Bicomponent Cutaneous Cell Therapy for Early Burn Care: Manufacturing Homogeneity and Epidermis-Structuring Functions of Clinical Grade FE002-SK2 Allogeneic Dermal Progenitor Fibroblasts
<b>Background:</b> The extracellular matrix (ECM), primarily composed of collagen and elastin synthesized by dermal fibroblasts, is critical for mesenchymal tissue integrity. Fibroblast phenotypes vary significantly with the anatomical location and developmental stage. Fetal skin, partic...
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2025-05-01
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| author | Xi Chen Nathalie Hirt-Burri Corinne Scaletta Alexis E. Laurent Lee Ann Applegate |
| author_facet | Xi Chen Nathalie Hirt-Burri Corinne Scaletta Alexis E. Laurent Lee Ann Applegate |
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| description | <b>Background:</b> The extracellular matrix (ECM), primarily composed of collagen and elastin synthesized by dermal fibroblasts, is critical for mesenchymal tissue integrity. Fibroblast phenotypes vary significantly with the anatomical location and developmental stage. Fetal skin, particularly prior to 14 weeks of gestation, exhibits a simplified structure compared to adult skin, characterized by a thin, loose dermal matrix and a single-layered epithelium. <b>Objectives:</b> This study aimed to characterize and functionally compare homogenous progenitor fetal fibroblast (PFF) populations derived from 14-week-old fetal skin with fibroblasts isolated from adult burn patients. <b>Methods:</b> We evaluated the proliferative capacity, collagen synthesis, and differentiation potential (adipogenesis and osteogenesis) of PFF and adult burn patient fibroblasts. Furthermore, we assessed their ability to support skin regeneration using a de-epidermized dermis (DED) model seeded with both PFF and patient-derived keratinocytes. The stability of PFF characteristics was monitored across multiple passages (P5–P12). <b>Results:</b> PFF demonstrated a 2–4-fold increase in proliferation rate and a 30–50% enhancement in collagen production in vitro compared to adult fibroblasts. Notably, PFF exhibited a consistent lack of adipogenic and osteogenic differentiation, an attribute distinct from adult fibroblasts. In the DED model, PFF, even at a low fibroblast-to-keratinocyte ratio (1:5), effectively facilitated the formation of well-organized skin structures, including rete ridges, surpassing the performance of adult fibroblasts and adipose-derived cells. These properties remained stable over multiple passages. <b>Conclusions:</b> The unique attributes of PFF, likely attributable to the simplified microenvironment (i.e., collagen organization) of developing fetal tissue, positions them as a promising source for cell-based therapies. Their inherent high collagen synthesis capacity is particularly advantageous for wound healing applications. Consequently, PFF represent a consistent and readily available resource for developing “off-the-freezer” cutaneous cell therapies, potentially enabling accelerated and improved treatment of severe burn injuries. |
| format | Article |
| id | doaj-art-e4a2ef58496b4e07ba1dae1641b383e7 |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj-art-e4a2ef58496b4e07ba1dae1641b383e72025-08-20T03:27:41ZengMDPI AGPharmaceutics1999-49232025-05-0117669210.3390/pharmaceutics17060692Bicomponent Cutaneous Cell Therapy for Early Burn Care: Manufacturing Homogeneity and Epidermis-Structuring Functions of Clinical Grade FE002-SK2 Allogeneic Dermal Progenitor FibroblastsXi Chen0Nathalie Hirt-Burri1Corinne Scaletta2Alexis E. Laurent3Lee Ann Applegate4Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, SwitzerlandRegenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, SwitzerlandRegenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, SwitzerlandRegenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, SwitzerlandRegenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland<b>Background:</b> The extracellular matrix (ECM), primarily composed of collagen and elastin