Do I need to take my child out of the country?
The choice is ultimately yours, but let me help a bit with the information. The global stem cell market is projected to reach 32 Billion by 2030 and the potential uses for stem cells have risen exponentially in recent years, as stem cells have the ability to self-renew and differentiate, meaning that can potentially be used for different purposes or places within the body. Stem cells may also be beneficial because of their paracrine function (chemical signals that communicate with nearby cells). Stem cells are intended to integrate into the site of the damaged cells and replace the injured tissue improving the function of the tissue. So why do scientists feel stem cells may be beneficial from autism specifically? Well, we know that several research studies have identified pro-inflammatory state and immune dysregulation have been associated with ASD. More specifically, pro-inflammatory cytokine levels and elevated microglia/astrocytes (immune cells in the brain) leading to aberrant neurodevelopment. Those with ASD has differing levels of expression for neuron-related RNAs. These RNA alterations consistently point to dysregulated networks involved in synaptic transmission, neuronal differentiation and apoptosis (cell death), reflecting impaired gene expression regulation during neurodevelopment. There has also been evidence of increased mitochondrial DNA in ASD patients because mitochondrial DNA is a trigger of microglial inflammation process.
Most stem cells are donated from bone marrow, adipose tissue (fat), umbilical cord, placenta, embryos and dental pulp. Across the different types of stem cells, they fall into two categories depending on where they originated from. Autologous cells (often iPS, adipose, umbilical) come from the person’s own body and are more favorable because they generally avoid immune rejection or use of immunosuppressants, ethical issues, and the need for donors. In fact, you can use autologous stem cells even if they are from the person with ASD and/or genetic disorder. Allogenic transplants are donated, but may be required for cells that are therapeutic (often fetal, embryonic, NSPCs, dental pulp, and hematopoietic). So let’s discuss the different sources of stem cells and what their potential uses are. Induced pluripotent stem (iPS) cells (autologous, from own body), embryonic (derived from surplus blastocysts), umbilical (from donated umbilical cord blood or tissue/whartons jelly), donated adult stem cells (allogenic). Within these types of stem cells, some are mesenchymal stem cells, which are often preferred. For example, umbilical cord blood and adipose-derived mesenchymal stem cells are easy to isolate and purify and secrete immune blocking factors and as such are less likely to cause immune rejection. MSCs are multipotent (specialized) cells that can differentiate into various cell types, can be transdifferentiated into neural cells, easily obtained from many sources, can self-renew, low tumor and immune rejection risk, appear to be effective for neurological conditions, for neurogenesis, anti-apoptosis (cell death), and anti-inflammation, can cross the BBB via IV, sometimes co-transplantation with neural stem cells may improve efficacy, the younger age and source matter as well, MSCs have low immunogenicity aids in long-term survival, also secrete BDNF (brain-derived neurotropic factor) and NT-3 (neurotropin growth factor), proteins that enhance neuronal survival, regeneration, and efficiency. A newer type of stem cell that has also been receiving attention are MUSE cells, which stands for multilineage-differentiating stress enduring cells) are noncancerous pluripotent stem cells present in many cells in the body including MSCs, present in cultured MSCs, may be more therapeutic for tissue regeneration, unlikely to cause tumors or immune rejection, can integrate into damaged regions and differentiate via IV injection but not as studied as some other cells, more newly discovered. Neural stem/progenitor cells are multipotent cells (can divide and turn into specialized cells or tissues) that can self-renew and generate the main types of cells in the CNS including neurons and other brain cells, lower tumor risk, more specialized, typically donated from fetuses or other stem cells, can cause immune rejection, MSC-dervied neural stems cells are preferred in clinical studies (phase 1/2), safe but clinical effectiveness not yet established.
