The Aesthetic Appointment Journal previously published this article by lymphoedema therapist Candice Kuschke about understanding lymphoedema and its management in South Africa. As someone experiencing secondary lymphoedema in my right foot and leg, which began five days before giving birth in 2022, I understand firsthand the challenges of managing this condition.
At first, I assumed it was normal pregnancy swelling, especially as my left foot showed only mild swelling, typical of pregnancy. However, three months postpartum, the oedema in my right foot began spreading to my calf and knee, increasing substantially to the point where I couldn’t fit into shoes. I underwent multiple ultrasounds to rule out thrombosis, consulted with three vascular surgeons, and had a CT scan to rule out any venous issues in the pelvis. Ultimately, after consulting with a trained lymphoedema physiotherapist and undergoing a lymphoscintigraphy, the diagnosis of lymphoedema was confirmed.
Following the diagnosis, I also consulted with a plastic surgeon experienced in lymphoedema surgery, including lymphaticovenous anastomosis (also referred to as lymphovenous bypass: LVA) and vascularised lymph node transfer (VLNT). I was not a candidate for surgery. Furthermore, the procedure is not covered by medical aid, is prohibitively expensive, and remains somewhat experimental, with some patients reporting less desirable outcomes.
There are two plastic surgeons I came across that offer these surgeries in Johannesburg, namely Dr Ben Moodie and Dr Dimitri Liakos.
Over the past two years, I’ve been undergoing all the traditional therapies – specialised manual lymphatic drainage (MLD), compression bandaging, a pneumatic compression device (used daily), exercise, nutrition, skincare, and more – to reduce and maintain the size of my limb. As well as some less traditional therapies – acupuncture, Chinese medicine, NIR Laser, LED body rolling, red light therapy, cryotherapy, and specialised supplements for lymphatic flow.
While these combined efforts have significantly reduced the limb size and improved my quality of life, wearing medical-grade compression toe caps and socks daily remains a crucial part of my maintenance routine.
Each article and description I read reiterated the same message: “There is no cure. It’s a ‘chronic condition’.” While I did my best to accept this reality, I couldn’t shake the feeling that there must be more that could be done – some avenues that need more exploration and attention. Adding to my frustration was the fact that my Discovery Health medical aid does not recognise lymphoedema as a chronic condition. This means that the necessary treatments, such as MLD and compression garments, which can cost over R5 000 for a single pair and need replacing every four to six months, quickly deplete medical savings. It’s disheartening, yet it fuels my determination to seek out other possibilities that might help those living with this condition.
My journey has led me to explore regenerative medicine in South Africa. Through extensive research, I’ve read various studies and treatment modalities from around the world, including autologous stem cell therapy. Based on this research, I have hypothesised that certain innovative approaches could complement traditional therapies in South Africa. While there are currently no definitive studies proving the absolute efficacy of these treatments for lymphoedema (or curing it), I believe they hold exciting potential and merit further investigation.
This might simply be the hopes and dreams of someone experiencing lymphoedema. But isn’t that where the most transformative ideas often begin – with a dream and a passion? Much like the dreamers and the “crazy ones” Steve Jobs famously celebrated, who dared to see the world not as it is, but as it could be, I approach this journey with curiosity and hope. I don’t claim to have the answers, nor do I believe that every innovation will succeed. But I do believe that progress is born from a willingness to challenge the status quo, to question what is, and to imagine what could be.
Below, I share my personal insights on some therapies that, if studied further, might offer additional support for individuals managing lymphoedema. My hope is to spark curiosity and inspire further exploration – not just for myself but for anyone navigating this journey and those helping to treat patients on the journey. After all, every breakthrough begins with daring to dream.
Please note: I am not a medical doctor. I am a journalist. The below does not replace the advice, guidance, and consultation with your practitioner.
1. The potential role of biomimetic human growth factors and exosomes
I’m combining these two under one header because growth factors and exosomes share similarities in their roles in cell communication and tissue regeneration, but they function differently and have distinct properties.
Here’s a comparison:
Growth factors
- Definition: Growth factors are proteins that act as chemical messengers, signalling cells to perform specific actions like growth, division, or repair.
- Mechanism: They bind to specific receptors on cell surfaces, activating pathways that regulate cellular behaviour (e.g. collagen production, wound healing, or cell differentiation).
- Production: They can be naturally derived from human cells (not legal in most countries) or synthetically created using biomimetic technology.
- Applications: Commonly used in regenerative medicine, skincare (e.g. anti-ageing serums), hair rejuvenation, and wound healing. They are often included in products like those from AQ Skin Solutions to stimulate the skin’s repair processes.
- Limitations: Growth factors act locally and require proper delivery systems to target specific areas.
