Autologous Cultured Fibroblasts As Cellular Therapy In Plastic Surgery

Boss, William K.; Usal, Hakan; Chernoff, Gregory; Keller, Gregory S.; Lask, Gary; Fodor, Peter B.

doi:10.1016/s0094-1298(20)32764-4

Cited by 54 publications

(17 citation statements)

References 12 publications

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“…The use of autologous fibroblasts for dermal defect augmentation represents a potentially exciting natural alternative to the use of other filler materials, which meets all the above-mentioned requirements. Although phase III clinical trials and histological analysis have demonstrated sustained clinical improvement by increased collagen formation and dermal thickness (2,3,8,17,18), proper preclinical investigations are necessary to identify the growth character and to ensure biological safety and functional activity of fibroblasts both before and after transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical use of injectable autologous skin-derived fibroblasts was first started by Isolagen Technologies in 1995 to repair dermal and subcutaneous contour deformity. Longterm correction and the absence of allergic adverse effects have been reported (1,2,12,17), which made autologous fibroblasts a promising alternative to the use of processed bovine collagen and other foreign materials. A prospective, placebo-controlled, phase III clinical trial has also shown that autologous fibroblast injections can safely and effectively produce improvements in rhytides, acne scars, and other dermal defects that continue for at least 12 months after injection (18).…”

Section: Introductionmentioning

confidence: 99%

“…In this study, our concern is to provide evidence of the preclinical safety of using human skin-derived fibroblasts and to demonstrate their proliferation and secretion activity. Both in vitro and in vivo studies were performed with the following objectives: (1) to prove the genomic stability of in vitro cultured human skin-derived fibroblasts by cell cycle analysis and karyotype analysis; (2) to conform that the proliferation and secretion of the cells are regulated after transplantation by in vitro cocultured with skin extract D and in vivo observation; and (3) to observe in vivo growth characteristics and collagen secretion activity of the cultured human skin fibroblasts after transplanted into nude mouse.…”

Section: Introductionmentioning

confidence: 99%

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Preclinical Safety Studies on Autologous Cultured Human Skin Fibroblast Transplantation

et al. 2014

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Recently, FDA approved the clinical use of autologous fibroblasts (LAVIV TM ) for the improvement of nasolabial fold wrinkles in adults. The use of autologous fibroblasts for the augmentation of dermal and subcutaneous defects represents a potentially exciting natural alternative to the use of other filler materials for its long-term corrective ability and absence of allergic adverse effects proved by clinical application. However, compared to the clinical evidence, preclinical studies are far from enough. In this study, human skin-derived fibroblasts were cultured and expanded for both in vitro and in vivo observations. In vitro, the subcultured fibroblasts were divided into two groups. One set of cells underwent cell cycle and karyotype analysis at passages 5 and 10. The second group of cells was cocultured in medium with different concentrations of human skin extract D for the measurement of collagen concentration and cell count. In vivo, the subcultured fibroblasts were injected into nude mice subcutaneously. Biopsies were taken for morphology observation and specific collagen staining at 1, 2, and 3 months after injection. The results in vitro showed no significant differences in cell cycle distribution between passages 5 and 10. Cell proliferation and secretion were inhibited as the concentration of extract D increased. In vivo, the fibroblasts were remarkably denser on the experimental side with no dysplastic cells. Mitotic cells were easily observed at the end of the first month but were rare at the end of the third month. Type III collagen was detected at the end of the first month, while collagen type I was positive at the end of the second month. The content of both collagens increased as time passed. The above results indicated that the use of the autologous fibroblasts was safe, providing a basic support for clinical use of fibroblasts.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preclinical Safety Studies on Autologous Cultured Human Skin Fibroblast Transplantation

et al. 2014

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“…Fibroblasts are the main functional cells in the dermis, and injection of autologous fibroblasts is regarded to be more beneficial and more persistent than other therapies, such as the various dermal fillers. This type of therapy has been effectively used for dermal and subcutaneous deficiencies since 1995 18 , 35 , and clinical research into for autologous fibroblast therapy has been undertaken since 2001. Research has also shown this approach to be safe and well tolerated 36 .…”

Section: Discussionmentioning

confidence: 99%

“…Because fibroblasts make up the main functional population of cells in the dermis, tissue engineering technology using autologous cultured fibroblasts has been developed, as more beneficial in facial rejuvenation than other therapies 10 , 17 . The method with autologous cultured fibroblasts has been used effectively for dermal and subcutaneous deficiencies since 1995 10 , 18 , 19 . The ideal filler material would be nonallergenic, noncarcinogenic, and nonteratogenic 14 .…”

