Long-Term Follow-up of Autologous Fibroblast Transplantation for Facial Contour Deformities, A Non-Randomized Phase IIa Clinical Trial.

OBJECTIVE: Recently, the promising potential of fibroblast transplantation has become a novel modality for skin rejuvenation. We investigated the long-term safety and efficacy of autologous fibroblast transplantation for participants with mild to severe facial contour deformities. MATERIALS AND METHODS: In this open-label, single-arm phase IIa clinical trial, a total of 57 participants with wrinkles (n=37, 132 treatment sites) or acne scars (n=20, 36 treatment sites) who had an evaluator's assessment score of at least 2 out 7 (based on a standard photo-guide scoring) received 3 injections of autologous cultured fibroblasts administered at 4-6 week intervals. Efficacy evaluations were performed at 2, 6, 12, and 24 months after the final injection based on evaluator and patient's assessment scores. RESULTS: Our study showed a mean improvement of 2 scores in the wrinkle and acne scar treatment sites. At sixth months after transplantation, 90.1% of the wrinkle sites and 86.1% of the acne scar sites showed at least a one grade improvement on evaluator assessments. We also observed at least a 2-grade improvement in 56.1% of the wrinkle sites and 63.9% of the acne scar sites. A total of 70.5% of wrinkle sites and 72.2% of acne scar sites were scored as good or excellent on patient assessments. The efficacy outcomes remained stable up to 24-month. We did not observe any serious adverse events during the study. CONCLUSION: These results have shown that autologous fibroblast transplantation could be a promising remodeling modality with long-term corrective ability and minimal adverse events (Registration Number: NCT01115634).

A randomized, double-blind, phase I clinical trial of fetal cell-based skin substitutes on healing of donor sites in burn patients.

BACKGROUND: Due to limited graft donor sites in extensive burns, re-harvesting of a single donor area is very common. Given the importance of fetal fibroblasts in accelerating fetal wound healing, fetal cell-based skin substitutes have emerged as a novel therapeutic modality for regenerating damaged skin. In this trial, we aimed to evaluate the safety, feasibility and potential efficacy of application of amniotic membranes seeded with fetal fibroblasts for accelerating donor sites healing in burn patients. METHODS: In this randomized, double-blind, phase I clinical trial, 10 patients with total burn surface area of 10-55% were enrolled. Three equal parts (10×10cm) were selected in donor site of each patient and covered by Vaseline gauze (control group), amniotic membrane (AM group), or amniotic membrane seeded with fetal fibroblasts (AM-F group). Adverse events, pain intensity scores, and wound sizes were recorded on days 4, 8, 11, 14, and 20 post-treatment. Also, histological assessments were done on days 0 and 14 after the surgery. RESULTS: All patients underwent surgery, and no adverse events occurred during the procedure and follow-up period. Significantly lower pain intensity and higher healing rates were observed in AM-F and AM groups compared to the control group. Moreover, mean complete re-epithelializatin in AM-F and AM groups were 10.1±2.4 and 11.3±2.9 days, showing that the healing process was significantly accelerated compared to the control group with mean closure time of 14.8±1.6 days. Histological assessment showed lower inflammatory cells infiltration in AM-F and AM groups compared to control group. CONCLUSIONS: This study indicated the safety of transplantation of amniotic membrane seeded with fetal fibroblasts for treatment of donor sites in burn patients; however, preliminary assessments showed no benefits for this therapeutic modality over amniotic membrane alone. Thus, to draw accurate conclusions, further trials in larger populations should be conducted. LEVEL OF EVIDENCE: This study is assigned as level I.

A single-arm open-label clinical trial of autologous epidermal cell transplantation for stable vitiligo: A 30-month follow-up.

BACKGROUND: Recently, we introduced intralesional injection of autologous epidermal cells as a safe and feasible approach for transplantation in patients with stable vitiligo. This approach resulted in less pain during and after the procedure, no scarring or cobblestone formation at the recipient site, and was more feasible to perform on curved surfaces such as joints, lips, eyelids, ears, and face. OBJECTIVE: In this study, we aimed to investigate the long-term efficacy and safety of this transplantation technique. METHODS: In this open-label and single-arm clinical trial, we enrolled 300 patients with stable vitiligo. We obtained a partial thickness normo-pigmented skin specimen from the patients' thigh-buttock junction with an area of one tenth to one third of the recipient site area. The epidermal cell suspension was prepared by processing the autologous skin specimen. We injected the cell suspension into 1060 vitiligo patches in 300 patients. Patients did not use any adjuvant phototherapy during the study. An experienced dermatologist and patients respectively defined the repigmentation score and self-assessment score at regular follow-up visits for up to 30 months after treatment. The scores represented the repigmentation percentage as follows: 0 (0), I (1%-24%), II (25%-49%), III (50%-74%), and IV (75%-100%). RESULTS: The mean repigmentation score at 3 months post-transplantation was 1.12±0.73. A significant upward trend existed in the mean repigmentation score until 9 months after cell transplantation, when the mean repigmentation score reached to 1.98±1.20. At 9 months after treatment, repigmentation of >50% was obtained in 32.2% of treated patches. Acquired repigmentation remained stable in 79.3% of treated patches during the follow-up period. The number of received cells per cm2 positively influenced the repigmentation score. Patches located on face, neck and trunk showed significantly higher response to the treatment. CONCLUSION: The results of our study demonstrated efficacy and safety of autologus epidermal cell transplantation on repigmentation of vitiligo patches. The achieved repigmentation was stable in the majority of treated patches during the follow-up period.

Treatment of Hypertrophic Scar in Human with Autologous Transplantation of Cultured Keratinocytes and Fibroblasts along with Fibrin Glue.

OBJECTIVE: Hypertrophic scar involves excessive amounts of collagen in dermal layer and may be painful. Nowadays, we can't be sure about effectiveness of procedure for hypertrophic scar management. The application of stem cells with natural scaffold has been the best option for treatment of burn wounds and skin defect, in recent decades. Fibrin glue (FG) was among the first of the natural biomaterials applied to enhance skin deformity in burn patients. This study aimed to identify an efficient, minimally invasive and economical transplantation procedure using novel FG from human cord blood for treatment of hypertrophic scar and regulation collagen synthesis. MATERIALS AND METHODS: In this case series study, eight patients were selected with hypertrophic scar due to full-thickness burns. Human keratinocytes and fibroblasts derived from adult skin donors were isolated and cultured. They were tested for the expression of cytokeratin 14 and vimentin using immunocytochemistry. FG was prepared from pooled cord blood. Hypertrophic scars were extensively excised then grafted by simply placing the sheet of FG containing autologous fibroblast and keratinocytes. Histological analyses were performed using Hematoxylin and eosin (H&E) and Masson's Trichrome (MT) staining of the biopsies after 8 weeks. RESULTS: Cultured keratinocytes showed a high level of cytokeratin 14 expression and also fibroblasts showed a high level of vimentin. Histological analyses of skin biopsies after 8 weeks of transplantation revealed re-epithelialization with reduction of hypertrophic scars in 2 patients. CONCLUSION: These results suggest may be the use of FG from cord blood, which is not more efficient than previous biological transporters and increasing hypertrophic scar relapse, but could lead to decrease pain rate.