Autism is a neurodevelopmental disorder that affects a person’s social communication and interaction and shows repetitive patterns or behavior. Moreover, autism is a subgroup of autism spectrum disorder. Above all, a recent study related to autism reports that globally around 61.8 million people are affected with ASD. Patients with ASD show different symptoms and characteristics.

Stem cell therapy has revolutionized the treatment of Autism Spectrum Disorder in autistic adults. Basically, mesenchymal stem cells from bone marrow, adipose tissue and Umbilical cord tissue are tipped to be the best cells for ASD treatment. People who receive stem cells for autism report social skills, communication, and motor skills improvement.

History of Mesenchymal Stem Cells (MSCs)

In the 1960s, Alexander Friedenstein uncovered that bone marrow is not only a source of hemopoietic stem cells but also contains cells which originate from mesenchyme. So in the year 1991, Kaplan suggested that the cells that originate from mesenchyme region be named as mesenchymal stem cells. Hence, since 1991, the cells from mesenchyme origin are labelled as mesenchymal stem cells.

In 2006, International Society of Cellular Therapy (ISCT) put forward the criteria that MSC should meet to classify as mesenchymal stem cells:

Generally, should be able to differentiate into adipocytes, chondroblasts, and osteoblasts.
Moreover, under in vivo conditions, must be plastic adherent with fibroblast like similarity.
It should express CD105, CD90 and CD73 molecules and should not express CD11b, CD14, CD19, CD34, CD45 surface molecules.

The potential of mesenchymal stem cells (MSCs)

MSC are a group of progenitor cells that have the ability to self-renew and self-regenerate. The MSCs can be obtained from various sources like adipose tissue, bone marrow, umbilical cord blood, umbilical cord Wharton’s jelly, etc. Additionally, the other properties of MSCs are immunomodulation, anti-inflammation, anti-apoptosis and angiogenesis.

Why choose MSC for treating Autism Spectrum Disorder

MSC not only poses a unique property of immunomodulation but also have the ability to self-renew and regenerate.

Generally, MSCs are easy to collect, store and can also be easily transported.
MSCs do not carry the risk of tumorigenesis as seen in embryonic stem cells.
Moreover, MSC has no ethical considerations unlike embryonic stem cells.

MSCs impact on nervous system

The main mechanism of action of MSC in ASD is likely to be neurogenesis, synaptogenesis and neuroprotection.
MSCs secrete growth factors like nerve growth factor and brain-derived neurotrophic factor which play an important role in synaptic transmission.

Impact of MSCs on the immune system

Firstly, MSCs have the ability to restore immune balance by increasing the levels of IL-10 and IL-4 levels and reducing levels of TNF-α, IL-1β and IFN-γ.
The special property of MSC is that it has the ability to cross blood-brain barrier.
MSC promotes maturation of neuronal cells and increases levels of brain-derived neurotrophic factor which restores neurogenesis.
They also reduce repetitive behaviors, and enhance cognitive function.
Similarly, MSC derived exosomes suppress inflammatory immune response, modulates immune system and repairs and restores damaged tissue.
Above all, MSC also improves functions like cognition, language, speech, behavior and communication.

Progress of Autism Spectrum Disorder

According to hypothesis, development of ASD occurs on the following sequence of events.

Certain infections and release of auto-immune antibodies during neuronal development stage.
Leads to immune dysregulation and activation of inflammatory process which in turn alters gut microbiota and blood-brain barrier permeability.
Subsequently alters brain functions.

Immunomodulatory activities of MSCs

The ability of MSC is to exhibit both immunomodulatory and immunosuppressive functions.

MSC and T cell:

When the MSC come in contact with T cells, they reduce activation and proliferation of T cell by increasing Treg cells and expression of IL-10. It also reduces Th1, Th2 and Th17 cells. The mechanism of action stimulates release of cytokines, growth factors and enzymes.

MSC and B cell:

It is known to inhibit B cell proliferation and differentiation by secreting IFN-γ inducible IDO. They also stimulate expansion of B-reg.

On interaction, MSCs inhibit proliferation and activation of NK cells. For suppressing NK cell function, the PGE2 release plays a major role. Thus, the overall effect results in decrease in cytotoxicity due to NK cells.

