Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study

Department of Cardiothoracic Surgery, Great Ormond Street, Hospital for Children, London, UK.
The Lancet (Impact Factor: 45.22). 07/2012; 380(9846):994-1000. DOI: 10.1016/S0140-6736(12)60737-5
Source: PubMed

ABSTRACT Stem-cell-based, tissue engineered transplants might offer new therapeutic options for patients, including children, with failing organs. The reported replacement of an adult airway using stem cells on a biological scaffold with good results at 6 months supports this view. We describe the case of a child who received a stem-cell-based tracheal replacement and report findings after 2 years of follow-up.
A 12-year-old boy was born with long-segment congenital tracheal stenosis and pulmonary sling. His airway had been maintained by metal stents, but, after failure, a cadaveric donor tracheal scaffold was decellularised. After a short course of granulocyte colony stimulating factor, bone marrow mesenchymal stem cells were retrieved preoperatively and seeded onto the scaffold, with patches of autologous epithelium. Topical human recombinant erythropoietin was applied to encourage angiogenesis, and transforming growth factor β to support chondrogenesis. Intravenous human recombinant erythropoietin was continued postoperatively. Outcomes were survival, morbidity, endoscopic appearance, cytology and proteomics of brushings, and peripheral blood counts.
The graft revascularised within 1 week after surgery. A strong neutrophil response was noted locally for the first 8 weeks after surgery, which generated luminal DNA neutrophil extracellular traps. Cytological evidence of restoration of the epithelium was not evident until 1 year. The graft did not have biomechanical strength focally until 18 months, but the patient has not needed any medical intervention since then. 18 months after surgery, he had a normal chest CT scan and ventilation-perfusion scan and had grown 11 cm in height since the operation. At 2 years follow-up, he had a functional airway and had returned to school.
Follow-up of the first paediatric, stem-cell-based, tissue-engineered transplant shows potential for this technology but also highlights the need for further research.
Great Ormond Street Hospital NHS Trust, The Royal Free Hampstead NHS Trust, University College Hospital NHS Foundation Trust, and Region of Tuscany.

Download full-text


Available from: Edward R Samuel, Jan 08, 2015
  • Source
    • "Also, the combined structural integrity of basement membrane components observed, along with retention of angiogenic factors such as bFGF that has been previously reported [8], suggests that neovascularization should be well supported upon transplantation of the graft. Indeed, revascularization of transplanted biotracheas occurs readily over several weeks in humans [27] [17], and the intact basement membrane structures reported in this study will inevitably support vascular responses. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Tissue-engineered airways have achieved clinical success, but concerns remain about short-term loss of biomechanical properties, necessitating a stent. This study investigated the effect of chemical-enzymatic decellularization on biochemical properties of trachea important for cell attachment and vascularization (fibronectin and laminin) and cartilage matrix homeostasis (type II collagen and glycosaminoglycans (GAG)), as well as biomechanical status. Native trachea was used as a control, and NDC trachea stored in phosphate buffered saline (PBS) in parallel to decellularization was used as a time-matched control. Decellularization removed most cells, but chondrocytes and DNA remained after 25 cycles. Fibronectin was retained throughout the lamina propria and laminin at basement membranes. DNA accumulation along ECM fibres was seen. A decline in soluble collagen was observed in decellularized tissue. GAG content of cartilage rings was reduced, even in PBS control tissue from 20 cycles onwards (p<0.05), but decellularization caused the greatest loss (p<0.01). Tensile strength declined throughout the process, but was significant only at later time points. The data demonstrate that the substantial reduction in GAG might contribute to loss of mechanical integrity of biotracheas. Overcoming structural changes that cause an imbalance in cartilage matrix equilibrium will be necessary to optimize clinical benefit, enabling widespread use of biotracheas.
    Acta biomaterialia 10/2012; DOI:10.1016/j.actbio.2012.10.004 · 5.68 Impact Factor
  • Source
    • "No development of anti-donor antibodies or rejection. [59] Cleft lip/palate Dog, BM from iliac bone undifferentiated cell + carrier Carbonated hydroxyapatite particles in vivo MSCs contributed to new bone formation and increase in capillary vessels and particle absorption [60] Craniofacial abnormali- ties human BM osteogeneic cell + scaffold Calcium phosphate cements-chitosan scaffold in vitro MSC had elevated alkaline phosphatase activity and mineralization. Improving the strength of the scaffold [61] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cellular therapy utilizing adult mesenchymal stromal/stem cells (MSCs) may very well revolutionize the treatment of a variety of head and neck diseases through the restoration of normal structure and function. Transplanting allogeneic or autologous MSCs into damaged tissues can serve multiple regenerative functions through their self-renewal, differentiation capacity, immune modulation and secretion of bioactive molecules. Further, trophic factors expressed by MSCs have been shown to influence their microenvironment through the promotion of extracellular matrix remodeling, angiogenesis and wound healing needed to regenerate or replace injured tissues. Although clinical applications of MSC based therapies in Otolaryngology-Head and Neck Surgery are still in their infancy, efforts are being made to understand and exploit MSCs for tissue repair as well as engineering strategies. In this review, we highlight pre clinical and clinical investigations employing MSC based therapies for the reconstruction of bone, cartilage, soft tissue and vocal fold defects.
    01/2012; 1(3):225-38.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Regenerative medicine has developed recently as a new field of science aiming at restoring organ and tissue damage through the use of autologous constructs. Cellular therapies and relatively simple tissue engineering reconstructions have recently been successfully applied into patients. For babies born with congenital diaphragmatic hernia, regenerative medicine may play a role both in developing a myogenic patch capable of restoring muscle function and promoting regeneration of hypoplastic lungs that characterised those patients. The latter is particularly attractive because it may change the long-term outcome of those children. We aim here to discuss recent advancement in the field, looking in particular at the future clinical prospective of those exciting therapeutic strategies.
    European Journal of Pediatric Surgery 10/2012; 22(5):393-8. DOI:10.1055/s-0032-1329410 · 0.98 Impact Factor