Exosomes
- Definition: Exosomes are extracellular vesicles (tiny particles) secreted by cells, containing bioactive molecules like proteins, lipids, and various types of RNA, including mRNA, miRNA (microRNA), and other forms of non-coding RNA.
- Mechanism: They serve as delivery systems for their cargo, influencing the behaviour of recipient cells by transferring genetic material and proteins.
- Production: Naturally released by various cells, including stem cells. They can also be isolated and concentrated for therapeutic purposes.
- Applications: Used in cutting-edge regenerative therapies for skin, hair, and wound care, exosomes can help modulate inflammation, promote cell proliferation, and enhance tissue regeneration.
- Advantages: Exosomes offer a broader range of effects since they carry a complex mix of signalling molecules, which can target multiple pathways.
- Limitations: Their effects could depend on the cell source (human vs biomimetic vs plant-derived), and regulatory challenges exist in standardising certain exosome therapies. It should be noted that human-derived exosomes in products are not legal in almost all countries. In South Africa, we currently have biomimetic and plant-derived exosome products.
- Additionally, the groundbreaking Nobel-Prize-winning discovery of microRNA (miRNA) has opened new possibilities for treating lymphoedema, particularly through exosomes, which are rich in miRNA. This study highlights a potential future therapeutic approach, as miRNA and messenger RNA (mRNA) are closely interconnected. miRNA, a small non-coding RNA molecule, regulates gene expression by binding to mRNA, which serves as a copy of a gene’s DNA sequence in RNA form. This relationship demonstrates the potential of leveraging miRNA’s regulatory functions for innovative treatments. (For further details, refer to this study: PMC8187400.)
Exosomes also contain growth factors in addition to lipids, proteins, and mRNA. In fact, most of the proteins in exosomes are growth factors. In other words, exosomes are pockets of GFs (growth factors), but because of the RNA, they also have longer-lasting epigenetic effects.
Key differences
| Feature | Growth factors | Exosomes |
|---|---|---|
| Nature | Proteins | Skincare, hair, wound healing |
| Function | Specific signalling to cells | Multimodal signalling via cargo delivery |
| Targeting | Specific receptors on cells | Broader influence on multiple pathways |
| Stability | Less stable (prone to degradation) | More stable (protected cargo) |
| Applications | Skincare, hair, wound healing | Advanced regenerative medicine |
| Regulation | Established in skincare | Emerging and less standardised |
While both promote regeneration, growth factors are simpler in function and directly signal specific actions, whereas exosomes act as carriers of complex messages, influencing broader cellular processes. This makes exosomes potentially more versatile, but also more complex to regulate and standardise.
Growth factors and exosomes may both have a role in addressing fibrosis caused by lymphoedema, supporting lymphatic function and lymphangiogenesis (the process of new lymphatic vessels forming). While research in this area is still emerging, these factors could help by:
- Stimulating collagen production: Encouraging new collagen formation might improve skin elasticity and reduce the fibrotic texture common in affected areas.
- Supporting lymphatic vessel function: Some studies suggest that growth factors may enhance the health of lymphatic endothelial cells, potentially aiding lymphatic drainage.
- Promoting healing: By accelerating tissue repair, growth factors might improve the integrity and function of the skin and underlying lymphatic structures.
Growth factors and exosomes are applied topically following procedures such as skin needling or stamping to enhance their absorption and efficacy. Subdermal injections and intravenous (IV) therapies involving these technologies are not performed in South Africa (or in most countries); they remain off-label and require further research to establish their safety and efficacy.
2. Microneedling (Dermapen®) as a supportive modality
Microneedling involves creating controlled micro-injuries in the skin, triggering the body’s natural healing response. When paired with growth factors or exosomes, it could offer synergistic benefits:
- Breaking down fibrotic tissue: Microneedling may help remodel collagen and elastin, softening fibrosis in the affected areas.
- Improving skin texture: Stimulating new cell turnover could enhance skin elasticity and appearance.
- Increasing absorption of topical treatments: The micro-channels created by microneedling may improve the penetration of growth factors, exosomes, or other active ingredients, potentially boosting their effects.
3. Stem cell therapy
Autologous adipose/fat-derived stem cell therapy, which utilises a patient’s own stem cells and mesenchymal (bone marrow-derived) stem cells, as well as other cells, has emerged as a potential treatment for secondary lymphoedema. A systematic review and meta-analysis of both preclinical and clinical studies indicated that cell-based therapies could positively impact disease outcomes such as oedema reduction, increased density of lymphatic capillaries, improved lymphatic flow, lymphangiogenesis (formation of new lymphatic vessels), and decreased tissue fibrosis.
However, the underlying mechanisms remain unclear, and the heterogeneity among studies indicates the necessity for further randomised, controlled, and blinded research to validate the efficacy and safety of these novel treatments in clinical practice.
