The objective of this review is to describe the evolution of lung tissue-derived diploid progenit... more 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 pati...
Allogeneic dermal progenitor fibroblasts constitute cytotherapeutic contenders for modern cutaneo... more 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 saf...
Diverse cell therapy approaches constitute prime developmental prospects for managing acute or de... more Diverse cell therapy approaches constitute prime developmental prospects for managing acute or degenerative cartilaginous tissue affections, synergistically complementing specific surgical solutions. Bone marrow stimulation (i.e., microfracture) remains a standard technique for cartilage repair promotion, despite incurring the adverse generation of fibrocartilagenous scar tissue, while matrix-induced autologous chondrocyte implantation (MACI) and alternative autologous cell-based approaches may partly circumvent this effect. Autologous chondrocytes remain standard cell sources, yet arrays of alternative therapeutic biologicals present great potential for regenerative medicine. Cultured human epiphyseal chondro-progenitors (hECP) were proposed as sustainable, safe, and stable candidates for chaperoning cartilage repair or regeneration. This study describes the development and industrial transposition of hECP multi-tiered cell banking following a single organ donation, as well as prel...
Cultured fibroblast progenitor cells (FPC) have been studied in Swiss translational regenerative ... more Cultured fibroblast progenitor cells (FPC) have been studied in Swiss translational regenerative medicine for over two decades, wherein clinical experience was gathered for safely managing burns and refractory cutaneous ulcers. Inherent FPC advantages include high robustness, optimal adaptability to industrial manufacture, and potential for effective repair stimulation of wounded tissues. Major technical bottlenecks in cell therapy development comprise sustainability, stability, and logistics of biological material sources. Herein, we report stringently optimized and up-scaled processing (i.e., cell biobanking and stabilization by lyophilization) of dermal FPCs, with the objective of addressing potential cell source sustainability and stability issues with regard to active substance manufacturing in cutaneous regenerative medicine. Firstly, multi-tiered FPC banking was optimized in terms of overall quality and efficiency by benchmarking key reagents (e.g., medium supplement source, ...
The complex management of severe burn victims requires an integrative collaboration of multidisci... more 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...
Journal of materials science. Materials in medicine, Jan 4, 2018
Emerging 3D printing technology permits innovative approaches to manufacture cartilage scaffolds ... more Emerging 3D printing technology permits innovative approaches to manufacture cartilage scaffolds associated with layer-by-layer mechanical property adaptation. However, information about gradients of mechanical properties in human articular cartilage is limited. In this study, we quantified a zone-dependent change of local elastic modulus of human femoral condyle cartilage by using an instrumented indentation technique. From the cartilage superficial zone towards the calcified layer, a gradient of elastic modulus values between 0.020 ± 0.003 MPa and 6.44 ± 1.02 MPa was measured. To validate the tissue quality, the histological tissue composition was visualized by glycosaminoglycan and collagen staining. This work aims to introduce a new protocol to investigate the zone-dependent mechanical properties of graded structures, such as human articular cartilage. From this knowledge, better cartilage repair strategies could be tailored in the future.
Nosocomial opportunistic fungal infections by Aspergillus spp. represent increasing morbidity and... more Nosocomial opportunistic fungal infections by Aspergillus spp. represent increasing morbidity and mortality factors for severely burned patients, who are fragile and immunocompromised. Voriconazole (VRC), a modern antifungal drug, is used as a first-line therapy against systemic mold and yeast infections. Little has been published about the place, relative importance and efficacy of voriconazole in the treatment protocols involving Aspergillus spp. in Burn Centers. The objective of the present work was to assess the place and importance of voriconazole for the treatment of burn patients presenting superficial Aspergillus spp. infections. We performed a retrospective evaluation of VRC treatment in three severely burned patients with superficial nosocomial Aspergillus spp. infections in our Burn Center. Results showed that VRC allowed for control and cure of topical nosocomial Aspergillus spp. infections. In two cases, treatment with VRC had to be discontinued because of hepatotoxicit...
Cryopreservation and lyophilization processes are widely used for conservation purposes in the ph... more Cryopreservation and lyophilization processes are widely used for conservation purposes in the pharmaceutical, biotechnological, and food industries or in medical transplantation. Such processes deal with extremely low temperatures (e.g., −196 °C) and multiple physical states of water, a universal and essential molecule for many biological lifeforms. This study firstly considers the controlled laboratory/industrial artificial conditions used to favor specific water phase transitions during cellular material cryopreservation and lyophilization under the Swiss progenitor cell transplantation program. Both biotechnological tools are successfully used for the long-term storage of biological samples and products, with reversible quasi-arrest of metabolic activities (e.g., cryogenic storage in liquid nitrogen). Secondly, similarities are outlined between such artificial localized environment modifications and some natural ecological niches known to favor metabolic rate modifications (e.g....
