Stem Cell Therapy For Spinal Cord Injury: Hope For Paralyzed Patients

Spinal cord injury (SCI) primarily caused due to injury leads to loss of motor and sensory function. Generally, it mainly affects the spinal cord region often leading to loss of sensation and movement and paralysis. Globally, per million there are about 23 cases of spinal cord injury.

Classification of spinal cord injury is based on etiology

1. Almost 80% of the cases arise due to inflammatory, traumatic or congenital abnormalities.
2. However, in case of traumatic spinal cord injury, the falls constitute for 54.2%, accidents constitute for 37%, contusions constitute for 5.3% and recreational activities and sports injuries constitute for 3.5%.

Firstly, due to spinal cord injury, the spinal cord suffers from contusion and compression and secondly due to SCI, the patient experiences inflammation, edema, release of oxygen radical species, necrosis and cell death. Lastly, all of these together trigger inflammation and immune response.

Conventional and supportive management therapies:

Generally, the first step in the management of traumatic spinal cord injury is to provide rehabilitation and prevent the body from further damage i.e. neuroprotection.

1. Neuroprotection: clinicians recommend NSAID’s to suppress the immune system and inflammatory response. Eg: minocycline and cyclosporine.
2. In some cases, the healthcare provider also recommends the use of short term corticosteroids to prevent further deterioration.
3. Newest therapies that provide neuroprotection are riluzole, polyethylene glycol and that promote neurogeneration are chondroitinase, Rho inhibitors and stem cell therapy.
4. The American Association of Neurological Surgeons (AANS) guidelines suggest doctors to maintain the mean arterial pressure above 85mmhg to avoid worsening of neurological status.
5. Surgical treatment: surgical decompression is the best option that provides stability and promotes neurological recovery.

Stem cell therapy In Spinal Cord Injuries:

Current treatment therapy is only helpful in managing the symptoms and but these therapies are limited in efficacy. And the patient is required to undergo painful surgery which restricts his movement. In such cases, stem cell therapy is an excellent treatment option in spinal cord injuries. Moreover, the stem cells regenerate and differentiate, and provide neuroprotection, promotes regeneration of axons and has immunomodulatory and anti-inflammatory properties.     

Types of stem cells

The various types of stem cells for the stem cell therapy in SCI are:

1. Neural progenitor cells: these cells differentiate into astrocytes, neuronal cells and oligodendrocytes. The main function of these cells is that it enhances survival of neurons by promoting neuron differentiation and secreting growth factors. This restores motor and sensory functions.
2. Mesenchymal stem cells: The ideal property of mesenchymal stem cells is that promotes neuron differentiation and axon regeneration. The use of mesenchymal stem cells has several advantages like it is easy to isolate and has great differentiation capacity. There are different sources from where MSC’s can be derived. Some of the most common ones are: 
3. Bone marrow derived mesenchymal stem cells: Researchers obtain these stem cells from bone marrow and when they introduce these stem cells they migrate to the site of action and promote axon regeneration and reduce inflammatory response.
4. Umbilical cord derived mesenchymal stem cells: These stem cells reduce apoptosis and ischemia and improve motor functions. Researchers derive these stem cells from umbilical cord blood.
5. Adipose tissue derived mesenchymal stem cells: stem cells from adipose tissue regenerates neurons, promotes angiogenesis and stimulate anti-inflammation by releasing anti-inflammatory factors.

Mesenchymal stem cells functions:

The functions of mesenchymal stem cells specifically in the spinal cord injury are:

1. Mesenchymal stem cells in SCI reduce inflammatory levels of interleukin 7, IFN-γ and TNF-α.
2. In addition, they also increase anti-inflammatory levels of interleukin 4, 13 and macrophages. Thus, this promotes anti-inflammation.
3. Above all, MSC reduce necrosis and increase motor functions.

In the spinal cord injury, mesenchymal stem cells show various functions like neuroprotection, regeneration, immunomodulation and anti-inflammation.

Neuroprotective and regenerative function:

MSC enhance survival of neurons and regenerate axons by secreting number of factors.

