Extracellular vesicles from hair follicle-derived mesenchymal stromal cells: isolation, characterization and therapeutic potential for chronic wound healing

[EN] Background Mesenchymal stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have demonstrated to elicit immunomodulatory and pro-regenerative properties that are beneficial for the treatment of chronic wounds. Thanks to different mediators, MSC-EVs have shown to play an important role in the proliferation, migration and cell survival of different skin cell populations. However, there is still a big bid to achieve the most effective, suitable and available source of MSC-EVs. Methods We isolated, characterized and compared medium-large EVs (m-lEVs) and small EVs (sEVs) obtained from hair follicle-derived MSCs (HF-MSCs) against the gold standard in regenerative medicine, EVs isolated from adipose tissue-derived MSCs (AT-MSCs). Results We demonstrated that HF-EVs, as well as AT-EVs, expressed typical MSC-EVs markers (CD9, CD44, CD63, CD81 and CD105) among other different functional markers. We showed that both cell types were able to increase human dermal fibroblasts (HDFs) proliferation and migration. Moreover, both MSC-EVs were able to increase angiogenesis in human umbilical vein endothelial cells (HUVECs) and protect HDFs exposed to a hyperglycemic environment from oxidative stress and cytotoxicity. Conclusions Taken together, HF-EVs demonstrated to exhibit comparable potential to that of AT-EVs as promising candidates in the treatment of chronic wounds.This research was funded by the Basque Government (Consolidated Groups, IT907-16 and PRE_2018_1_0412)

Green hemostatic sponge-like scaffold composed of soy protein and chitin for the treatment of epistaxis

Epistaxis is one of the most common otorhinolaryngology emergencies worldwide. Although there are currently several treatments available, they present several disadvantages. This, in addition to the increasing social need of being environmentally respectful, led us to investigate whether a sponge-like scaffold (SP-CH) produced from natural by-products of the food industry - soy protein and beta-chitin - can be employed as a nasal pack for the treatment of epistaxis. To evaluate the potential of our material as a nasal pack, it was compared with two of the most commonly used nasal packs in the clinic: a basic gauze and the gold standard Merocel. Our SP-CH presented great physicochemical and mechanical properties, lost weight in aqueous medium, and could even partially degrade when incubated in blood. It was shown to be both biocompatible and hemocompatible in vitro, clearing up any doubt about its safety. It showed increased blood clotting capacity in vitro, as well as increased capacity to bind both red blood cells and platelets, compared to the standard gauze and Merocel. Finally, a rat-tail amputation model revealed that our SP-CH could even reduce bleeding time in vivo. This work, carried out from a circular economy approach, demonstrates that a green strategy can be followed to manufacture nasal packs using valorized by-products of the food industry, with equal or even better hemostatic properties than the gold standard in the clinic.Authors thank Eusko Jaurlaritza (Grupos Consolidados, No ref: IT907-16) and MCI/AEI/FEDER, UE (RTI2018-097100-B-C22)

Mesenchymal stromal cells-based sustainable strategies for wound management: form valorized cell delivery systems to cell-free therapies

El capítulo 2 está sujeto a confidencialidad por el autor. 335 p.In this doctoral thesis, we aimed to develop a complete biomaterial, following a circular economy thinking, which can tackle multiple stages of the wound healing process. In this sense, we designed a sponge-like scaffold composed of soy protein and ß-chitin with hemostatic properties, which can be combined with mesenchymal stromal cells (MSCs), for treating different wounds. Thanks to their anti-inflammatory, immunomodulatory and proregenerative properties, the MSCs have demonstrated to be very effective for treating multiple pathologies. However, despite the use of MSCs combined with biomaterials holds a promising potential, in this work we aimed to explore also the extracelular vesicle fraction of the MSCs secretome. Thus, this cell-free alternative presents the advantages of being; more easily handled, characterized, standardized, stored and potentially safer than MSCs, while exhibiting also therapeutic properties