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.

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.

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.

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.

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.

Intestinal duplication in the tongue: embryological and radiological point of view.

Intestinal duplication in the tongue is a rare entity. Occurrence in the anterior part of the tongue is exceptional. We report an intestinal duplication in the tongue causing eating difficulties and discuss the accuracy of embryologic and histopathology knowledge as radiology. A transoral complete resection of the lesion was performed, without postoperative complications. There was no recurrence with a follow-up of 15 years.

[New features in the management of labio-maxillo-palatal clefts at the CHUV]. / Nouveautés dans la prise en charge des fentes labio-maxillo-palatines au CHUV.

The labio-maxillofacial cleft (LMFC) penalizes the child from birth by its aesthetic, functional, psychological and social repercussions. The prognosis is conditioned by a multidisciplinary care that starts from the antenatal period to continue until the end of growth. The treatment is long and complex. This explains the multiplicity of techniques and the variability of schedules according to the teams. The purpose of this article is to describe the protocol of management of the LMFC within the multi-disciplinary team in Lausanne and to emphasize the novelties in both surgical and organizational plan.

La fente labio-maxillo-palatine (FLMP) pénalise l'enfant dès sa naissance par ses retentissements esthétiques, fonctionnels, psychologiques et sociaux. Le pronostic est conditionné par une prise en charge multidisciplinaire qui commence dès la période anténatale pour se poursuivre jusqu'à la fin de la croissance. Le traitement est long et complexe. Ceci explique la multiplicité des techniques et la variabilité des calendriers selon les équipes. Le but de cet article est de décrire le protocole de prise en charge des FLMP au sein de l'équipe pluridisciplinaire lausannoise et en mettant l'accent sur les nouveautés tant sur le plan chirurgical qu'organisationnel.

The Mandibular Ramus: An Alternative Donor Site for Secondary Alveolar Bone Grafting in Clefts of the Alveolus.

The authors describe the use of the mandibular ramus as an autologous bone graft material for secondary alveolar bone grafting in cleft patients. This technique represents a safe and effective alternative to currently used donor sites. Furthermore, it allows to minimize patient discomfort, so that they can be treated as outpatients.

L-Shaped Septal Extension Spreader Graft for Improvement of Tip Symmetry in Unilateral Cleft Lip Nose Deformities.

INTRODUCTION: The unilateral cleft lip nose is characterized by numerous complex and interdependent deformities. Secondary rhinoplasty techniques aim to correct cleft lip nose deformities by using multiple maneuvers combining septum and nasal spine medialization and alar cartilage, as well as soft tissue mobilization and repositioning. Moreover, cartilage grafting is frequently used to restore adequate tip projection and nasal symmetry. We present a technique of cartilage grafting commonly used in noncleft rhinoplasties that we modified for cases of moderate cleft lip nose deformities. PATIENTS AND METHODS: We present a retrospective case study of 21 patients with moderate unilateral cleft lip nose deformities who underwent secondary septorhinoplasty with an L-shaped septal extension spreader graft combined with alar rim, alar batten graft, and soft tissue repositioning. Exclusion criteria were severe or complex septal deviation avoiding a stable fixation of the graft. Mean follow-up time was 28 months. Surgical outcomes were analyzed by anthropometric measurements of standardized preoperative and postoperative photographs. RESULTS: All parameters improved except for the nostril height. The height between the alar base and the dome defining dome symmetry, as well as the angles between the lower lateral cartilage and the alar base (α) defining the orientation of the alar rim, improved significantly. The mean ratios of cleft/noncleft side of the height between the alar base and the dome and α showed statistically significant improvements from 0.833 (preoperative) to 0.994 (postoperative) (P < 0.0001) and from 0.883 to 1.02 (P = 0.0038), respectively. CONCLUSIONS: The L-shaped septal extension spreader graft combined with alar batten graft and soft tissue repositioning is an option for secondary rhinoplasties in unilateral cleft lip nose deformities minimizing tip rigidity with significant improvement of the dome's height and its symmetry, as well as the alar side angle.

[Velopharyngeal insufficiency in children]. / Insuffisance vélo-pharyngée chez l'enfant.

Velopharyngeal insufficiency (VPI) represents an incomplete closure between the soft palate and the posterior pharyngeal wall. Its etiology can be anatomical (cleft palate), neurologic, or iatrogenic (after adenoidectomy). The evaluation of a VPI begins with a through speech and language assessment and can be complemented by instrumental investigations. VPI treatment relies on its early identification, followed by a specific speech therapy management. Surgery is performed in case of no improvement with speech therapy or in case of an anatomical defect not allowing the child to improve. IVP management requires a multidisciplinary team.

L'insuffisance vélo-pharyngée (IVP) désigne un défaut d'occlusion entre le voile du palais et la paroi postérieure du pharynx. Son étiologie peut être d'ordres anatomique (fente palatine), neurologique ou iatrogène (adénoïdectomie). L'évaluation de l'IVP débute par un bilan phoniatrique et orthophonique détaillé et peut être complétée par des explorations instrumentales. Son traitement repose sur une identification précoce puis une prise en charge et un suivi orthophonique spécifiques. Une chirurgie est réalisée en cas d'absence d'amélioration ou de défaut anatomique ne permettant pas à l'enfant de progresser. L'IVP est une pathologie intéressant plus particulièrement l'enfant et sa prise en charge se fait par une équipe multidisciplinaire.