If you’re wondering what heterogeneity is, it refers to variation or diversity within a group, system, or study. In the context of scientific research, there are differences in the methods, participants, treatments, or outcomes across studies. This variation can make it challenging to draw definitive conclusions because the results might not be directly comparable or consistent.
For example, in studies on autologous stem cell therapy for lymphoedema, heterogeneity might include differences in:
- The type of stem cells used (e.g. adipose/fat-derived, mesenchymal/bone marrow-derived).
- The method of delivery (e.g. injection, IV, topical application).
- Patient demographics (e.g. age, health status, severity of lymphoedema).
- Outcome measurements (e.g. lymphatic flow, tissue fibrosis).
Addressing heterogeneity often requires larger, well-controlled studies to ensure consistent and reliable findings. However, these studies can be costly, and funding can be challenging, especially given the perception that lymphoedema is a relatively niche condition.
That said, the most recent estimates suggest that lymphoedema affects over 250 million people worldwide, warranting the need for greater investment and research into this condition. According to a CANSA paper from 2021, it’s estimated that 1–2% of the population in South Africa is affected by lymphoedema – meaning between 580 000 and 1 160 000 people may be living with it locally, or roughly 1 in every 50 to 100 people.
A good resource to explore is the Stem Cell Institute of South Africa. That said, I’ve yet to find definitive local feedback or clinical outcomes specifically relating to stem cell therapy for lymphoedema patients in South Africa, which again points to the need for more targeted research in this area.
4. Platelet-rich plasma (PRP), lymphocytes, and platelet-rich fibrin (PRF)
In addition to stem cell therapies, other regenerative approaches like PRP and lymphocytes are showing promising potential in addressing the challenges of lymphoedema.
Emerging research suggests that PRP and lymphocytes could play a significant role in managing lymphoedema. PRP, derived from the patient’s own blood, is a concentration of platelets that releases growth factors and cytokines, promoting tissue repair and regeneration. When used in lymphoedema, PRP has shown the potential to reduce fibrosis and stimulate the formation of new lymphatic vessels (lymphangiogenesis).
This approach can enhance lymphatic drainage, addressing the underlying issues associated with fluid accumulation and tissue damage. Additionally, lymphocytes, which are a type of white blood cell, are believed to contribute to tissue healing by regulating immune responses and combating inflammation.
Studies have demonstrated that the injection of PRP enriched with lymphocytes can synergistically improve lymphatic function, offering a promising avenue for integrative lymphoedema treatment.
While PRP and lymphocyte therapies remain experimental in this context, the minimal risk of adverse reactions due to their autologous nature (derived from the patient’s own body) makes them an attractive option for future research. As scientists continue to explore their potential, these therapies could complement traditional treatments and offer renewed hope for individuals managing this chronic condition.
PRF
Closely related to PRP is PRF, a second-generation autologous blood concentrate that contains platelets, leukocytes, and a fibrin matrix, offering a slower and more sustained release of growth factors compared to PRP. Unlike PRP, PRF does not require anticoagulants or synthetic additives, making it a more natural option for regenerative therapies.
Early evidence suggests PRF may support soft tissue healing and angiogenesis, and its ability to promote a prolonged healing response could make it particularly relevant in addressing the chronic inflammation and fibrosis seen in lymphoedema.
5. Carboxytherapy in lymphoedema management
Let’s not forget the golden oldie and the reemergence of a well-known therapy for lymphedema that was introduced to me by Dr Debbie Norval, who shared this study with me.
It has been a promising treatment for lymphoedema and has been gaining more and more attention as a treatment that targets microcirculation and lymphatic function.
Carboxytherapy, the therapeutic use of carbon dioxide (CO2), is an innovative approach for lymphoedema treatment. By injecting CO2 into affected tissues, this therapy enhances microcirculation and stimulates lymphatic drainage. CO2 works by relaxing smooth muscle cells in the walls of blood vessels, leading to improved blood flow velocity and oxygen delivery to tissues. This vasodilatory effect also helps reduce fibrosis and increase tissue elasticity.
Moreover, studies using lymphoscintigraphy, a type of imaging for lymphatic function, have shown that carboxytherapy can significantly decrease lymphatic stasis (build-up of fluid) and improve the physiological drainage of lymph fluid.
Clinical evidence indicates that carboxytherapy can result in measurable reductions in limb volume and circumference for patients with severe lymphoedema. This non-invasive treatment not only restores microcirculatory function but also serves as a supportive modality to traditional lymphoedema management strategies like compression therapy and manual drainage.
As research in this area evolves, carboxytherapy is solidifying its place as a valuable tool in comprehensive lymphoedema care.
