What We Learned from Performing the Inverse Malek Procedure to Repair Bilateral Cleft Lips and Palates: A Single-Center Retrospective Study.

Background: This study reviews the surgical and functional outcomes of children diagnosed with a bilateral cleft lip and palate and treated by the same surgical team following specific surgical protocols 18 years after surgery and during the follow-up. Methods: Based on a single-center retrospective design, demographic and surgical data were gathered by the authors from international institutions. Most of the data were quantitative in nature, and descriptive statistical and non-parametric tests were employed for analysis. All children born with a bilateral cleft from 1982 to 2002 were considered. Children affected by a syndrome were excluded. Complications and speech results were the main items measured. Results: Thirty patients were selected; 73.3% were treated using the inverse Malek procedure, and 26.7% underwent a modified two-stage procedure. Seventy percent developed an oronasal fistula. An alveolar bone graft was performed in 83%, and 53.3% underwent Le Fort osteotomy. Thirty-six percent required a pharyngeal flap, with good speech results. The median number of times general anesthesia was used among all the interventions considered was 5.5 (4.25-6). Conclusions: This study presents the long-term results of using the inverse Malek procedure to treat children with a bilateral cleft lip and palate. It is shown that this is related to a high risk of developing a fistula, but has good long-term speech results.

A New Ex Vivo Human Skin Burn Model.

Currently, most burn models for preclinical testing are on animals. For obvious ethical, anatomical, and physiological reasons, these models could be replaced with optimized ex vivo systems. The creation of a burn model on human skin using a pulsed dye laser could represent a relevant model for preclinical research. Six samples of excess human abdominal skin were obtained within one hour after surgery. Burn injuries were induced on small samples of cleaned skin using a pulsed dye laser on skin samples, at varying fluences, pulse numbers and illumination duration. In total, 70 burn injuries were performed on skin ex vivo before being histologically and dermato-pathologically analyzed. Irradiated burned skin samples were classified with a specified code representing burn degrees. Then, a selection of samples was inspected after 14 and 21 days to assess their capacity to heal spontaneously and re-epithelize. We determined the parameters of a pulsed dye laser inducing first, second, and third degree burns on human skin and with fixed parameters, especially superficial and deep second degree burns. After 21 days with the ex vivo model, neo-epidermis was formed. Our results showed that this simple, rapid, user-independent process creates reproducible and uniform burns of different, predictable degrees that are close to clinical reality. Human skin ex vivo models can be an alternative to and complete animal experimentation, particularly for preclinical large screening. This model could be used to foster the testing of new treatments on standardized degrees of burn injuries and thus improve therapeutic strategies.

Assessment of Multiple Dimensions of Psychological Well-Being in Swiss Youth Born with a Unilateral Cleft Lip and Palate.

OBJECTIVE: This study examines the psychological well-being of Swiss youths born with a unilateral cleft lip and palate (UCLP), in a multi-dimensional and clinical perspective. DESIGN: Retrospective cross-sectional study. SETTING: Self-report questionnaires completed by youths born with UCLP, followed at a specialized cleft clinic in Switzerland, and by peers without UCLP, recruited in schools of the Vaud county, Switzerland. PARTICIPANTS: Youths aged 7.5 to 16, born with UCLP (clinical group, n = 41, 29.2% female) or without UCLP (control group, n = 56, 49.0% female). OUTCOME MEASURES: Adverse life events (ALE; Adverse Life Events), behavioral and emotional symptoms (Strengths and Difficulties Questionnaire and Post-Traumatic Checklist Scale), bodily self-esteem (Body Esteem Scale), quality of life (Kidscreen-27), emotion regulation (Cognitive Emotion Regulation Questionnaire), social support (Sarason's Social Support Questionnaire). RESULTS: Most outcomes showed no significant group-difference. Compared to matched peers, youths with UCLP reported lower psychological quality of life and social support satisfaction, along with positive factors of fewer ALE and lower non-adaptive emotion regulation. In youths with UCLP, higher scores for ALE were associated with higher total scores for behavioral and emotional symptoms. Higher scores for bodily self-esteem were associated with higher scores for satisfaction of social support and adaptive emotion regulation. CONCLUSIONS: Youths with UCLP show globally similar psychological well-being as matched peers. We observed some vulnerabilities but also protective factors, which support the need for psychological perspective within multidisciplinary care. The relationships between dimensions suggest specific targets that may have an impact in context of intervention.