Rhinopharyngeal autologous fat injection for treatment of velopharyngeal insufficiency in patients with cleft palate.

Patients with cleft palate are prone to velopharyngeal insufficiency. In minor cases or when hypernasal speech does not resolve after velopharyngoplasty, an augmentation pharyngoplasty with autologous fat can be proposed. The aim of the present study is to evaluate the short-term (within 2 months) and long-term efficiency (during the 24 months following the procedure) of our procedure in the setting of velopharyngeal insufficiency related to a cleft palate. Twenty-two patients with cleft palate related velopharyngeal insufficiency were included in this retrospective study. All patients were operated following the same technique, in the same institution. The pre- and postoperative evaluations included a nasometry, a subjective evaluation using the Borel-Maisonny score, and a nasofibroscopy to assess the degree of velopharyngeal closure. Scores of Borel-Maisonny and nasometry were compared before, shortly after the procedure (within 2 months) and long term after the procedure (within 24 months). Forty-one procedures in 22 patients with a cleft palate performed in our institution between October 2004 and January 2012 were included in the study. Nine patients had a previous velopharyngoplasty with persistent rhinolalia despite intensive speech therapy. In 14 patients the procedure was repeated because of recurrent hypernasal speech after the first injection. The average number of procedures per patient was 1.8. Postoperative nasometry and Borel-Maisonny scores were statistically significantly improved and remained stable until the end of the follow-up (median 42 months postoperative) in most patients. Complications were rare and minor. Autologous fat injection is a simple procedure for treatment of minor velopharyngeal insufficiencies in patients with cleft palate, with good long-term results and few complications.

Outcomes of Colonic and Gastric Tube Transplants after Caustic Esophageal Burn in Children: A 33-Year Review.

Introduction: Accidental caustic burns of the esophagus in children represent a significant global health challenge, often necessitating esophageal reconstruction. The aim of this study is to compare the efficacy and morbidity related to esophagus replacement with colonic and gastric tube transplants in a pediatric population followed for caustic stenosis. Methods: This retrospective study was conducted at a tertiary pediatric surgery unit for children treated from January 1989 to December 2022. We compared colonic and gastric tube esophageal replacement. Short term (within 30 days) and mid-term outcomes and complications were reviewed. Statistical evaluation was considered using a Chi-square test for categorical data analysis. Results: A total of 124 children with caustic esophageal burns were included. Among them, 23 (18.5%) had a gastric tube transplant for esophagus replacement and 101 (81.5%) a colonic transplant. During surgical intervention, we found a significantly higher risk of complications when using a colonic transplant (34%, p < 0.001). There was no significant statistical difference in postoperative short term and mid-term complications between the two techniques. Twenty-six (26%) of the children required a reoperation, with a higher risk in the gastric tube transplant group (p < 0.001). Endoscopic dilatation after surgery was also performed on a higher number of children who had received a gastric tube transplant (p = 0.005). Overall, 97.6% recovered full normal oral feeding. Conclusions: We found that colonic and gastric tube replacement are both good options for pediatric esophageal replacement after a caustic injury and show effectiveness over time. Gastric tube transplants carried a slightly higher risk of reoperations and a higher number of dilatations post-surgery. However, our groups are not really comparable, due to the much higher number of colonic transplants. Both surgical options have to be considered during surgery, and the choice depends on the anatomy of the patient. Our future research will focus on assessing long term quality of life and the potential risk of neoplastic complications.

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.

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.

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.

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.

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.

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.

Success and failure for children born with facial clefts in Africa: a 15-year follow-up.

BACKGROUND: This study reviews the 15 year program of our Department of Pediatric Surgery for the treatment and follow-up of children born with a cleft in Benin and Togo. METHODS: We analyzed files of children born in Africa with a cleft. They were referred to us through a nongovernmental organization (NGO) between 1993 and 2008 and assessed in Africa by local pediatricians before and after surgery. Operations were performed by our team. RESULTS: Two hundred files were reviewed: 60 cases of unilateral cleft lip, seven of bilateral cleft lip, 44 of unilateral cleft lip palate (UCLP), 29 of bilateral cleft lip palate (BCLP), 53 of cleft palate (CP), three of bilateral oro-ocular cleft, one of unilateral and two of median clefts (Binder), and one of commissural cleft. Sixty-nine (35 %) of these cases were not operated in Africa: 25 (12.5 %) had not shown up, 28 (15 %) were considered unfit for surgery (Down's syndrome, HIV-positive, malnutrition, cardiac malformation), and 16 (7.5 %) were transferred to Switzerland. Palatal fistula occurred in 20 % of UCLP, 30 % of BCLP, and 16 % of CP. Evaluation of speech after palate surgery gave less than 50 % of socially acceptable speech. CONCLUSIONS: Our partnership with a NGO and a local team makes it possible to treat and subsequently follow children born with a cleft in West Africa. Surgery is performed under good conditions. If aesthetic results are a success, functional results after palate surgery need further improvement to promote integration in school and social life.

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.