MSCs seeded on bioengineered scaffolds improve skin wound healing in rats

Abstract

Growing evidence has shown the promise of mesenchymal stromal cells (MSCs) for the treatment of cutaneous wound healing. We have previously demonstrated that MSCs seeded on an artificial dermal matrix, Integra (Integra Lifesciences Corp., Plainsboro, NJ) enriched with platelet-rich plasma (Ematrix) have enhanced proliferative potential in vitro as compared with those cultured on the scaffold alone. In this study, we extended the experimentation by evaluating the efficacy of the MSCs seeded scaffolds in the healing of skin wounds in an animal model in vivo. It was found that the presence of MSCs within the scaffolds greatly ameliorated the quality of regenerated skin, reduced collagen deposition, enhanced reepithelization, increased neo-angiogenesis, and promoted a greater return of hair follicles and sebaceous glands. The mechanisms involved in these beneficial effects were likely related to the ability of MSCs to release paracrine factors modulating the wound healing response. MSC-seeded scaffolds, in fact, up-regulated matrix metalloproteinase 9 expression in the extracellular matrix and enhanced the recruitment of endogenous progenitors during tissue repair. In conclusion, the results of this study provide evidence that the treatment with MSC-seeded scaffolds of cutaneous wounds contributes to the recreation of a suitable microenvironment for promoting tissue repair/regeneration at the implantation sites.Bone marrow-derived mesenchymal stromal cells (MSCs) generate great expectation in the field of regenerative medicine due to the easy isolation and expansion, unique antiinflammatory and immune-modulatory properties, and their potential multipotency.

Adipose Tissue-Derived Microvascular Fragments Improve Vascularization, Lymphangiogenesis, and Integration of Dermal Skin Substitutes

“…However, the vascularization process may still be too slow, because it is subject to the physiological kinetics of angiogenesis with an average vessel growth rate of only 5 mm/h (Utzinger et al, 2015). In contrast, prevascularization approaches aim at the establishment of preformed microvascular networks within scaffolds before their implantation (Athanassopoulos et al, 2012;Egañ a et al, 2009;Formigli et al, 2015;Meruane et al, 2012). These networks are then rapidly perfused by developing interconnections to the microvessels at the implantation site by inosculation (Laschke et al, 2009).…”

Function and Therapeutic Potential of Mesenchymal Stem Cells and Their Acellular Derivatives on Non-Healing Chronic Skin Ulcers

“…Similarly, available artificial dermal matrices, such as Integra ® , have been modified to behave as an ECM for MSC culture. Formigli et al seeded BM-MSCs on Integra ® matrices pre-coated with platelet-rich plasma in order to optimize MSC engraftment on the wound area and elucidate the mechanism of MSC action in a full thickness model using rats [56]. The authors demonstrated that the MSC-seeded Integra ® matrix accelerated healing, promoted complete re-epithelization, induced hair follicle appearance, and enhanced blood vessel formation.…”

“…Rustad et al assessed the in vivo differentiation of engrafted BM-MSCs after 14 days of wound healing in mice, and showed their capacity to differentiate into pericytes and ECs but not into keratinocytes [45]. Similarly, Formigli et al showed that BM-MSCs did not transdifferentiate into keratinocytes, but instead promoted the differentiation of neighboring cells [56]. That said, the transdifferentiation process may depend on the wound microenvironment as well as the delivery system used to administer the MSCs, which might indicate their potential role in the wound healing process.…”

“…Despite the fact that MSC differentiation and transdifferentiation might play a critical role in wound healing, a number of studies have revealed poor MSC engraftment when they are injected in the wounds [56,121]. In this context, Wu et al demonstrated by means of a tracing assay that injected BM-MSCs disappeared in the first 24 hours after delivery into dermal fibrotic skin regions in mice.…”

Trauma and Stem Cells: Biology and Potential Therapeutic Implications

“…This was used in diabetic rats and resulted in improved healing through enhanced neovascularization, granulation and re-epithelialisation. Similarly, Formigli et al [98] used bovine tendon as a scaffold for MSC in treatment of skin defects in rats and observed enhanced healing.…”