In my case, addressing lymphoedema in the foot
The foot, often affected by lymphoedema-related fibrosis, presents unique challenges due to its lower density of lymphatic vessels. Treatments focused on improving the tissue health in this area could help to:
- Reduce the risk of further complications, such as additional fibrosis.
- Enhance lymphatic drainage, supporting better management of swelling and discomfort.
Synergistic potential with traditional therapies
While some of these regenerative approaches are still theoretical in this context, they might work well alongside traditional treatments like:
- Compression garments: Supporting mechanical drainage of fluid.
- Manual lymphatic drainage: Improving overall fluid movement in the body.
- Supplements and lifestyle adjustments: Reducing systemic inflammation and creating an environment more conducive to healing.
Could these approaches contribute to recovery?
Although these treatments may not yet offer a definitive resolution for lymphoedema, they hold significant promise as part of a comprehensive management strategy. By addressing fibrosis and supporting lymphatic function, these approaches could contribute to improved outcomes and enhanced quality of life for individuals living with this condition. Further research and clinical trials will be essential to fully understand their potential and integrate them into evidence-based care.
My thoughts
It’s important to note that I am not a doctor and cannot provide medical advice. These are personal hypotheses based on my own experiences and research, and they are shared to spark curiosity and conversation.
Current evidence for the efficacy of these regenerative treatments in lymphoedema management is limited, but I believe their potential warrants further study and investment.
I hope that by shedding light on these ideas, more attention can be drawn to the possibilities of combining traditional and cutting-edge therapies for conditions like lymphoedema.
For those managing this condition, these potential advancements could offer new avenues of hope and healing, not only for patients but for practitioners, too. Together, we can work toward advancing the understanding and management of lymphoedema for all those affected.
In closing
Regenerative medicine represents an exciting frontier in the management of lymphoedema, offering the potential not only to heal damaged tissues but also to stimulate the growth of new lymphatic vessels—a process known as lymphangiogenesis.
This is particularly significant because, unlike blood vessels, which can form collateral circulation, the lymphatic system has a much more limited ability to repair itself once damaged. For lymphoedema patients, regenerating new lymphatic pathways is the key to improving fluid drainage, reducing fibrosis, and ultimately enhancing long-term outcomes.
Emerging therapies such as biomimetic growth factors, exosome-based treatments, platelet-rich plasma (PRP), and stem cell applications are showing promise in this field. These treatments could play a role in stimulating the lymphatic endothelial cells, which line the lymphatic vessels, promoting tissue regeneration and potentially restoring proper lymphatic function over time. Additionally, techniques such as microneedling, red light therapy, and carboxytherapy may work synergistically by improving local circulation, reducing inflammation, and encouraging lymphatic flow.
While research is still in its early stages, these regenerative treatments may offer a complementary approach to traditional lymphoedema management rather than replacing existing strategies like manual lymphatic drainage (MLD), compression therapy, and skincare. By integrating cutting-edge regenerative medicine with proven conservative treatments, we may begin to shift the narrative from mere symptom control toward true tissue repair and functional recovery.
As with any medical intervention, it is crucial for patients to consult with a qualified plastic surgeon, regenerative medicine expert, dermatologist, lymphoedema therapist, or general practitioner before considering these treatments. Understanding the latest advancements and engaging with knowledgeable professionals will help ensure that patients receive safe, evidence-based care.
If you are a regenerative medicine practitioner, researcher, or lymphoedema therapist working with any of these modalities, we’d love to hear from you. Email info@aestheticappointment.co.za to share your insights or experiences.
References:
Here is the list of articles and studies I discovered before and while writing this article:
- https://www.embopress.org/doi/full/10.1038/s44321-023-00017-7 (Delivering Apelin and VEGF-C mRNA together)
- https://flashbiosolutions.com/blog/regenerative-medicine/ (Lymphedema treatment using FlashRNA® multi-RNA delivery technology)
- https://theralymph-europe.eu (Theralymph project website)
Rochelle is the founder and driving force behind Aesthetic Appointment. With a passion for the aesthetics and pro-ageing industry in South Africa, she has been in the aesthetic publishing industry since 2012, dedicated to creating a valuable platform for insights and knowledge, bridging the gap between patients and doctors - delivering reliable, medical-based information. Rochelle firmly believes in the power of a good skincare regimen, especially when started at home, and is committed to educating consumers about the myriad of treatments, procedures, and products available to them.
- Rochelle Friedmanhttps://www.aestheticappointment.co.za/author/rochelle
- Rochelle Friedmanhttps://www.aestheticappointment.co.za/author/rochelle
- Rochelle Friedmanhttps://www.aestheticappointment.co.za/author/rochelle
- Rochelle Friedmanhttps://www.aestheticappointment.co.za/author/rochelle
