Stem Cell Blog

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A recent study, carried out both in vitro and in vivo on a mouse model, has found that extracellular vesicles derived from adipose (fat) and umbilical cord mesenchymal stem cells could have a regenerative effect on sun-damaged skin.[1]

Sun damage causes and consequences

Unprotected exposure to harmful ultraviolet (UV) rays from the sun damages the DNA in your skin, ageing it prematurely. This is called photoaging, or sun damage, and can take several forms:[2] [3] [4]

  • Wrinkles and skin thickening: UV rays break down collagen and elastin, proteins which give your skin its structure and elasticity. As a result, skin becomes thicker and wrinkled over time, beyond what would normally be caused by ageing.

  • Sun spots, redness or blotchiness: skin cells produce melanin as a reaction to UV rays, in an attempt to protect against further sun damage. This is the same process that gives you a tan. However, over time, the damaged skin becomes permanently, unevenly pigmented, causing darker patches often called sun spots. This can also take the form of broken blood vessels, causing permanent redness or blotchiness. This happens particularly in areas frequently exposed to the sun, such as the face and hands.

  • Skin cancer: too much UV exposure can cause skin cancer. In the UK, overexposure to UV radiation is the cause of 85% of cases of melanoma skin cancers.[5]

What are extracellular vesicles? 

Extracellular vesicles are tiny particles which are generated from cells. They can carry important biomolecules, like fats and proteins, to other cells, working as a messenger of sorts.

Because the contents of extracellular vesicles can vary depending on the originating cells, scientists believe they could be of great importance in medicine. They could serve as a prognostic tool to predict the likely course of diseases, as well as help to cure them.[6]

In particular, extracellular vesicles derived from mesenchymal stem cells could inherit their regenerative properties, and have been a recent focus of research for their therapeutic potential.

What did the study find?

In the study, scientists from Peking Union Medical College, Beijing, China, aimed to investigate the effects of extracellular vesicles derived from adipose mesenchymal stem cells (AMSC-EVs) and umbilical cord mesenchymal stem cells (HUMSC-EVs) on photoaging.

In vitro, AMSC-EVs and HUMSC-EVs had positive effects on keratinocytes (cells which make up the outermost layer of the skin) and fibroblasts (cells which make up the connective tissue in the middle layer of the skin) that had been exposed to UV radiation. Treatment with EVs lowered inflammation and reduced the levels at which various biomarkers of senescence (ageing) were present in cells. Moreover, the treatment boosted cell proliferation and migration, properties which make skin cells better able to heal damage. Similar protective and regenerative effects were also observed using an in-vitro, full-thickness model of human skin.

These positive results prompted further analysis in vivo, using nude mice. The mice were randomly split into four groups, keeping one as the control. The other three groups were first exposed to high doses of UV radiation, then treated, respectively, with phosphate-buffered saline (PBS) as a placebo, with AMSC-EVs and with HUMSC-EVs.

All three groups exposed to UV initially developed deep, wide wrinkles. By the end of the observation period, however, the skin of mice treated with EV showed significantly fewer and thinner wrinkles. Skin analysis showed that EV treatment helped the skin recover water content, and reversed the epidermal thickening caused by UV radiation. The treatment also improved collagen and elastin levels and reduced inflammation. Additionally, there were fewer biomarkers of ageing in the skin cells of treated mice.

The benefits of stem cell banking

Both types of EVs studied proved effective in mitigating photoaging. However, the researchers noted that, in the mouse model, the effects of EVs derived from umbilical cord MSCs seemed better, from a therapeutic point of view, than those of EVs derived from fat tissue MSCs. The skin of the mice in the HUMSC-EV treatment group was noticeably less wrinkled. Additionally, the skin’s water content was much closer to that of the mice who had not been exposed to UV radiation at all, as was the epidermal thickness.

Furthermore, the process of collecting fat tissue for therapies is inherently invasive, but must be undergone if patients wish to use autologous (their own) stem cells as a therapeutic source. Conversely, the collection of stem cells from the umbilical cord is a painless, entirely non-invasive process; however, the cord must have been collected immediately after birth, and the cells and tissues cryogenically stored for future use. If this was not done, the only way to access therapies based on umbilical cord stem cells is the use of allogeneic (donor) cords – something which can encounter any number of issues, from lack of availability to incompatibility or rejection.

To find out more about storing your baby’s umbilical cord stem cells, so they will have them ready and waiting rather than needing to seek out alternative stem cell sources should they ever need regenerative therapies, fill in the form below to request your welcome pack.

