Over the past decade different stem cell (SC) based approaches were tested to treat Duchenne Muscular Dystrophy (DMD), a lethal X-linked disorder caused by mutations in dystrophin gene. Despite research efforts, there is no curative therapy for DMD. Allogeneic SC therapies aim to restore dystrophin in the affected muscles; however, they are challenged by rejection and limited engraftment. Thus, there is a need to develop new more efficacious SC therapies. Chimeric Cells (CC), created via ex vivo fusion of donor and recipient cells, represent a promising therapeutic option for tissue regeneration and Vascularized Composite Allotransplantation (VCA) due to tolerogenic properties that eliminate the need for lifelong immunosuppression. This proof of concept study tested feasibility of myoblast fusion for Dystrophin Expressing. Chimeric Cell (DEC) therapy through in vitro characterization and in vivo assessment of engraftment, survival, and efficacy in the mdx mouse model of DMD. Murine DEC were created via ex vivo fusion of normal (snj) and dystrophin–deficient (mdx) myoblasts using polyethylene glycol. Efficacy of myoblast fusion was confirmed by flow cytometry and dystrophin immunostaining, while proliferative and myogenic differentiation capacity of DEC were assessed in vitro. Therapeutic effect after DEC transplant (0.5 × 10⁶) into the gastrocnemius muscle (GM) of mdx mice was assessed by muscle functional tests. At 30 days post-transplant dystrophin expression in GM of injected mdx mice increased to 37.27 ± 12.1% and correlated with improvement of muscle strength and function. Our study confirmed feasibility and efficacy of DEC therapy and represents a novel SC based approach for treatment of muscular dystrophies.

Effective wound management is an important determinant of the survival and prognosis of patients with severe burns. Thus, novel techniques for timely and full closure of full-thickness burn wounds are urgently needed. The purpose of this review is to present the current state of knowledge on the local treatment of burn wounds (distinguishing radiation injury from other types of burns) with the application of cellular therapies conducted in clinical studies. PubMed search engine and ClinicalTrials.gov were used to analyze the available data. The analysis covered 49 articles, assessing the use of keratinocytes (30), keratinocytes and fibroblasts (6), fibroblasts (2), bone marrow-derived cells (8), and adipose tissue cells (3). Studies on the cell-based products that are commercially available (Epicel^®, Keraheal™, ReCell^®, JACE, Biobrane^®) were also included, with the majority of reports found on autologous and allogeneic keratinocytes. Promising data demonstrate the effectiveness of various cell-based therapies; however, there are still scientific and technical issues that need to be solved before cell therapies become standard of care. Further evidence is required to demonstrate the clinical efficacy and safety of cell-based therapies in burns. In particular, comparative studies with long-term follow-up are critical.

Many more patients would benefit from vascularized composite allotransplantation if less toxic and safer immunosuppressive protocols will become available. Tolerance induction protocols with donor cells co-transplantation are one of the promising pathways to reduce maintenance immunosupressive regimens. We investigated the role of donor bone marrow cells (BMC), mesenchymal stromal cells (MSC) and in vivo created chimeric cells (CC) used as supportive therapies in a fully MHC-mismatched rat face transplantation model. Twenty-four fully MHC-mismatched hemiface transplantations were performed between ACI (RT1^a) donors and Lewis (RT1^l) recipients under combined seven-day immunosuppressive regimen of anti-αβ-T-cell receptor (TCR) monoclonal antibody and cyclosporin A. We studied four experimental groups—group 1: no cellular therapy; group 2: supportive therapy with BMC; group 3: supportive therapy with MSC; group 4: supportive therapy with CC generated in a primary chimera. We evaluated clinical and histological rejection grades, transplanted cells migration, donor-specific chimerism in the peripheral blood and bone marrow compartments, and CD4⁺/CD25⁺ T-cell levels. Face allograft rejection was observed at 26.8 ± 0.6 days post-transplant (PT) in the absence of cellular therapy, at 34.5 ± 1.1 days for group 2, 29.3 ± 0.8 days for group 3, and 30.3 ± 1.38 PT for group 4. The longest survival was observed in allografts supported by co-transplantation of BMC. All support in cellular therapies delayed face allograft rejection by chimerism induction and/or immunomodulatory properties of co-transplanted cells. Survival time was comparable between groups, however, further studies, with different cell dosages, delivery routes and delivery times are required.

Purpose of review: Face transplantation represents vascularized composite allotransplantation (VCA) organ and became one of the most rewarding reconstructive options for severely disfigured patients. This review summarizes the past, current and future challenges of face transplantation, based on our experience and literature reports. Recent findings: In 2005, first partial face transplantation was reported by French team. In 2008, we have performed the US first near-total face transplantation. Currently, more than 40 face transplant cases were reported worldwide. Based on the outcomes of our three patients and the literature reports, face transplantation improved aesthetics, function and the quality of life of face transplant patients. However, there are still many challenges encountered including the side effects of immunosuppressive protocols, the psychological and social problems as well as the financial challenges which need to be address in the near future to maintain face transplantation in the armamentarium of reconstructive surgery. Summary: Currently, feasibility of face transplantation was confirmed; however, the life-long immunosuppressive protocols bearing serious side effects are still required to prevent face rejection. Thus, for the future of face and other VCA, novel approaches of cell-based therapies or engineered scaffolds should be developed to make face transplantation safer.