Watch Letters:


Ardhanareeswaran, K., Coppola, G., & Vaccarino, F. (2015). The use of stem cells to study autism spectrum disorder. The Yale Journal of Biology and Medicine88(1), 5.

Aversa, F., Velardi, A., Tabilio, A., Reisner, Y., & Martelli, M. F. (2001). Haploidentical stem cell transplantation in leukemia. Blood Reviews15(3), 111-119.

Borrell, B. (2019, March 27). False hope for autism in the stem-cell underground.

Caplan, A. I., & Dennis, J. E. (2006). Mesenchymal stem cells as trophic mediators. Journal of Cellular Biochemistry98(5), 1076-1084.

Carroll, L., Braeutigam, S., Dawes, J. M., Krsnik, Z., Kostovic, I., Coutinho, E., Dewing, J.M., Horton, C. A., Gomez-Nicola, D., & Menassa, D.A. (2020). Autism spectrum disorders: Multiple routes to, and multiple consequences of, abnormal synaptic function and connectivity. The Neuroscientist,

Chen, J. A., Peñagarikano, O., Belgard, T. G., Swarup, V., & Geschwind, D. H. (2015). The emerging picture of autism spectrum disorder: Genetics and pathology. Annual Review of Pathology: Mechanisms of Disease10, 111-144.

De la Torre-Ubieta, L., Won, H., Stein, J. L., & Geschwind, D. H. (2016). Advancing the understanding of autism disease mechanisms through genetics. Nature Medicine, 22(4), 345–361.

Georges, G. E., & Storb, R. (2002). Stem cell transplantation for aplastic anemia. International Journal of Hematology75(2), 141-146.

Grabrucker, A. M. (2013). Environmental factors in autism. Frontiers in Psychiatry3, 118.

Guang, S., Pang, N., Deng, X., Yang, L., He, F., Wu, L., Chen, C., Yin, F., & Peng, J. (2018). Synaptopathology involved in autism spectrum disorder. Frontiers in Cellular Neuroscience12, 470.

Hughes, H. K., Ko, E. M., Rose, D., & Ashwood, P. (2018). Immune dysfunction and autoimmunity as pathological mechanisms in autism spectrum disorders. Frontiers in Cellular Neuroscience12, 405.

King, N. M. P., & Perrin, J. (2014). Ethical issues in stem cell research and therapy. Stem Cell Research & Therapy5(4), 1-6.

Kinney, D. K., Barch, D. H., Chayka, B., Napoleon, S., & Munir, K. M. (2010). Environmental risk factors for autism: Do they help cause de novo genetic mutations that contribute to the disorder? Medical Hypotheses74(1), 102-106.

Kosidou, K., Dalman, C., Widman, L., Arver, S., Lee, B. K., Magnusson, C., & Gardner, R. M. (2016). Maternal polycystic ovary syndrome and the risk of autism spectrum disorders in the offspring: a population-based nationwide study in Sweden. Molecular Psychiatry21(10), 1441-1448.

Liu, Q., Chen, M. X., Sun, L., Wallis, C. U., Zhou, J. S., Ao, L. J., Li, Q., & Sham, P. C. (2019). Rational use of mesenchymal stem cells in the treatment of autism spectrum disorders. World Journal of Stem Cells11(2), 55.

Meltzer, A., & Van de Water, J. (2017). The role of the immune system in autism spectrum disorder. Neuropsychopharmacology42(1), 284-298.

Patterson, P. H. (2011). Maternal infection and immune involvement in autism. Trends in Molecular Medicine17(7), 389-394.

Perets, N., Hertz, S., London, M., & Offen, D. (2018). Intranasal administration of exosomes derived from mesenchymal stem cells ameliorates autistic-like behaviors of BTBR mice. Molecular Autism9(1), 1-12.

Price, J. (2020). Cell therapy approaches to autism: A review of clinical trial data. Molecular Autism11, 1-9.

Roane, H. S., Fisher, W. W., & Carr, J. E. (2016). Applied behavior analysis as treatment for autism spectrum disorder. The Journal of Pediatrics175, 27-32.

Sacai, H., Sakoori, K., Konno, K., Nagahama, K., Suzuki, H., Watanabe, T., Watanabe, M., Uesaka, N., & Kano, M. (2020). Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex. Nature Communications11(1), 1-15.

Satterstrom, F. K., Kosmicki, J. A., Wang, J., Breen, M. S., De Rubeis, S., An, J. Y., Peng, M., Collins, R., Grove, J., Klei, L., Stevens, C., Reichert, J., Mulhern, M.S., Artomov, M., Gerges, S., Shepperd, B., Xu, X., Bhaduri, A., & Demontis, J. D. (2020). Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Cell180(3), 568-584.

Savatt, J. M., & Myers, S. M. (2021). Genetic testing in neurodevelopmental disorders. Frontiers in Pediatrics, 9, 52.

Segal‐Gavish, H., Karvat, G., Barak, N., Barzilay, R., Ganz, J., Edry, L., Aharony, I., Offen, D., & Kimchi, T. (2016). Mesenchymal stem cell transplantation promotes neurogenesis and ameliorates autism related behaviors in BTBR mice. Autism Research9(1), 17-32.

Siniscalco, D., Bradstreet, J. J., Sych, N., & Antonucci, N. (2013). Perspectives on the use of stem cells for autism treatment. Stem Cells International2013.

Snippert, H. J., & Clevers, H. (2011). Tracking adult stem cells. EMBO Reports12(2), 113-122.

Srivastava, S., Love-Nichols, J. A., Dies, K. A., Ledbetter, D. H., Martin, C. L., Chung, W. K., Firth, H. V., Frazier, T., Hansen, R. L., Prock, L., Brunner, H., Hoang, N., Scherer, S. W., Sahin, M., & Miller, D. T. (2019). Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genetics in Medicine21(11), 2413-2421.

Traynor, A. E., Schroeder, J., Rosa, R. M., Cheng, D., Stefka, J., Mujais, S., Baker, S., & Burt, R. K. (2000). Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study. The Lancet356(9231), 701-707.

Trujillo, C. A., Adams, J. W., Negraes, P. D., Carromeu, C., Tejwani, L., Acab, A., Tsuda, B., Thomas, C. A., Sodhi, N., Fichter, K. M., Romero, S., Zanella, F., Sejnowski, T. J., Ulrich, H., & Muotri, A. R. (2021). Pharmacological reversal of synaptic and network pathology in human MECP2‐KO neurons and cortical organoids. EMBO Molecular Medicine.

Volarevic, V., Markovic, B. S., Gazdic, M., Volarevic, A., Jovicic, N., Arsenijevic, N., Armstrong, L., Djonov, V., Lako, M., & Stojkovic, M. (2018). Ethical and safety issues of stem cell-based therapy. International Journal of Medical Sciences15(1), 36.

Yau, V. M., Lutsky, M., Yoshida, C. K., Lasley, B., Kharrazi, M., Windham, G., Gee, N., & Croen, L. A. (2015). Prenatal and neonatal thyroid stimulating hormone levels and autism spectrum disorders. Journal of Autism and Developmental Disorders45(3), 719-730.

Young, H. E., & Black Jr, A. C. (2004). Adult stem cells. The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology: An Official Publication of the American Association of Anatomists276(1), 75-102.

Zahid, U., Akbar, F., Amaraneni, A., Husnain, M., Chan, O., Riaz, I. B., McBride, A., Iftikhar, A., & Anwer, F. (2017). A review of autologous stem cell transplantation in lymphoma. Current Hematologic Malignancy Reports12(3), 217-226.

Print Friendly, PDF & Email