References

[1] Zhang, H., et al. (2024). Human adipose and umbilical cord mesenchymal stem cell-derived extracellular vesicles mitigate photoaging via TIMP1/Notch1. Signal Transduction and Targeted Therapy, 9(1). doi:https://doi.org/10.1038/s41392-024-01993-z

[2] Grabel, A. (2019). Photoaging: What You Need to Know About the Other Kind of Aging. The Skin Cancer Foundation. https://www.skincancer.org/blog/photoaging-what-you-need-to-know/

[3] Cleveland Clinic (2022). Sun-damaged Skin: Photoaging, Signs, Causes & Treatment.  https://my.clevelandclinic.org/health/diseases/5240-sun-damage-protecting-yourself

[4] Yale Medicine (2023). Photoaging (Sun Damage). https://www.yalemedicine.org/conditions/sun-damage

[5] Cancer Research UK (2020). Risks and causes of melanoma skin cancer. https://www.cancerresearchuk.org/about-cancer/melanoma/risks-causes

[6] Zhang, Y., Liu, Y., Liu, H. and Tang, W.H. (2019). Exosomes: biogenesis, biologic function and clinical potential. Cell & Bioscience, 9(1). doi:https://doi.org/10.1186/s13578-019-0282-2


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Recent research indicates that umbilical cord exosomes have huge potential in the field of regenerative medicine.

In this blog we’ll explore what exosomes are, where they’re found, and how they could be used in developing new, life changing therapies for a range of conditions.

What are exosomes?

Exosomes are nano-sized particles that contain key biomolecules like proteins and lipids and travel between cells like messengers, regulating numerous biological processes including inflammatory responses.

Initially thought to be responsible for conveying waste away from cells, in recent years numerous trials and studies have explored their intercellular communicatory function and the  potential this offers in a range of therapeutic applications.

Where are exosomes found?

Exosomes are produced by virtually every cell in the body, including stem cells.

Excitingly they can be derived from the mesenchymal stem cells that exist within both umbilical cord blood and umbilical cord tissue.

Due to the low immunogenicity (the likelihood of being attacked by the immune system when transplanted) of mesenchymal stem cells derived from the umbilical cord, along with their non-invasive harvest procedure and ease of expansion in vitro, umbilical cord MSC exosomes (UC-MSC-Exo) are well suited for research and potentially therapeutic purposes. [1]

What can umbilical cord exosomes do?

Below are a few examples of recent trials utilising UC-MSC-Exo in the treatment of various conditions.

Heal wounds and repair nerves

A 2022 study investigating the use of UC-MSC-Exo in treating cutaneous nerve damage and wound healing showed that exosomes have the ability to promote skin and nerve regeneration.

Studied in vitro, researchers found that UC-MSC-Exo promoted the migration and proliferation of skin fibroblasts – cells that play a key role in forming connective tissue.

Additionally, UC-MSC-Exo were also found to promote the secretion of nerve growth factors by fibroblasts, suggesting that exosomes may enhance wound healing by promoting nerve repair.

Tested in vivo in a mouse model, the study showed that the wounds of the treatment group who received UC-MSC-Exo healed faster than the wounds of the group who received a control medium.

The study concluded that UC-MSC-Exo produced therapeutic effects by promoting skin and nerve regeneration. [2]

Slow the progress of osteoarthritis

Another study from 2022 demonstrated that exosomes derived from the umbilical cord have the potential to be used as a treatment method for osteoarthritis (OA).

Using a rat model, researchers undertook a surgical procedure designed to recreate the effects of knee osteoarthritis. They then administered injections of either UC-MSC-Exo or saline solution. After 8 weeks, knee samples were taken to assess the progression of the disease.

Researchers discovered that in the knees of rats who had received injections of exosomes the progression of OA had been halted and severe damage to knee cartilage prevented.

One of the key reasons behind this, the researchers found, was that the exosomes promoted the migration and proliferation of chondrocytes – cells that make up cartilage. They also found that the exosomes helped to inhibit the secretion of pro-inflammatory factors, as well as regulate immune responses; contributing factors in cartilage regeneration. [3]

Alleviate liver damage and disease

A study from 2020 showed that exosomes derived from umbilical cord mesenchymal stem cells were able to secrete the molecule miR-455-3p which helped to suppress inflammatory immune responses and inhibit signalling pathways in order to improve liver damage. [4]

Another study showed that exosomes derived from umbilical cord mesenchymal stem cells have antioxidant effects.

A contributing factor to the progression of liver damage, oxidative stress occurs when there is an imbalance in free radicals (unstable oxygen molecules) and antioxidants in the liver. Oxidative stress can lead to what’s known as apoptosis – programmed cell death. [5]

By using a mouse model, researchers were able to ascertain that injections of UC-MSC-Exo inhibited apoptosis in liver injury, reversing the fallout from oxidative stress. [6]

Promote heart repair

There have been several studies indicating that exosomes derived from umbilical cord mesenchymal stem cells have the ability to reduce myocardial injury – damage to heart tissue.

A study from 2018 showed that UC-MSC-Exo may have the ability to promote the expression of Smad7, a protein which aids in myocardial protection by blocking certain signalling pathways.

