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Therapeutic Strategies for Full‐Thickness Wounds: Skin and Corneal Tissue‐Engineered Substitutes with Stem Cells
Author(s) -
Germain Lucie
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.00371
Subject(s) - dermis , transplantation , basement membrane , stem cell , hemidesmosome , tissue engineering , epidermis (zoology) , ex vivo , regeneration (biology) , microbiology and biotechnology , wound healing , extracellular matrix , chemistry , pathology , anatomy , biomedical engineering , medicine , biology , surgery , in vitro , biochemistry
The LOEX centre of Laval University is specialized in stem cells and tissue engineering. In addition to fundamental research, LOEX focuses on translational medicine to transfer the discoveries into better treatment for the patients. The LOEX self‐assembly approach of tissue engineering was designed to elaborate complex human living tissue substitutes. Autologous self‐assembled skin substitutes (SASSs) are produced to treat wounds of severely burned patients. The procedure is based on primary culturing dermal fibroblasts and keratinocytes from a few cm 2 skin biopsy taken from an unaffected site. Then, dermal fibroblasts are cultured in the presence of ascorbic acid. They secrete and organize their own extracellular matrix (ECM) on which keratinocytes rebuild the epithelium. SASSs exhibit a well‐developed stratified cornified epithelium. The basement membrane is structured and favors long‐term preservation of stem cells in the basal layer of the tissue‐engineered epidermis. The dense collagen network of the tissue‐engineered dermis provides resistance and allow SASS manipulation. After transplantation of autologous SASSs on burn wounds, the graft take was excellent (90–100%). No significant contraction was observed in vivo after grafting. The presence of the ECM promoted a good healing and skin suppleness. SASS presented a well‐organized epidermis and stem cells were settled and maintained in the basal layer after grafting. A complete basement membrane with numerous hemidesmosomes was observed before and after grafting, supporting a strong cohesion between the dermis and epidermis. The integrity of the transplanted SASS persisted over time (1‐ to 8‐year follow‐up) with no defect in epidermal regeneration and no significant contracture. Minimal hypertrophic scars were only observed between SASS. Thus, SASSs provide permanent skin replacement for severe burns. These living substitutes comprising cells and extracellular matrix possess the capability of expanding with the child’s growth. We conclude that the TES produced by this approach is a promising skin substitute for resurfacing full‐thickness skin injury given its functional characteristics: minimal contraction after grafting and promotion of long‐term tissue regeneration. LOEX also used cultured epithelial corneal autografts (CECA), produced from a small biopsy of the limbal area containing stem cells, for the treatment of limbal stem cell deficiency. The first clinical trial is completed, 14 of the 15 patients treated improved their visual conditions. These regenerative medicine technologies pave the way for better treatment of rare diseases. Support or Funding Information Supported by the Canadian Institutes for Health Research (CIHR), The Stem Cell Network, Fonds de Recherche du Québec en Santé (FRQS), Fondation des Pompiers du Québec pour les Grands Brûlés and the Cell and Tissue Therapy Network of the FRQS. LG is holder of the Canada Research Chair on Stem Cells and Tissue Engineering of CIHR.