Cleft Lip and Palate Antenatal Diagnosis: A Swiss University Center Performance Analysis.

Precision of cleft lip and/or palate antenatal diagnosis plays a significant role in counselling, neonatal care, surgical strategies and psychological support of the family. This study aims to measure the accuracy of antenatal diagnosis in our institution and the detection rate of cleft lip and/or palate on routine morphologic ultrasonography. In this retrospective observational study, we compared antenatal and postnatal diagnosis of 233 patients followed in our unit. We classified our patients according to the Kernahan and Stark's classification system: Group 1: facial cleft including labial and labio-maxillary clefts; Group 2: facial cleft including total, subtotal and submucous palatal clefts; Group 3: labio-maxillary-palatal clefts. Out of 233 patients, 104 were antenatally diagnosed with a facial cleft, i.e., an overall detection rate of 44.6%. The diagnosis was confirmed at birth in 65 of these patients, i.e., an overall accuracy of 62.5%. Of the 67 children (29.2%) in Group 1, the screening detection rate was 58.2% with an antenatal diagnostic accuracy of 48.7%. Of the 97 children (41.6%) in Group 2, the screening detection rate was 2% with an antenatal diagnostic accuracy of 50%. Of the 69 children (29.6%) in Group 3, the screening detection rate was 91.3% with an antenatal diagnostic accuracy of 71.4%. Our study demonstrates a relatively poor diagnostic accuracy in prenatal ultrasound, where the diagnosis was inaccurate in one third to one half of patients. It showed great variability in the screening detection rate depending on the diagnostic group observed, as well as a low rate of detection of palatal clefts.

Bullying in Swiss Youth Born with a Unilateral Cleft lip and Palate by Self- and Parent-Report.

OBJECTIVE: This study aimed to gain a better understanding of bullying as victims and aggressors in youths born with unilateral cleft lip and palate (UCLP). DESIGN: This is an observational study comparing youths with UCLP (ages 8-16) and their parents with a control group (CG) of children in state schools and their parents. PARTICIPANTS: Forty-one youths (43% female; mean age 12.4 ± 2.3 years) and their parents (n = 40) composed the UCLP group and 56 youths (47% female; mean age 12.4 ± 1.2 years) and their parents (n = 33) were in the CG. MAIN OUTCOME MEASURE: The Olweus Bully/Victim questionnaire self- and parent-report was used to assess victims and aggressors involved in bullying behaviors. RESULTS: About 30% of all youths reported being a frequent victim of bullying at least 2-3 times a month and an additional 32.3% were bullied 1-2 times in the last 2-3 months. For the total sample, parents significantly (P < .05) underestimated any bullying, both as a victim (youths 62.5% vs parents 45.7%) and as an aggressor (youths 53.1% vs parents 37.1%). There were no significant group differences in experiencing any bullying between the youths with UCLP (52.5%) and the CG youths (69.6%) or in its perception by their parents (43.2% and 48.5%, respectively). There were no group differences between the combinations of victim and aggressor. CONCLUSIONS: While there were no differences in bullying prevalence in our sample between youths with UCLP and their peers, this study highlights differences in bullying perceptions between parents and their children.

Retrospectives on Three Decades of Safe Clinical Experience with Allogeneic Dermal Progenitor Fibroblasts: High Versatility in Topical Cytotherapeutic Care.

Allogeneic dermal progenitor fibroblasts constitute cytotherapeutic contenders for modern cutaneous regenerative medicine. Based on advancements in the relevant scientific, technical, and regulatory fields, translational developments have slowly yet steadily led to the clinical application of such biologicals and derivatives. To set the appropriate general context, the first aim of this study was to provide a current global overview of approved cell and gene therapy products, with an emphasis on cytotherapies for cutaneous application. Notable advances were shown for North America, Europe, Iran, Japan, and Korea. Then, the second and main aim of this study was to perform a retrospective analysis on the various applications of dermal progenitor fibroblasts and derivatives, as clinically used under the Swiss progenitor cell transplantation program for the past three decades. Therein, the focus was set on the extent and versatility of use of the therapies under consideration, their safety parameters, as well as formulation options for topical application. Quantitative and illustrative data were summarized and reported for over 300 patients treated with various cell-based or cell-derived preparations (e.g., progenitor biological bandages or semi-solid emulsions) in Lausanne since 1992. Overall, this study shows the strong current interest in biological-based approaches to cutaneous regenerative medicine from a global developmental perspective, as well as the consolidated local clinical experience gathered with a specific and safe allogeneic cytotherapeutic approach. Taken together, these current and historical elements may serve as tangible working bases for the further optimization of local and modern translational pathways for the provision of topical cytotherapeutic care.