Researchers believed this could be the mechanism underlying exosomes’ ability to inhibit apoptosis, promote angiogenesis (the formation of new blood vessels) and improve cardiac function following acute myocardial infarction. [7] [8]

Rejuvenate older stem cells

An especially intriguing study from 2020 also showed that exosomes derived from umbilical cord mesenchymal stem cells could help in myocardial repair by rejuvenating the activity and function of mesenchymal stem cells in older patients.

Because heart conditions mainly affect older patients, the risk of immunogenicity associated with allogeneic stem cell transplants in helping to treat heart damage is a potential risk. This leaves autologous stem cell transplants – using stem cells from the patient themselves – as an available treatment option. However, due to age and cardiovascular risk factors, these autologous stem cells can be limited in their usefulness.

What this study found, however, is that UC-MSC-Exo have the ability to ameliorate the senescence of older mesenchymal stem cells and renew their biological activity, such as the potential to differentiate into cartilage, bone, and fat cells.

In effect this means that umbilical cord exosomes could help in restoring the regenerative capacity of mesenchymal stem cells in a range of therapies for patients who need them most. [9]

Exosomes and cord blood banking

As some of these trials demonstrate, exosomes are a hugely exciting field of regenerative medicine, and their therapeutic potential is only just beginning to be understood.

Most exciting is that these exosomes can be found in umbilical cord blood and tissue which, although usually thrown away as medical waste, can be stored so that your baby has access to their own stem cells that they can use in future therapies.

To learn more about the potential of umbilical cord stem cells and exosomes, contact our specialist team on 01444 873 950 – they’ll be more than happy to help answer any questions you may have.

In the meantime, why not fill out your details below for a free Welcome Pack containing everything you need to know about storing stem cells for your baby.

References

[1] Zhang, N., Zhu, J., Ma, Q. et al. (2020) Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair. Stem Cell Res Ther 11, 273. https://doi.org/10.1186/s13287-020-01782-9

[2] Zhu, Z., Zhang, X., Hao, H., Xu, H., Shu, J., Hou, Q., & Wang, M. (2022). Exosomes Derived From Umbilical Cord Mesenchymal Stem Cells Treat Cutaneous Nerve Damage and Promote Wound Healing. Frontiers in cellular neuroscience, 16, 913009. https://doi.org/10.3389/fncel.2022.913009

[3] Li, P., Lv, S., Jiang, W., Si, L., Liao, B., Zhao, G., Xu, Z., Wang, L., Zhang, J., Wu, H., Peng, Q., Li, Z., Qi, L., Chi, G., & Li, Y. (2022). Exosomes derived from umbilical cord mesenchymal stem cells protect cartilage and regulate the polarization of macrophages in osteoarthritis. Annals of translational medicine, 10(18), 976. https://doi.org/10.21037/atm-22-3912

[4] Shao, M., Xu, Q., Wu, Z., Chen, Y., Shu, Y., Cao, X., Chen, M., Zhang, B., Zhou, Y., Yao, R., Shi, Y., & Bu, H. (2020). Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate IL-6-induced acute liver injury through miR-455-3p. Stem cell research & therapy, 11(1), 37. https://doi.org/10.1186/s13287-020-1550-0

[5] Li, S., Tan, H. Y., Wang, N., Zhang, Z. J., Lao, L., Wong, C. W., & Feng, Y. (2015). The Role of Oxidative Stress and Antioxidants in Liver Diseases. International journal of molecular sciences, 16(11), 26087–26124. https://doi.org/10.3390/ijms161125942

[6] Jiang, W., Tan, Y., Cai, M., Zhao, T., Mao, F., Zhang, X., Xu, W., Yan, Z., Qian, H., & Yan, Y. (2018). Human Umbilical Cord MSC-Derived Exosomes Suppress the Development of CCl4-Induced Liver Injury through Antioxidant Effect. Stem cells international, 2018, 6079642. https://doi.org/10.1155/2018/6079642

[7] Wang, X., Zhao, Y., Sun, L., Shi, Y., Li, Z., Zhao, X. … Zhu, W. (2018). Exosomes derived from human umbilical cord mesenchymal stem cells improve myocardial repair via upregulation of Smad7. International Journal of Molecular Medicine, 41, 3063-3072. https://doi.org/10.3892/ijmm.2018.3496

[8] Zhao, Yuanyuan, Sun, Xiaoxian, Cao, Wenming, Ma, Jie, Sun, Li, Qian, Hui, Zhu, Wei, Xu, Wenrong. (2015) Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury, Stem Cells International, 761643, 12 pages, 2015. https://doi.org/10.1155/2015/761643

[9] Zhang, N., Zhu, J., Ma, Q. et al. (2020) Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair. Stem Cell Res Ther 11, 273. https://doi.org/10.1186/s13287-020-01782-9