Under the microscope: the potential of extracellular vesicles in diabetic wound healing

Dr Darius Widera and his research group at Reading University are studying the potential of readily accessible adult stem cells to improve symptoms of different degenerative disorders and diseases. At the moment, they are investigating extracellular vesicles (EVs) released by adult stem cells and trying to find out what their role is in diabetic wound healing. GrowDex® hydrogel has proved to be an easy-to-handle, animal-free matrix, for expansion of adult stem cells and generation of EVs. 

Stem cells serve as a limitless internal repair system in the human body, which is why scientists have been studying their unique properties and their potential role in patient care for decades. Adult stem cells are a pivotal tool within modern translational and regenerative medicine, and they have high potential to support the patients’ intrinsic ability to regenerate without risks and ethical concerns associated with embryonic stem cells. Lately, extracellular vesicles released by adult stem cells have been gaining significant interest in the research community. EVs seem to play a role in coagulation, and intercellular signalling. Their therapeutic use would further minimize risks and help to design cost-effective and ethical cell-based therapies.

Dr Darius Widera is an expert in stem cell biology and regenerative medicine. With a background in biochemistry, he works as a Lecturer (Assistant Professor) in Stem Cell Biology and Regenerative Medicine at the University of Reading, UK. The Widera Lab has over a decade of experience in the fields of adult stem cells, inflammatory signalling cascades in health and disease, and novel methods for clinical grade 3D-cultivation of human stem cells. In the recent years, the secretome of adult stem cells and extracellular vesicles have become new focal points of the lab.

“We are studying the potential of readily accessible adult stem cells to improve symptoms of different degenerative disorders and diseases, especially in cases where conventional treatment options fail to provide satisfactory results. We want to know how to improve the therapeutic results after application of these cells and would like to explore if substances they release could replace stem cell therapy,” Dr Widera explains.

The lab’s researchers are studying the impact of these promising therapeutic biologics in osteoporotic bone fractures, chronic obstructive pulmonary disease, and diabetic wound healing. They are also developing state-of-the art cell-based screening assays allowing fast and reproducible assessment of the regenerative potential of EVs and exploring their mode-of-action. Moreover, the lab is studying the influence of inflammation on the intrinsic potential of the body to regenerate itself. 

Dr Darius Widera (third on the left) and his research team. 

Extracellular vesicles can improve diabetic wound healing 

Diabetes mellitus is a major public health concern. In this context, diabetic foot ulcers are the most common reasons for hospitalisation among diabetics. In such ulcers, defective sense of touch, wound healing defects and impaired blood flow can lead to bacterial infections, where lower limb amputation represents the last therapeutic option. Importantly, many aspects of these complications are associated with ongoing inflammation and their treatment with stem cells is currently being explored in clinical trials. However, stem cell therapy is still highly experimental and – at least at its current stage – expensive, which reduces its potential impact.

Recent lines of evidence suggest that extracellular vesicles released by human adult stem cells harbour a regenerative potential that is comparable to adult stem cells – without the associated risks. At the moment, Dr Widera and his research team are participating in a collaborative project aiming to evaluate different protocols to isolate the most potent extracellular vesicles that can improve diabetic wound healing. 

“One of the biggest challenges of regenerative medicine is the translation of the results generated in a dish into clinically-compliant protocols. To achieve this, animal component-free and clinical-grade components must be used. However, especially in the 3D cell culture field, there is a lack of such consumables and reagents,“ Dr Widera says.

GrowDex®: animal-free, no air bubbles, easy to handle

Dr Widera’s team has long-lasting expertise in 3D cell culture including clinical grade human blood plasma-based hydrogels. The team is using GrowDex hydrogel for expansion of adult stem cells and generation of EVs. 

Due to the nature of their research, the hydrogels Dr Widera’s team needed to apply had to be free of animal-derived components to ensure an easy translation into a clinical grade product. For the same reason, batch-to-batch variability needed to be as low as possible. Finally, the 3D hydrogel had to be easy to handle, even by non-expert personnel. 

 “In our hands, GrowDex showed excellent batch-to-batch consistency and was easy to handle, especially since no cross-linking is required. In my opinion, a clear strength of GrowDex is that it has lower tendency than other hydrogels to produce air bubbles, which would negatively influence cell viability and result in heterogeneity of the gel.”

Dr Widera would clearly recommend GrowDex for EV generation for two particular reasons. 

“Firstly, stem cell culture in GrowDex allows a significant cost reduction as 3D cell culture allows higher cell numbers per volume of cell culture medium. Secondly, as GrowDex is free of animal-derived components, it would allow an easier translation into clinical practice at a later stage.”