Lyophilized Progenitor Tenocyte Extracts: Sterilizable Cytotherapeutic Derivatives with Antioxidant Properties and Hyaluronan Hydrogel Functionalization Effects.

Cultured primary progenitor tenocytes in lyophilized form were previously shown to possess intrinsic antioxidant properties and hyaluronan-based hydrogel viscosity-modulating effects in vitro. The aim of this study was to prepare and functionally characterize several stabilized (lyophilized) cell-free progenitor tenocyte extracts for inclusion in cytotherapy-inspired complex injectable preparations. Fractionation and sterilization methods were included in specific biotechnological manufacturing workflows of such extracts. Comparative and functional-oriented characterizations of the various extracts were performed using several orthogonal descriptive, colorimetric, rheological, mechanical, and proteomic readouts. Specifically, an optimal sugar-based (saccharose/dextran) excipient formula was retained to produce sterilizable cytotherapeutic derivatives with appropriate functions. It was shown that extracts containing soluble cell-derived fractions possessed conserved and significant antioxidant properties (TEAC) compared to the freshly harvested cellular starting materials. Progenitor tenocyte extracts submitted to sub-micron filtration (0.22 µm) and 60Co gamma irradiation terminal sterilization (5−50 kGy) were shown to retain significant antioxidant properties and hyaluronan-based hydrogel viscosity modulating effects. Hydrogel combination products displayed important efficacy-related characteristics (friction modulation, tendon bioadhesivity) with significant (p < 0.05) protective effects of the cellular extracts in oxidative environments. Overall, the present study sets forth robust control methodologies (antioxidant assays, H2O2-challenged rheological setups) for stabilized cell-free progenitor tenocyte extracts. Importantly, it was shown that highly sensitive phases of cytotherapeutic derivative manufacturing process development (purification, terminal sterilization) allowed for the conservation of critical biological extract attributes.

Exploring the Place of Fish Skin Grafts with Omega-3 in Pediatric Wound Management.

Wound healing in the pediatric population is known to be a challenge and poorly studied. Split-thickness skin grafts, full-thickness skin grafts, and flaps overlap their applications with the growing field of cellular and tissue-based therapies. However, their role in pediatric reconstruction has yet to be defined. The Kerecis® Omega-3 wound patch, derived from decellularized codfish skin, has garnered attention due to its preserved microscopic architecture resembling the human extracellular matrix. This acellular dermal matrix acts as a scaffold, fostering dermal cell and capillary adhesion while harnessing omega-3 polyunsaturated fatty acids for granulation acceleration and antimicrobial effects. This study presents a comprehensive review and surgical protocol for utilizing Kerecis® fish skin in pediatric wound care. The research embraces a case series involving five patients with diverse wound locations. The Kerecis® Omega-3 wound patch underwent meticulous application and careful monitoring. The results highlight an average time of 48.6 days for complete epithelialization, yielding favorable outcomes with no hypertrophic scarring and mild retraction. Kerecis® fish skin grafting stands as a tool that not only accelerates healing but also addresses the multifaceted challenges associated with wound management in the pediatric population: the avoidance of donor site morbidity and improved postoperative pain control.

Unilateral Cleft lip and Palate: Long-Term Results of the Malek Technique.

To review at 18 years-old the results of surgery and follow-up of children born in our hospital with unilateral cleft lip and palate (uCLP). They were operated at the time by the same surgeon, following the same primary surgical procedure (Malek).Retrospective cohort study.Tertiary Children's Hospital.All children born with uCLP between 1996 and 2001 and operated in our hospital. Syndromic children were excluded.Results of the primary surgery, ear-nose-throat interventions, maxillo-facial surgery and final phonatory results.Seventy-nine files of children born with a cleft were reviewed: 34 were taken into consideration for uCLP: 15 right and 19 left. They were operated in two stages, following the inverse Malek procedure. Sixty per cent had a fistula. Eighty-eight percent had grommets. Ninety-seven percent had an alveolar graft at a median age of nine (5-10) and 22% underwent a Le Fort osteotomy. Seven percent were operated for a pharyngeal flap, 29% for a secondary lip surgery at a mean age of 12.8 and 29% for a late rhinoplasty at a mean age of 14.8 years. A median of 5.7 multidisciplinary consultations was realized with a median number of general anesthesia of 7.1 (4-13).This retrospective study shows that the Malek procedure for children born with uCLP is related to a high risk of fistula but good long-term phonatory results. Twenty percent of children were operated for a Le Fort procedure and one-third for a secondary lip procedure and rhinoplasty.