Now, aside from straight-up stem cell therapy, newer therapies have involved smaller parts of the cells, called exosomes, a type of extracellular vesicle. Mesenchymal stem cell therapy and stem-cell derived exosome therapy are two different kinds of interventions. Exosomes can be found in amniotic fluid, blood, CSF, breast milk etc. EVs are secreted from many cells in the blood and other biological fluids and carry molecules that could influence the function of target cells. Exosomes regulate several key cellular functions and can alter the activity of target cells by transferring DNA, RNA and proteins (cargo). exosomes originate from mesenchymal stromal cells as well as other types of cells, they are able to merge and secrete they contents into recipient cells and control biochemical pathways in the target cells. Exosomes are stable and interact with RNA/DNA in the recipient cells. Exosomes act as shuttles to send nucleic acids and proteins to other cells to allow cell to cell communication and transport of molecules among close and distant cells. Through RNA, stem cells are able to transfer bioactive factors to other cells, affecting their function, can repair damaged molecular pathways within an ASD brain. Exosomes regulate intercellular communication and the extracellular matrix and influence proliferation and differentiation. Stem cells release exosomes to communicate with other cells, exosomes are made up of nucleic acids, proteins, lipids, and metabolites, assumed to have therapeutic function. Exosomes can signal over short range within brain tissue and through CSF. Exosomes are able to cross the blood-brain barrier and stimulate neuronal differentiation and growth and suppress inflammatory process within the brain tissue. In fact, Exosomes can potentially serve as a biomarkers for ASD. Children with ASD show altered integrity of the BBB so certain cells and proteins may not be able to cross, but it appears exosomes can. A panel of EV proteins may serve as non-invasive biomarkers for ASD, which may inform potential therapeutic strategies These exosomal biomarker studies are vital in ASD research as they provide valuable insights into the underlying mechanisms of the disorder, aid in early detection, and offer potential targets for therapeutic interventions. Moreover, exosomes may be safer than stem cells because they cannot self-replicate, so risk of tumors is eliminated, they are also stable enough to be frozen long-term or freeze dried and stored at room temperature, can be sterilized more easily because of their small size, even inhaled via a nebulizer instead of more intrusive administration. The thought is that exosomes may serve as mediators of many of the stem-cell associated therapeutic activity and exert anti-inflammatory activities (stimulation of anti-inflammatory cytokine production) and also improve GI function via the brain-gut connection. Exosomes have been suspected to play a protective role by dumping pathological molecules out of cells and promote healthy neural development. Exosome membrane lipids can enhance synapse formation and stability, thereby influencing the functional properties of recipient cells which improve cognition and behavior. Compared with direct stem cell transplant, exosomes provide greater safety, controllability, and ease of storage and are “cell-free therapy.”
The research has been promising overall; however, insufficient research has been completed to date to make any definitive conclusions regarding ASD specifically as of now. Here is what we do know. Transplantation of adipose-derived MSCs into the brain of newborn mice reduced repetitive and anxious behaviors and increased social behaviors in mice exposed to VPA and can restore hippocampal neuronal development. Human Stem cell therapy clinical trials for ASD have been completed in at least 7 countries, typically phase 1/2 open-label with umbilical or bone marrow. In 2013, cord blood with umbilical cord derived MSCs was transplanted in children to be safe and well-tolerated with some improvements in language and behavior.
Clinical trial from 2019 showed improvement in ASD symptoms after IV injection of MSCs but only in 8 children with no major side effects, Repeated (12 weeks) infusions with umbilical cord MSCs result in only mild to moderate short-lived effects (headaches, fever fatigue), improvement in symptoms and reduced inflammatory cytokine levels, single arm, phase 1/2 clinical trial, followed of 1 year, therapeutic effects often declines after 3-6 months likely due to the immune-evasive properties of MSCc which are ultimately eliminated, lack of placebo group. Another Clinical trial in 2021phase 1 open-label of single IV injection of autologous steel cells young children most behaviors improved within 6 months, autologous umbilical cord blood infusions, safe, well-tolerated (agitation, skin changes), and effective (adaptive, language, nonverbal iq, and behavior), no control group and improvements could be due to other reasons. Two recent clinical trial completed in 2025 and 2026 was a phase 1 open-label Mesenchymal stromal cell therapy in toddlers (1-3) with autism and a phase 2 study Mesenchymal stromal cell therapy in children (4-11) via Duke University Center for Autism and Brain Development, the children received on IV infusion human umbilical cord tissue-derived MSCs with assessment at 6 and 12 months assessing social communication, adaptive behavior, inattention, eye tracking, and brain activity, no findings have been reported yet. Presently, research on use of stem cells for ASD is in the clinical trial stage (open-label phase 1/2), still need to demonstrate clinical efficacy, though safety appears to have been established. An open-label clinical trial in Vietnam with young children using autologous bone marrow with behavioral intervention and saw an improvement in symptoms. In children with ASD, stem cell treatment has been shown to regulate the glucose metabolism resulting in improved cognitive and behavioral symptoms as well as motor functioning. Human embryonic stem cells resulted in improvements in motor skills, cognition, and social interaction with reduced sensory sensitivities , White matter increases in the social communication regions. Stem cell therapy has been shown to increase white matter connectivity in the brain both in cortex and subcortical structures. Some studies suggest intrathecal injection (into CSF) of stem cells may be more effective if IV injection is blocked by BBB. It is hard to say whether improvements are the results of natural course of disorder and/or other interventions. Overall, some studies have shown significant improvement in social communication, adaptive functioning, eye contact, and restricted/repetitive behaviors, more evidence in an open-label (aware of what treatment is being given) vs. placebo design, 2 RCTs revealed behavioral symptoms of ASD in response to stem cell therapy, but there were difficulties assessing valid cognitive function in the young children.
