Cancer research has considerably progressed with the improvement of in vitro study models, helping to understand the key role of the tumor microenvironment in cancer development and progression. Over the last few years, complex 3D human cell culture systems have gained much popularity over in vivo models, as they accurately mimic the tumor microenvironment and allow high-throughput drug screening. Of particular interest, in vitrohuman 3D tissue constructs, produced by the self-assembly method of tissue engineering, have been successfully used to model the tumor microenvironment and now represent a very promising approach to further develop diverse cancer models. In this review, we describe the importance of the tumor microenvironment and present the existing in vitro cancer models generated through the self-assembly method of tissue engineering. Lastly, we highlight the relevance of this approach to mimic various and complex tumors, including basal cell carcinoma, cutaneous neurofibroma, skin melanoma, bladder cancer, and uveal melanoma.

Since the 1980s, deep and extensive skin wounds and burns are treated with autologous split-thickness skin grafts, or cultured epidermal autografts, when donor sites are limited. However, the clinical use of cultured epidermal autografts often remains unsatisfactory because of poor engraftment rates, altered wound healing, and reduced skin functionality. In the past few decades, mesenchymal stromal cells (MSCs) have raised much attention because of their anti-inflammatory, protrophic, and pro-remodeling capacities. More specifically, gingival MSCs have been shown to possess enhanced wound healing properties compared with other tissue sources. Growing evidence also indicates that MSC priming could potentiate therapeutic effects in diverse in vitro and in vivo models of skin trauma. In this study, we found that IL-1beprimed gingival MSCs promoted cell migration, dermal-epidermal junction formation, and inflammation reduction in vitro, as well as improved epidermal substitute engraftment in vivo. IL-1beprimed gingival MSCs had different secretory profiles from naive gingival MSCs, characterized by an overexpression of transforming growth factor-b and matrix metalloproteinase (MMP) pathway agonists. Eventually, MMP-1, MMP-9, and transforming growth factor-b1 appeared to be critically involved in IL-1beprimed gingival MSC mechanisms of action.

Human mesenchymal stromal cells (hMSCs) are adult-source cells that have been extensively evaluated for cell-based therapies. hMSCs delivered by intravascular injection have been reported to accumulate at the sites of injury to promote tissue repair and can also be employed as vectors for the delivery of therapeutic genes. However, the full potential of hMSCs remains limited as the cells are lost after injection due to anoikis and the adverse pathologic environment. Encapsulation of cells has been proposed as a means of increasing cell viability. However, controlling the release of therapeutic cells over time to target tissue still remains a challenge today. Here, we report the design and development of thermo-rheological responsive hydrogels that allow for precise, time dependent controlled-release of hMSCs. The encapsulated hMSCs retained good viability from 76% to 87% dependent upon the hydrogel compositions. We demonstrated the design of different blended hydrogel composites with modulated strength (S parameter) and looseness of hydrogel networks (N parameter) to control the release of hMSCs from thermo-responsive hydrogel capsules. We further showed the feasibility for controlled-release of encapsulated hMSCs within 3D matrix scaffolds. We reported for the first time by a systematic analysis that there is a direct correlation between the thermo-rheological properties associated with the degradation of the hydrogel composite and the cell release kinetics. This work therefore provides new insights into the further development of smart carrier systems for stem cell therapy.

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Over the last century, the clinical management of severe skin burns significantly progressed with the development of burn care units, topical antimicrobials, resuscitation methods, early eschar excision surgeries, and skin grafts. Despite these considerable advances, the present treatment of severe burns remains burdensome, and patients are highly susceptible to skin engraftment failure, infections, organ dysfunction, and hypertrophic scarring. Recent researches have focused on mesenchymal stromal cell (MSC) therapy and hold great promises for tissue repair, as reported in several animal studies and clinical cases. In the present review, we will provide an up-to-date outlook of the pathophysiology of severe skin burns, clinical treatment modalities and current limitations. We will then focus on MSCs and their potential in the burn wound healing both in in vitro and in vivo studies. A specific attention will be paid to the cell preconditioning approach, as a means of improving the MSC efficacy in the treatment of major skin burns. In particular, we will debate how several preconditioning cues would modulate the MSC properties to better match up with the burn pathophysiology in the course of the cell therapy. Finally, we will discuss the clinical interest and feasibility of a MSC-based therapy in comparison to their paracrine derivatives, including microvesicles and conditioned media for the treatment of major skin burn injuries.