Lymphatic malformations in children: retrospective review of surgical and interventional management.

PURPOSE: Lymphatic malformations (LMs) are classified as macrocystic, microcystic or mixed. Treatment depends on their characteristics: surgery, sclerotherapy, both combined, systemic treatment or observation. This study aims to analyze the surgical and interventional management of LMs in children over the last two decades in our university hospital. METHODS: Management of children born with LMs between 2000 and 2019 was reviewed. Parameters collected were: malformation characteristics, type of treatment, symptoms, imaging, timing of diagnosis and first treatment, number of interventions, recovery rate, complications and length of stay. RESULTS: Files of 48 children were reviewed: 27 with macrocystic and 21 with microcystic LMs. There was no statistically significant difference in type of treatment except for combined treatment, more performed in microcystic LMs (p = 0.04). Symptoms, imaging, timing of diagnosis and first treatment, number of interventions and complications were not statistically significant. Overall, the number of surgeries was lower than sclerotherapies (p = 0.04). Recovery rate after surgery was higher in macrocystic LMs (p = 0.01). Complications and length of stay were not statistically significant. CONCLUSION: A good rate of recovery was observed when surgery was performed, with no significant increase in complications and length of stay. A prospective study will be determinant to create a decisional algorithm for children with LMs.

Back to the Cradle of Cytotherapy: Integrating a Century of Clinical Research and Biotechnology-Based Manufacturing for Modern Tissue-Specific Cellular Treatments in Switzerland.

Empirically studied by Dr. Brown-Séquard in the late 1800s, cytotherapies were later democratized by Dr. Niehans during the twentieth century in Western Switzerland. Many local cultural landmarks around the Léman Riviera are reminiscent of the inception of such cell-based treatments. Despite the discreet extravagance of the remaining heirs of "living cell therapy" and specific enforcements by Swiss health authorities, current interest in modern and scientifically sound cell-based regenerative medicine has never been stronger. Respective progress made in bioengineering and in biotechnology have enabled the clinical implementation of modern cell-based therapeutic treatments within updated medical and regulatory frameworks. Notably, the Swiss progenitor cell transplantation program has enabled the gathering of two decades of clinical experience in Lausanne for the therapeutic management of cutaneous and musculoskeletal affections, using homologous allogeneic cell-based approaches. While striking conceptual similarities exist between the respective works of the fathers of cytotherapy and of modern highly specialized clinicians, major and important iterative updates have been implemented, centered on product quality and risk-analysis-based patient safety insurance. This perspective article highlights some historical similarities and major evolutive differences, particularly regarding product safety and quality issues, characterizing the use of cell-based therapies in Switzerland over the past century. We outline the vast therapeutic potential to be harnessed for the benefit of overall patient health and the importance of specific scientific methodological aspects.

Combination of Hyaluronan and Lyophilized Progenitor Cell Derivatives: Stabilization of Functional Hydrogel Products for Therapeutic Management of Tendinous Tissue Disorders.

Cultured progenitor cells and derivatives have been used in various homologous applications of cutaneous and musculoskeletal regenerative medicine. Active pharmaceutical ingredients (API) in the form of progenitor cell derivatives such as lysates and lyophilizates were shown to retain function in controlled cellular models of wound repair. On the other hand, hyaluronan-based hydrogels are widely used as functional vehicles in therapeutic products for tendon tissue disorders. The aim of this study was the experimental characterization of formulations containing progenitor tenocyte-derived APIs and hyaluronan, for the assessment of ingredient compatibility and stability in view of eventual therapeutic applications in tendinopathies. Lyophilized APIs were determined to contain relatively low quantities of proteins and growth factors, while being physicochemically stable and possessing significant intrinsic antioxidant properties. Physical and rheological quantifications of the combination formulas were performed after hydrogen peroxide challenge, outlining significantly improved evolutive viscoelasticity values in accelerated degradation settings. Thus, potent effects of physicochemical protection or stability enhancement of hyaluronan by the incorporated APIs were observed. Finally, combination formulas were found to be easily injectable into ex vivo tendon tissues, confirming their compatibility with further translational clinical approaches. Overall, this study provides the technical bases for the development of progenitor tenocyte derivative-based injectable therapeutic products or devices, to potentially be applied in tendinous tissue disorders.