The objective of this review is to describe the evolution of lung tissue-derived diploid progenit... more 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 pati...
Allogeneic dermal progenitor fibroblasts constitute cytotherapeutic contenders for modern cutaneo... more 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 saf...
Diverse cell therapy approaches constitute prime developmental prospects for managing acute or de... more Diverse cell therapy approaches constitute prime developmental prospects for managing acute or degenerative cartilaginous tissue affections, synergistically complementing specific surgical solutions. Bone marrow stimulation (i.e., microfracture) remains a standard technique for cartilage repair promotion, despite incurring the adverse generation of fibrocartilagenous scar tissue, while matrix-induced autologous chondrocyte implantation (MACI) and alternative autologous cell-based approaches may partly circumvent this effect. Autologous chondrocytes remain standard cell sources, yet arrays of alternative therapeutic biologicals present great potential for regenerative medicine. Cultured human epiphyseal chondro-progenitors (hECP) were proposed as sustainable, safe, and stable candidates for chaperoning cartilage repair or regeneration. This study describes the development and industrial transposition of hECP multi-tiered cell banking following a single organ donation, as well as prel...
Cultured fibroblast progenitor cells (FPC) have been studied in Swiss translational regenerative ... more Cultured fibroblast progenitor cells (FPC) have been studied in Swiss translational regenerative medicine for over two decades, wherein clinical experience was gathered for safely managing burns and refractory cutaneous ulcers. Inherent FPC advantages include high robustness, optimal adaptability to industrial manufacture, and potential for effective repair stimulation of wounded tissues. Major technical bottlenecks in cell therapy development comprise sustainability, stability, and logistics of biological material sources. Herein, we report stringently optimized and up-scaled processing (i.e., cell biobanking and stabilization by lyophilization) of dermal FPCs, with the objective of addressing potential cell source sustainability and stability issues with regard to active substance manufacturing in cutaneous regenerative medicine. Firstly, multi-tiered FPC banking was optimized in terms of overall quality and efficiency by benchmarking key reagents (e.g., medium supplement source, ...
The complex management of severe burn victims requires an integrative collaboration of multidisci... more 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...
Journal of materials science. Materials in medicine, Jan 4, 2018
Emerging 3D printing technology permits innovative approaches to manufacture cartilage scaffolds ... more Emerging 3D printing technology permits innovative approaches to manufacture cartilage scaffolds associated with layer-by-layer mechanical property adaptation. However, information about gradients of mechanical properties in human articular cartilage is limited. In this study, we quantified a zone-dependent change of local elastic modulus of human femoral condyle cartilage by using an instrumented indentation technique. From the cartilage superficial zone towards the calcified layer, a gradient of elastic modulus values between 0.020 ± 0.003 MPa and 6.44 ± 1.02 MPa was measured. To validate the tissue quality, the histological tissue composition was visualized by glycosaminoglycan and collagen staining. This work aims to introduce a new protocol to investigate the zone-dependent mechanical properties of graded structures, such as human articular cartilage. From this knowledge, better cartilage repair strategies could be tailored in the future.
Nosocomial opportunistic fungal infections by Aspergillus spp. represent increasing morbidity and... more Nosocomial opportunistic fungal infections by Aspergillus spp. represent increasing morbidity and mortality factors for severely burned patients, who are fragile and immunocompromised. Voriconazole (VRC), a modern antifungal drug, is used as a first-line therapy against systemic mold and yeast infections. Little has been published about the place, relative importance and efficacy of voriconazole in the treatment protocols involving Aspergillus spp. in Burn Centers. The objective of the present work was to assess the place and importance of voriconazole for the treatment of burn patients presenting superficial Aspergillus spp. infections. We performed a retrospective evaluation of VRC treatment in three severely burned patients with superficial nosocomial Aspergillus spp. infections in our Burn Center. Results showed that VRC allowed for control and cure of topical nosocomial Aspergillus spp. infections. In two cases, treatment with VRC had to be discontinued because of hepatotoxicit...
Cryopreservation and lyophilization processes are widely used for conservation purposes in the ph... more Cryopreservation and lyophilization processes are widely used for conservation purposes in the pharmaceutical, biotechnological, and food industries or in medical transplantation. Such processes deal with extremely low temperatures (e.g., −196 °C) and multiple physical states of water, a universal and essential molecule for many biological lifeforms. This study firstly considers the controlled laboratory/industrial artificial conditions used to favor specific water phase transitions during cellular material cryopreservation and lyophilization under the Swiss progenitor cell transplantation program. Both biotechnological tools are successfully used for the long-term storage of biological samples and products, with reversible quasi-arrest of metabolic activities (e.g., cryogenic storage in liquid nitrogen). Secondly, similarities are outlined between such artificial localized environment modifications and some natural ecological niches known to favor metabolic rate modifications (e.g....
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Papers by Lee Applegate