MSC and myeloid cells:

MSc stops the secretion PGE2 and IL-6 and stops the proliferation of monocytes into dendritic cells. Interaction between MSC and M1 macrophages also increases immunosuppressive function.

S.no	Dysregulation	MSC mechanism
1.	Increase in pro-inflammatory cytokine and decrease in ant-inflammatory cytokines	Increase in synthesis of certain growth factors and anti-inflammatory cytokines.
2.	Alteration in T cell, B cell and NK cell activity	Inhibits proliferation of T cell, B cell and NK cell and regulates immune response.
3.	Increase in astrocyte and microglial cells	Inhibits activation and proliferation and in turn provides neuroprotection.
4.	Neuronal changes and alteration in synapse function	Promotes synaptogenesis and secretes neurotrophic factors that promote survival of neurons.

Mechanisms of MSCs in autism

MSC exert therapeutic effect and reduce dysregulation of immune system by suppressing immune response.
MSC inhibit process of neural cell death, proliferation of astrocyte and microglial cell activation which ultimately leads to neuroprotection.
Additionally, they also secrete neurotrophic factors that promote survival of neuron.
It also reduces the number of microglial cells along with activation.
Above all, they also trigger the action of neural progenitor cells in order to restore and regenerate the neurological pathway.
Furthermore, MSC also play an important role in stimulating synaptic function and formation.

Benefits of MSC in ASD

The MSCs are a potential treatment option in Autism Spectrum Disorder. The multiple benefits of MSC in autism are:

Increase in cognition: MSCs also enhance neurogenesis i.e. it promotes growth of neurons and reduce inflammation. Additionally, improves brain cognitive and learning potential.
Improvement in social skills and communication: MSCs have the ability to reduce neuroinflammation and improve functions of the brain. Furthermore, it improves social anxiety, cognition, and repetitive behaviors.
Increase immunity: MSC restore the balance between immune response and improves immune dysregulation.
Enhance neural repair and growth: the improvement in neural repair automatically enhances cognitive functions like learning, memory, execution function and intelligence quotient (IQ).
Reduction in use of medications: Autism requires use of medications for a long period of time, this increases the risk of side effects. Therefore, MSCs offer a great alternative option for the treatment of ASD because of numerous benefits.
Long term effects: Medications should be taken daily and consistently for a longer period of time in order to achieve results. Whereas MSC need to be transplanted once and the effects are evident for a long period of time i.e. the benefits are long-lasting.

Conclusion

With the advancement in regenerative medicine, stem cells for autism treatment and specifically MSC offers a new hope. Above all, the ability to migrate to the site of repair and regenerate the tissue by modulating immune system is one of the highlights of the MSC. Particularly, in ASD, mesenchymal stem cells improve social skills, cognition, communication skills and repetitive behavior.

In patients with ASD, MSCs pose the ability to reduce neuroinflammation and enhance functions of the brain. Therefore, MSC treatment in gaining popularity in ASD due to its potential benefits.

FAQ’s

Q: What is autism and how many people does it affect?

Autism is a neurodevelopmental disorder that affects a person’s social communication and interaction and shows repetitive patterns or behavior. Moreover, autism is a subgroup of autism spectrum disorder. Above all, a recent study related to ASD reports that globally around 61.8 million people are affected with ASD.

Q: When did the MSC originate?

In the 1960s, Alexander Friedenstein uncovered that bone marrow is not only a source of hemopoietic stem cells but also contains cells which originate from mesenchyme. So in the year 1991, Kaplan suggested that the cells that originate from mesenchyme region be named as mesenchymal stem cells. Hence, since 1991, the cells from mesenchyme origin are labelled as mesenchymal stem cells.

Q: What are the benefits of MSCs?

The benefits of MSC are improvement in cognition, social skills and communication, and reduction in neuroinflammation. Additionally, it also increase immunity enhance neural repair and growth.

Q: How does MSC work on immune system?

MSCs have the ability to restore immune balance by increasing the levels of IL-10 and IL-4 levels and reducing levels of TNF-α, IL-1β and IFN-γ.

Role Of Mesenchymal Stem Cells (MSCs) In Autism Treatment