Hypoxic Incubation Conditions for Optimized Manufacture of Tenocyte-Based Active Pharmaceutical Ingredients of Homologous Standardized Transplant Products in Tendon Regenerative Medicine.

Human fetal progenitor tenocytes (hFPT) produced in defined cell bank systems have recently been characterized and qualified as potential therapeutic cell sources in tendon regenerative medicine. In view of further developing the manufacture processes of such cell-based active pharmaceutical ingredients (API), the effects of hypoxic in vitro culture expansion on key cellular characteristics or process parameters were evaluated. To this end, multiple aspects were comparatively assessed in normoxic incubation (i.e., 5% CO2 and 21% O2, standard conditions) or in hypoxic incubation (i.e., 5% CO2 and 2% O2, optimized conditions). Experimentally investigated parameters and endpoints included cellular proliferation, cellular morphology and size distribution, cell surface marker panels, cell susceptibility toward adipogenic and osteogenic induction, while relative protein expression levels were analyzed by quantitative mass spectrometry. The results outlined conserved critical cellular characteristics (i.e., cell surface marker panels, cellular phenotype under chemical induction) and modified key cellular parameters (i.e., cell size distribution, endpoint cell yields, matrix protein contents) potentially procuring tangible benefits for next-generation cell manufacturing workflows. Specific proteomic analyses further shed some light on the cellular effects of hypoxia, potentially orienting further hFPT processing for cell-based, cell-free API manufacture. Overall, this study indicated that hypoxic incubation impacts specific hFPT key properties while preserving critical quality attributes (i.e., as compared to normoxic incubation), enabling efficient manufacture of tenocyte-based APIs for homologous standardized transplant products.

Evolution of Diploid Progenitor Lung Cell Applications: From Optimized Biotechnological Substrates to Potential Active Pharmaceutical Ingredients in Respiratory Tract Regenerative Medicine.

The objective of this review is to describe the evolution of lung tissue-derived diploid progenitor cell applications, ranging from historical biotechnological substrate functions for vaccine production and testing to current investigations around potential therapeutic use in respiratory tract regenerative medicine. Such cell types (e.g., MRC-5 or WI-38 sources) were extensively studied since the 1960s and have been continuously used over five decades as safe and sustainable industrial vaccine substrates. Recent research and development efforts around diploid progenitor lung cells (e.g., FE002-Lu or Walvax-2 sources) consist in qualification for potential use as optimal and renewed vaccine production substrates and, alternatively, for potential therapeutic applications in respiratory tract regenerative medicine. Potentially effective, safe, and sustainable cell therapy approaches for the management of inflammatory lung diseases or affections and related symptoms (e.g., COVID-19 patients and burn patient severe inhalation syndrome) using local homologous allogeneic cell-based or cell-derived product administrations are considered. Overall, lung tissue-derived progenitor cells isolated and produced under good manufacturing practices (GMP) may be used with high versatility. They can either act as key industrial platforms optimally conforming to specific pharmacopoeial requirements or as active pharmaceutical ingredients (API) for potentially effective promotion of lung tissue repair or regeneration.

Burn Center Organization and Cellular Therapy Integration: Managing Risks and Costs.

The complex management of severe burn victims requires an integrative collaboration of multidisciplinary specialists in order to ensure quality and excellence in healthcare. This multidisciplinary care has quickly led to the integration of cell therapies in clinical care of burn patients. Specific advances in cellular therapy together with medical care have allowed for rapid treatment, shorter residence in hospitals and intensive care units, shorter durations of mechanical ventilation, lower complications and surgery interventions, and decreasing mortality rates. However, naturally fluctuating patient admission rates increase pressure toward optimized resource utilization. Besides, European translational developments of cellular therapies currently face potentially jeopardizing challenges on the policy front. The aim of the present work is to provide key considerations in burn care with focus on architectural and organizational aspects of burn centers, management of cellular therapy products, and guidelines in evolving restrictive regulations relative to standardized cell therapies. Thus, based on our experience, we present herein integrated management of risks and costs for preserving and optimizing clinical care and cellular therapies for patients in dire need.

Industrial Development of Standardized Fetal Progenitor Cell Therapy for Tendon Regenerative Medicine: Preliminary Safety in Xenogeneic Transplantation.