1. Brain-derived neurotrophic factor (BDNF): increase longevity of neurons and enhance differentiation of neurons.
2. Glial cell line-derived neurotrophic factor (GDNF): enhances motor neuron survival and regeneration of axons and neurons.
3. Vascular endothelial growth factor (VEGF): this factor enhances tissue repair by enhancing angiogenesis.
4. Insulin-like growth factor-1: increases neuron survival and differentiation and promotes growth of axons.
5. Hepatocyte growth factor: provides neuroprotection and promote angiogenesis.
6. TGF-β: repairs tissue and shows immunomodulatory properties.

Immunomodulation and anti-inflammatory function:

• MSC exhibit immunomodulation by releasing IL-10, PGE2 and TGF-β which inhibits activation and differentiation of macrophages and T cells.
• Moreover, MSC also enhance survival and proliferation of neural stem cells oligodendrocyte precursor cells which repairs and regenerates tissue and exhibit immunomodulation.

Role of mesenchymal stem cell (MSC) derived exosomes in spinal cord injury:

1. MSC exosomes migrate to the site of injury and promote release of M2 macrophages which reduce inflammation.
2. Enhances recovery and reduce severity of injury.
3. Exosomes protect and regulate neuronal cell differentiation.
4. MSC derived exosomes also promote angiogenesis and axon regeneration.

Advantages of stem cell therapy:

• Stem cells have the ability to differentiate into neurons and glial cells.
• Because of the differentiation potential it can improve inflammation, motor functions and provide stability.

Spinal Cord Injury Patient Stories

• The benefit of mesenchymal stem cell therapy is that it is has excellent regeneration capacity and is ethically acceptable.
• The procedure is minimally invasive and shows fast recovery.

Challenges in stem cell therapy:

• • In cases where we employ embryonic stem cells, the risk for immune rejection and ethical issues rises. Another disadvantage is ability of cells to form tumor.
  • Timing of stem cell therapy, choice or the type of stem cells is another challenge as it has a direct impact on outcome of the therapy.

Cost and access to stem cell therapy also possess challenges in many ways.

Nanozymes:

• It is a novel enzymatic therapy made with addition of Mn3O4 and IRF-5SiRNA. 
• The main function of this novel therapy is to exhibit anti-inflammatory and antioxidant effect. 
• The nanozymes release 02 which are essential to reduce oxidative stress and enhance angiogenesis.
• The nanozymes also enhance proliferation and regeneration of neurons and increases motor functions.

Evidence based studies providing hope for paralysis patient:

According to a phase 1 clinical trial study by researchers from mayo clinic, adipose tissue derived mesenchymal stem cells are safe in patients and improve various function in patients with spinal cord injury. The patients show improvement in sensation and muscle strength i.e. movement which provides a new hope for paralysis patients. They also improve sensory and motor functions.

Conclusion

Based on the multiple studies in the field of regenerative medicine, Spinal cord injury can be efficiently managed using stem cells and exosomes. Generally, the research findings suggest that the stem cell therapy has the ability to regenerate and repair the tissue and restore motor function in SCI. Furthermore, the overall treatment options not only restore normal function but also has the potential to improve patient quality of life.

Therefore, stem cell therapy promises to be the most important therapy in the treatment of spinal cord injury and it provides hope to multiple paralysis patients.

FAQ’s

Q: Define spinal cord injury?

Spinal cord injury is a life threatening neurodegenerative condition that primarily causes loss of motor and sensory function. Generally, it mainly affects the spinal cord region often leading to loss of sensation and movement and paralysis.

Q: What is the function of mesenchymal derived exosomes in spinal cord injury?

MSC exosomes migrate to the site of injury and promote release of M2 macrophages which reduce inflammation and enhance recovery and reduce severity of injury. Additionally, MSC derived exosomes also promote angiogenesis and axon regeneration.

Q: How does mesenchymal stem cell work in spinal cord injury?

Mesenchymal stem cells in SCI reduce inflammatory levels of interleukin 7, IFN-γ and TNF-α. In addition, they also increase anti-inflammatory levels of interleukin 4, 13 and macrophages. Thus, this promotes anti-inflammation. Above all, MSC reduce necrosis and increase motor functions.

Q: How does mesenchymal stem cells exhibit immunomodulation?

Mesenchymal stem cells exhibit immunomodulation by releasing IL-10, PGE2 and TGF-β which inhibits activation and differentiation of macrophages and T cells. Moreover, MSC also enhance survival and proliferation of neural stem cells oligodendrocyte precursor cells which repairs and regenerates tissue and exhibit immunomodulation.