Similar to traditional stem cell therapy, the research on stem-cell derived exosome therapy has also been promising based upon animal and human studies. Extracellular vesicles (EVs) released from neural stem cells in different regions of the nervous system were involved in several aspects of brain function an can improve function in damaged tissue. Exosome treatment was able to activate pro-survival pathways by increasing the concentrations of ATP and reducing oxidative stress. Bone marrow-extracted MSC-derived exosomes showed a capacity to block the release of pro-inflammatory molecules. High turnover rates of microglia in some pathological neurological conditions, can be regulated by MSC-exosomes In fact, exosomes have been shown to reduce amyloid plaques in mouse models. EVs isolated from the serum of patients with ASD stimulated with cultured human microglia (stem-cell derived human brain immune cells) secreted significantly more of the pro-inflammatory cytokine as compared to controls. Injection of neural stem cell derived exosomes into the lateral ventricle can increase the proliferation of hippocampal neurons and stimulate synaptic growth and neural circuit developmental in rat brains. For autism spectrum symptomatology and associated genetic disorders (retts, phelan-mcdermid) animal studies were generally consistent and positive. This is consistent with what would be expected given that increased extracellular vesicle-associated protein was shown in the ASD group compared to controls and contained more mitochondrial DNA which may be a trigger for microglia resulting in inflammation. Using MSC derived exosomes for treatment in ASD models as stem cell treatments in mice showed improvements in symptoms. Exosomes derived from MSCs (intranasal) had a direct beneficial effect on autistic behaviors in genetically modified SHANK3B knock-out mice. Exosomes were able to rescue the decrease in neuronal growth and differentiation as well as synaptogenesis in those with MECP2 mutation (retts). Exosomes have been shown to reverse the developmental deficits caused by the genetic mutation in retts. Increase of GABA (a neurotransmitter that is often low in those with ASD) in the prefrontal cortex after treatment with MSC-exosomes. Exosomes extracted from human umbilical cord MSCs were able to alleviate brain neuroinflammation by regulating microglia in mice when administered intranasally. Intranasal delivery of exosomes from human umbilical cord MSCs decreased social deficits repetitive behaviors and regulated neuroinflammation in VPA mice. Intranasal administration has been shown to be an effective and noninvasive route to deliver exosomes to the brain for other neurologically based disorders and also allows for small molecule drugs to be encapsulated within exosomes and delivered to the brain to treat inflammation. Finally, Brain-specific delivery of human umbilical cord MSC exosomes has shown potential in alleviating ASD phenotypes in rats.