Tendon defects require multimodal therapeutic management over extensive periods and incur high collateral burden with frequent functional losses. Specific cell therapies have recently been developed in parallel to surgical techniques for managing acute and degenerative tendon tissue affections, to optimally stimulate resurgence of structure and function. Cultured primary human fetal progenitor tenocytes (hFPT) have been preliminarily considered for allogeneic homologous cell therapies, and have been characterized as stable, consistent, and sustainable cell sources in vitro. Herein, optimized therapeutic cell sourcing from a single organ donation, industrial transposition of multi-tiered progenitor cell banking, and preliminary preclinical safety of an established hFPT cell source (i.e., FE002-Ten cell type) were investigated. Results underlined high robustness of FE002-Ten hFPTs and suitability for sustainable manufacturing upscaling within optimized biobanking workflows. Absence of toxicity or tumorigenicity of hFPTs was demonstrated in ovo and in vitro, respectively. Furthermore, a 6-week pilot good laboratory practice (GLP) safety study using a rabbit patellar tendon partial-thickness defect model preliminarily confirmed preclinical safety of hFPT-based standardized transplants, wherein no immune reactions, product rejection, or tumour formation were observed. Such results strengthen the rationale of the multimodal Swiss fetal progenitor cell transplantation program and prompt further investigation around such cell sources in preclinical and clinical settings for musculoskeletal regenerative medicine.

Frontoethmoidal Encephalocele Correction Surgery in Benin: A Case Report.

INTRODUCTION: Primary encephalocele is a rare deformity that is challenging for the neurosurgeon. It requires a multidisciplinary team for adequate reconstructive surgery. CASE PRESENTATION: We report the case of a 6-month-old African boy who presented with a frontoethmoidal encephalocele; we present a technical description of the surgical procedure, using no implant. DISCUSSION/CONCLUSION: The postoperative evolution of the boy was uneventful, with a good clinical result at the follow-up.

Swiss Fetal Transplantation Program and Non-enzymatically Isolated Primary Progenitor Cell Types for Regenerative Medicine.

Primary progenitor cell types adequately isolated from fetal tissue samples present considerable therapeutic potential for a wide range of applications within allogeneic musculoskeletal regenerative medicine. Progenitor cells are inherently differentiated and extremely stable in standard bioprocessing conditions and can be culture-expanded to establish extensive and robust cryopreserved cell banks. Stringent processing conditions and exhaustive traceability are prerequisites for establishing a cell source admissible for further cGMP biobanking and clinical-grade production lot manufacture. Transplantation programs are ideal platforms for the establishment of primary progenitor cell sources to be used for manufacture of cell therapies or cell-based products. Well-defined and regulated procurement and processing of fetal biopsies after voluntary pregnancy interruptions ensure traceability and safety of progeny materials and therapeutic products derived therefrom. We describe herein the workflows and specifications devised under the Swiss Fetal Progenitor Cell Transplantation Program in order to traceably isolate primary progenitor cell types in vitro and to constitute Parental Cell Banks fit for subsequent industrial-scale cGMP processing. When properly devised, derived, and maintained, such cell sources established after a single organ donation can furnish sufficient progeny materials for years of development in translational musculoskeletal regenerative medicine.

GMP Tiered Cell Banking of Non-enzymatically Isolated Dermal Progenitor Fibroblasts for Allogenic Regenerative Medicine.

Non-enzymatically isolated primary dermal progenitor fibroblasts derived from fetal organ donations are ideal cell types for allogenic musculoskeletal regenerative therapeutic applications. These cell types are differentiated, highly proliferative in standard in vitro culture conditions and extremely stable throughout their defined lifespans. Technical simplicity, robustness of bioprocessing and relatively small therapeutic dose requirements enable pragmatic and efficient production of clinical progenitor fibroblast lots under cGMP standards. Herein we describe optimized and standardized monolayer culture expansion protocols using dermal progenitor fibroblasts isolated under a Fetal Transplantation Program for the establishment of GMP tiered Master, Working and End of Production cryopreserved Cell Banks. Safety, stability and quality parameters are assessed through stringent testing of progeny biological materials, in view of clinical application to human patients suffering from diverse cutaneous chronic and acute affections. These methods and approaches, coupled to adequate cell source optimization, enable the obtention of a virtually limitless source of highly consistent and safe biological therapeutic material to be used for innovative regenerative medicine applications.