One of the most critical processes in endometriosis is the formation of new blood vessels, which allows abnormal tissue to grow and become inflamed. This process is called angiogenesis. Inhibiting the formation of blood vessels can therefore be of paramount importance in the treatment of the disease. A recent study may now offer a revolutionary solution to this problem by creating genetically modified stem cells that produce a specific protein, endostatin.
Mesenchymal stem cells (MSCs) have been investigated as a promising option for cell therapy, but the effect and mechanism of action of endostatin-expressing endometrial MSCs (EMSCs) in endometriosis has been unclear. In this study, EMSCs cells were genetically engineered to overproduce endostatin (EMSCs-Endo). The researchers isolated endometrial mesenchymal stem cells and engineered them to produce endostatin, one of the most potent natural inhibitors of angiogenesis. The resulting cells were named EMSCs-Endo.
In in vitro studies, it was observed that EMSCs-Endo treatment reduced the angiogenic capacity of HUVEC cells (human umbilical vein endothelial cells). In in vivo experiments, EMSCs-Endo significantly inhibited the growth of endometriotic lesions. Endostatin not only prevents the formation of blood vessels but also inhibits the inflammatory processes responsible for the progression of the disease.
The results of the research are very promising. In in vitro (laboratory) experiments, EMSCs-Endo cells have successfully reduced the proliferation and migration of human umbilical vein endothelial cells, which are the essential building blocks of new blood vessels. And in animal studies, it was observed that the stem cells not only reduced the size of lesions, but also reduced the density of the vascular network in the affected areas. These effects are achieved by modifying the miRNA-21-5p/TIMP3/PI3K/Akt/mTOR signalling pathway. This pathway plays a key role in the regulation of angiogenesis, and the researchers found that endostatin-producing cells significantly reduced the intensity of this process. After treatment with EMSCs-Endo, levels of miRNA-21-5p, as well as p-PI3K, p-mTOR and p-Akt, were significantly reduced in HUVEC cells and mouse endometriotic lesions, while TIMP3 expression was significantly increased.
The safety results are also encouraging. No malignant lesions or other harmful or unpleasant side effects were observed in animal studies, which justifies our hope that the use of EMSCs-Endo cells will not only be effective but also safe in women with endometriosis.
This approach could be a major step forward in the treatment of endometriosis, especially for those for whom traditional therapies such as surgery or hormonal treatments do not produce lasting results or have serious side effects - so let's face it, pretty much everyone. Endostatin-expressing stem cells offer the possibility to target and effectively treat the disease while minimising the adverse effects on the body as a whole.
The research also highlights that the inhibition of angiogenesis may play a key role not only in halting disease progression but also in alleviating inflammation. In contrast to current methods of treating endometriosis, this new therapeutic approach may not only alleviate symptoms, but also address the underlying causes of the disease and the factors that promote its progression.
This breakthrough could not only shape the future of endometriosis treatment, but also open up new avenues for the treatment of other vascular diseases, such as benign and malignant tumours or chronic inflammation. Such a combination of endostatin and stem cell applications could revolutionise disease treatment and bring us one step closer to more effective and patient-centred medicine.
In conclusion, targeted gene therapy with EMSCs-Endo appears to be feasible, with efficacy due to inhibition of angiogenesis, suggesting that EMSCs are a promising tool for targeted gene therapies.
Source : https://pubmed.ncbi.nlm.nih.gov/39589222/
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