synthesized by dermal fibroblasts, is critical for mesenchymal tissue integrity. Fibroblast phenotypes vary significantly with the anatomical location and developmental stage. Fetal skin, particularly prior to 14 weeks of gestation, exhibits a simplified structure compared to adult skin, characterized by a thin, loose dermal matrix and a single-layered epithelium. <b>Objectives:</b> This study aimed to characterize and functionally compare homogenous progenitor fetal fibroblast (PFF) populations derived from 14-week-old fetal skin with fibroblasts isolated from adult burn patients. <b>Methods:</b> We evaluated the proliferative capacity, collagen synthesis, and differentiation potential (adipogenesis and osteogenesis) of PFF and adult burn patient fibroblasts. Furthermore, we assessed their ability to support skin regeneration using a de-epidermized dermis (DED) model seeded with both PFF and patient-derived keratinocytes. The stability of PFF characteristics was monitored across multiple passages (P5–P12). <b>Results:</b> PFF demonstrated a 2–4-fold increase in proliferation rate and a 30–50% enhancement in collagen production in vitro compared to adult fibroblasts. Notably, PFF exhibited a consistent lack of adipogenic and osteogenic differentiation, an attribute distinct from adult fibroblasts. In the DED model, PFF, even at a low fibroblast-to-keratinocyte ratio (1:5), effectively facilitated the formation of well-organized skin structures, including rete ridges, surpassing the performance of adult fibroblasts and adipose-derived cells. These properties remained stable over multiple passages. <b>Conclusions:</b> The unique attributes of PFF, likely attributable to the simplified microenvironment (i.e., collagen organization) of developing fetal tissue, positions them as a promising source for cell-based therapies. Their inherent high collagen synthesis capacity is particularly advantageous for wound healing applications. Consequently, PFF represent a consistent and readily available resource for developing “off-the-freezer” cutaneous cell therapies, potentially enabling accelerated and improved treatment of severe burn injuries.https://www.mdpi.com/1999-4923/17/6/692burnscell bankingcell therapychronic woundsextracellular matrixfetal skin |
| spellingShingle | Xi Chen Nathalie Hirt-Burri Corinne Scaletta Alexis E. Laurent Lee Ann Applegate Bicomponent Cutaneous Cell Therapy for Early Burn Care: Manufacturing Homogeneity and Epidermis-Structuring Functions of Clinical Grade FE002-SK2 Allogeneic Dermal Progenitor Fibroblasts Pharmaceutics burns cell banking cell therapy chronic wounds extracellular matrix fetal skin |
| title | Bicomponent Cutaneous Cell Therapy for Early Burn Care: Manufacturing Homogeneity and Epidermis-Structuring Functions of Clinical Grade FE002-SK2 Allogeneic Dermal Progenitor Fibroblasts |
| title_full | Bicomponent Cutaneous Cell Therapy for Early Burn Care: Manufacturing Homogeneity and Epidermis-Structuring Functions of Clinical Grade FE002-SK2 Allogeneic Dermal Progenitor Fibroblasts |
| title_fullStr | Bicomponent Cutaneous Cell Therapy for Early Burn Care: Manufacturing Homogeneity and Epidermis-Structuring Functions of Clinical Grade FE002-SK2 Allogeneic Dermal Progenitor Fibroblasts |
| title_full_unstemmed | Bicomponent Cutaneous Cell Therapy for Early Burn Care: Manufacturing Homogeneity and Epidermis-Structuring Functions of Clinical Grade FE002-SK2 Allogeneic Dermal Progenitor Fibroblasts |
| title_short | Bicomponent Cutaneous Cell Therapy for Early Burn Care: Manufacturing Homogeneity and Epidermis-Structuring Functions of Clinical Grade FE002-SK2 Allogeneic Dermal Progenitor Fibroblasts |
| title_sort | bicomponent cutaneous cell therapy for early burn care manufacturing homogeneity and epidermis structuring functions of clinical grade fe002 sk2 allogeneic dermal progenitor fibroblasts |
| topic | burns cell banking cell therapy chronic wounds extracellular matrix fetal skin |
| url | https://www.mdpi.com/1999-4923/17/6/692 |
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