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Adipose-Derived Regenerative Cell Therapy for Burn Wound Healing: A Comparison of Two Delivery Methods.

ABSTRACT: Objective: The use of noncultured autologous stromal vascular fraction or clinical grade adipose-derived regenerative cells (ADRCs) is a promising strategy to promote wound healing and tissue repair. Nevertheless, issues regarding the optimal mode of administration remain unclear. The purpose of this study was to compare the effects of local injection and topical spray delivery of ADRCs in a porcine model of thermal burns. Approach: Full-thickness thermal burns were created on the dorsum of 10 Gottingen minipigs. Two days following injury, wounds underwent fascial excision and were randomized to receive control vehicle or freshly isolated autologous ADRCs delivered by either multiple injections into or surrounding the wound bed, or by spray onto the wound surface (0.25?×?106 viable cells/cm2). Healing was evaluated by planimetry, histopathology, and immunohistochemistry at day 7, 12, 16, 21, and 28 posttreatment. Results:In vitro analysis demonstrated that there was no substantial loss of cell number or viability attributable to the spray procedure. Planimetric assessment revealed that delivery of ADRCs by either local injection or topical spray increased wound reepithelialization relative to control at day 14. No significant difference in wound reepithelialization was observed between both delivery approaches. In addition, on day 7 posttreatment, blood vessel density was greater in wounds receiving local or topical spray ADRCs than in the wounds treated with vehicle control. Histopathologic analysis suggests that ADRC treatment may modulate the inflammatory response by reducing neutrophil infiltration at day 7 and 12 posttreatment, irrespective of the route of administration. Conclusions: These data demonstrate that local injection and spray delivery of ADRCs modulate inflammation and improve wound angiogenesis and epithelialization. Importantly, both delivery routes exhibited similar effects on wound healing. Given the greater ease-of-use associated with topical spray delivery, these data support the use of a spray system for autologous ADRC delivery.

SUBMITTER: Foubert P

PROVIDER: S-EPMC4900222 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Adipose-Derived Regenerative Cell Therapy for Burn Wound Healing: A Comparison of Two Delivery Methods.

Foubert Philippe P Gonzalez Andreina D AD Teodosescu Stephan S Berard Felipe F Doyle-Eisele Melanie M Yekkala Krishna K Tenenhaus Mayer M Fraser John K JK

Advances in wound care 20160701 7

<b>Objective:</b> The use of noncultured autologous stromal vascular fraction or clinical grade adipose-derived regenerative cells (ADRCs) is a promising strategy to promote wound healing and tissue repair. Nevertheless, issues regarding the optimal mode of administration remain unclear. The purpose of this study was to compare the effects of local injection and topical spray delivery of ADRCs in a porcine model of thermal burns. <b>Approach:</b> Full-thickness thermal burns were created on the ...[more]

PMID: 27366590

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Project description:Adipose-derived stem cells (ADSCs) transplant has been reported to be a potential treatment for burn wounds. However, the effects of autogenicity and allogenicity of ADSCs on burn wound healing have not been investigated and the method for using ADSCs still needs to be established. This study compared the healing effects of autologous and allogenic ADSCs and determined an optimal method of using ADSCs to treat acute burn wounds. Experiments were performed in 20 male Wistar rats (weight, 176-250 g; age, 6-7 weeks). Two identical full-thickness burn wounds (radius, 4 mm) were created in each rat. ADSCs harvested from inguinal area and characterized by their high multipotency were injected into burn wounds in the original donor rats (autologous ADSCs group) or in other rats (allogenic ADSCs group). The injection site was either the wound center or the four corners 0.5 cm from the wound edge. The reduction of burn surface areas in the two experimental groups and in control group were evaluated with Image J software for 15 days post-wounding to determine the wound healing rates. Wound healing was significantly faster in the autologous ADSCs group compared to both the allogenic ADSCs group (p<0.05) and control group (p<0.05). Wound healing in the allogenic ADSC group did not significantly differ from that in control group. Notably, ADSC injections 0.5cm from the wound edge showed significantly improved healing compared to ADSCs injections in the wound center (p<0.05). This study demonstrated the therapeutic efficacy of ADSCs in treating acute burn wounds in rats. However, only autologous ADSCs improved healing in acute burn wounds; allogenic ADSCs did not. This study further determined a superior location of using ADSCs injections to treat burn wounds including the injection site. Future studies will replicate the experiment in a larger and long-term scale burn wounds in higher mammalian models to facilitate ADSCs therapy in burn wound clinical practice.

Project description:BackgroundStem cell therapies represent a promising tool in regenerative medicine. Considering the drawbacks of direct stem cell injections (e.g. poor cell localisation), extracellular matrix-based biomaterials (e.g. scaffolds and tissue grafts), due to their compositional biofunctionality and cytocompatibility, are under investigation as potential stem cell carriers.MethodsThe present study assessed the potential of three commercially available extracellular matrix-based biomaterials [a collagen/glycosaminoglycan scaffold (Integra™ Matrix Wound Dressing), a decellularised porcine peritoneum (XenoMEM™) and a porcine urinary bladder (MatriStem™)] as human adipose-derived stem cell delivery vehicles.ResultsBoth tissue grafts induced significantly (p < 0.01) higher human adipose-derived stem cell proliferation in vitro over the collagen scaffold, especially when the cells were seeded on the basement membrane side. Human adipose-derived stem cell phenotype and trilineage differentiation potential was preserved in all biomaterials. In a splinted wound healing nude mouse model, in comparison to sham, biomaterials alone and cells alone groups, all biomaterials seeded with human adipose-derived stem cells showed a moderate improvement of wound closure, a significantly (p < 0.05) lower wound gap and scar index and a significantly (p < 0.05) higher proportion of mature collagen deposition and angiogenesis (the highest, p < 0.01, was observed for the cell loaded at the basement membrane XenoMEM™ group). All cell-loaded biomaterial groups retained more cells at the implantation side than the direct injection group, even though they were loaded with half of the cells than the cell injection group.ConclusionsThis study further advocates the use of extracellular matrix-based biomaterials (in particular porcine peritoneum) as human adipose-derived stem cell delivery vehicles. Comparative analysis of a collagen scaffold (Integra™ Matrix Wound Dressing) and two tissue grafts [decellularised porcine peritoneum (XenoMEM™) and porcine urinary bladder (MatriStem™)] as human adipose-derived stem cells carriers.

Project description:Adipose mesenchymal stem cell (ADMSC)-derived exosomes (ADMSC-Exos) have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns. However, the low yield, easy loss after direct coating, and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing. And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques, especially in exosome-releasing hydrogel system. Therefore, we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing, namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid (HA). In this project, we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional (2D) plate culture (2D-Exos), microcarrier culture (2.5D-Exos), and 3D-printed microfiber culture (3D-Exos). Results showed that compared with 2D-Exos and 2.5D-Exos, 3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly. Additionally, 3D-Exos had stronger angiogenesis-promoting effects in tube formation of (HUVECs) cells. Moreover, we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos, including accelerated burn wound healing rate and better collagen remodeling. The study findings reveal that the HA-loaded, controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing, while concurrently introducing a facile application approach. This system markedly bolsters the exosomal loading efficiency, provides a robust protective milieu, and potentiates the inherent biological functionalities of the exosomes. Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future, and a novel strategy for healing severe burns.

Dataset Information

Adipose-Derived Regenerative Cell Therapy for Burn Wound Healing: A Comparison of Two Delivery Methods.

Publications

Adipose-Derived Regenerative Cell Therapy for Burn Wound Healing: A Comparison of Two Delivery Methods.

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