Section: Introductionmentioning

confidence: 99%

Global Gene Expression of Cultured Human Dermal Fibroblasts: Focus on Cell Cycle and Proliferation Status in Improving the Condition of Face Skin

et al. 2021

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Chronological skin ageing is an inevitable physiological process that results in thin and sagging skin, fine wrinkles, and gradual dermal atrophy. The main therapeutic approaches to soft tissue augmentation involve using dermal fillers, where natural fillers, such as autologous fibroblasts, are involved in generating dermal matrix proteins. The aim of this study was to determine the global transcriptome profile of three passages of dermal autologous fibroblasts from a male volunteer, focusing on the processes of the cell cycle and cell proliferation status to estimate the optimal passage of the tested cells with respect to their reimplantation. We performed K-means clustering and validation of the expression of the selected mRNA by qRT-PCR. Ten genes were selected (ANLN, BUB1, CDC20, CCNA2, DLGAP5, MKI67, PLK1, PRC1, SPAG5, and TPX2) from the top five processes annotated to cluster 5. Detailed microarray analysis of the fibroblast genes indicated that the cell population of the third passage exhibited the highest number of upregulated genes involved in the cell cycle and cell proliferation. In all cases, the results of qRT-PCR confirmed the differences in expression of the selected mRNAs between fibroblasts from the primary culture (C0) and from the first (C1), second (C2), and third (C3) cell passage. Our results thus suggest that these cells might be useful for increasing fibroblast numbers after reimplantation into a recipient's skin, and the method used in this study seems to be an excellent tool for autologous transplantation allowing the rejuvenation of aging skin.

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Assessment of Long-term Outcomes of Soft-Tissue Augmentation by Injecting Fibroblasts Suspended in Hyaluronic Acid Filler

Moon

Kim

Han

et al. 2019

JAMA Facial Plast Surg

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In previous studies, this group has reported that cultured human fibroblasts suspended in hyaluronic acid (HA) filler might have potential use as a long-lasting injectable soft-tissue filler. However, the data were insufficient to determine the long-term outcomes.OBJECTIVE To evaluate the long-term outcomes of cultured human fibroblasts suspended in HA filler used for soft-tissue augmentation. DESIGN, SETTING, AND PARTICIPANTSA long-term case series study was performed. Between January 2010 and December 2013, a total of 38 patients were treated with fibroblast-HA filler mixture to augment nasal dorsa, nasolabial folds, and cheek depressions. Of these 38 patients, patients with follow-up period of greater than 3 years were included in this study. A total of 22 patients met the inclusion criteria.MAIN OUTCOMES AND MEASURES Subjective assessment was performed to evaluate degree and time of resorption, improvement, satisfaction, softness of injection sites, and willingness to recommend this treatment to others. Objective assessment was carried out with patients' photographs. Safety and tolerability were also evaluated for this treatment. RESULTSOf the 22 patients included in this study, 19 were women; mean (SD) patient age was 43 (15) years. All 22 patients experienced improvement following the treatment. Twenty (91%) patients were satisfied with the treatment. Nineteen patients (86%) considered that the injection site was as soft as it was before treatment. Patients' mean (SD) grading of improvement, satisfaction, and softness were 4.50 (0.51) (95% CI, 4.27-4.73), 4.14 (0.71) (95% CI, 3.82-4.45), and 4.82 (0.50) (95% CI, 4.59-5.00) at the last visit, respectively. Objective assessment demonstrated postoperative improvement in all patients: a rating of "much improved" was given to 7 patients (32%) by investigator 1; 8 patients (36%) by investigator 2; and 12 patients (55%) the injecting physician. This treatment was well tolerated; no adverse event was recorded for any patient.CONCLUSIONS AND RELEVANCE Injection of cultured human fibroblasts suspended in HA filler might be successful for long-term soft-tissue augmentation. To our knowledge, this study represents the longest follow-up study of soft-tissue augmentation with a fibroblast-HA filler mixture to date.LEVEL OF EVIDENCE 4.

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Autologous Cultured Fibroblasts As Cellular Therapy In Plastic Surgery

Cited by 54 publications

References 12 publications

Preclinical Safety Studies on Autologous Cultured Human Skin Fibroblast Transplantation

Preclinical Safety Studies on Autologous Cultured Human Skin Fibroblast Transplantation

Global Gene Expression of Cultured Human Dermal Fibroblasts: Focus on Cell Cycle and Proliferation Status in Improving the Condition of Face Skin

Assessment of Long-term Outcomes of Soft-Tissue Augmentation by Injecting Fibroblasts Suspended in Hyaluronic Acid Filler

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