Despite this seemingly encouraging research across species, stem cell sources, and approaches, there still remain some significant barriers to availability and acceptance of stem cell therapy. There is still no standardized protocol of treatment, most studies have small sample sizes. We are still understanding the precise mechanisms of action within stem cell therapy. Concerns of MSCc are immunorejection, difficulty with proliferation, and transplantation safety. Donor stem cells carry antigens (anything that alerts an immune response in the body) that may elicit an immune response. Doses of cell injections were widely varied across studies. Only a small amount of the MSCc will end up proliferating (growth/multiplication) and differentiating into the desired site. The ability of cord blood cells to form the missing or damaged neural cells likely relies on method of administration and cellular environments. Because of this, Outcomes influenced by cost, availability, route of administration, cell quantity, IV and intranasal safer but can deal with loss of cells and it is not a case of “the more the better” because can lead to adverse reactions. Variations in MSC culture conditions and tissue sources can produce substantial differences in exosome yield and quality, there are no standard protocols for extracting, purifying, and characterizing exosomes, comprehensive preclinical safety evaluations are necessary to assess long-term risks, ethical and legal considerations can be critical as well. One limitation is the yield of exosome production per cell to establish optimal therapeutic dose, administration route, number of treatments, and individual pharmacokinetics of the person receiving treatment. These therapies would rely upon large-scale manufacturing of stem cells and exosomes in good manufacturing practice (GMP) facilities as well as quality control to minimize the variance between batches of exosomes. One limitation is that there is no single definitive molecule that has been consistently identified as an exosomal biomarker, multiple molecules may need to be considered in order to tailor more personalized treatment approaches. Concerns are that ASD is not a neurodegenerative disorder, significant variation in ASD, critical developmental period of development is unknown (when would be most effective). Interestingly, for clinical studies, genetic conditions (e.g., Rett’s, Phelan-McDermid, Fragile X) were exclusion criteria for eligibility but I wonder if theses are the “types” of autism that would most benefit from stem cell therapy?
And what about the legality of stem cell treatment in different countries? The FDA and Health Canada and the EMA in the EU have approved stem cell therapy for some very specific clinical uses/illnesses (including a few stem cell products derived from mesenchymal stem cells) but not for ASD. The FDA has recently approved some cell-based therapies for specific rare conditions. US FDA has cited inadequate clinical evidence to support access to this treatment outside of clinical trials at this time. The International Society for Stem Cell Research (ISSCR) and the International Society for Extracellular Vesicles have proposed guidelines to address divisive issues in stem cell and exosome research but no current consensus on clinical translation of these approaches. Once a new therapy is tested and shows promise within a laboratory setting, clinical trials can being to be used with human volunteers in an ethical manner, if proven to be effective (more effective than a placebo and/or alternative treatments) and safe, a regulatory body can be authorized and marketed, and then monitored for long-term safety and clinical efficacy via randomized-controlled trials which have been published in peer-reviewed journals prior to be deemed an empirically supported treatment. If the stem cells are considered to be.a biological product or drug (e.g., donor tissue combined with other substances), then they must be regulated by the FDA (regulation 351, requires clinical trial data and formal application). If the cells are minimally processed and taken from the patient’s own body, then does not require FDA approval, if minimally processed and used for their natural function (regulation 361, only needs to be registered and follow basic safety standards). Stem cell clinics in the USA generally have minimal oversight (with a few exceptions), with some promoting misleading or unsupported claims. States can pass their own laws as well, Florida passed a law in 2025 (i.e., SB 1768) allowing licensed physicians more leniency with stem cell therapies that don’t have FDA approval as long as the products come from FDA-registered and accredited facilities, the biologics must come from ethically sourced tissue and not from embryonic or fetal cells, also requires honest advertising and informed consent and regulated by the Florida Department of Health. In 2026 the FDA has sent warning letters to clinics in Florida, California, and Texas who were administered unapproved exosome products. In closing, Be careful if: a clinic claims to treat an unusually wide range of conditions, staff can’t or won’t explain where the cells came from, you are promised a result/cure, there is no FDA registration or accreditation for the stem cell source, need to be honest about risks (e.g., infection). Many institutes are located in countries with less stringent medical standards without significant and formal research trials, as a result It may be unethical and premature to allow this treatment to be marketed to families. If receiving a stem cell treatment for ASD, it is best to temper expectations and not make accept promises of significant improvement based upon lack of evidence and information. And finally, expanding multi center large sample RCTs will be crucial to best understanding the effects of stem cell therapies, with the potential to combine stem cell therapy with gene editing in the future- so stay tuned! And, now I have the pleasure of speaking the to founder of one of these legal and transparent stem cell clinics so we can learn about the beginnings of the availability of stem cell treatment in the US.