Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Review article: Biomedical intelligence

Vol. 149 No. 1314 (2019)

Tissue engineering for paediatric patients

  • Marcus Mumme
  • Anke Wixmerten
  • Sylvie Miot
  • Andrea Barbero
  • Alexandre Kaempfen
  • Franziska Saxer
  • Sebastian Gehmert
  • Andreas Krieg
  • Dirk J. Schaefer
  • Marcel Jakob
  • Ivan Martin
DOI
https://doi.org/10.4414/smw.2019.20032
Cite this as:
Swiss Med Wkly. 2019;149:w20032
Published
05.04.2019

Summary

The effects of oncological treatment, congenital anomalies, traumatic injuries and post-infection damage critically require sufficient amounts of tissue for structural and functional surgical reconstructions. The patient’s own body is typically the gold standard source of transplant material, but in children autologous tissue is available only in small quantities and with severe morbidity at donor sites. Engineering of tissue grafts starting from a small amount of autologous material, combined with suitable surgical manipulation of the recipient site, is expected to enhance child and adolescent health, and to offer functional restoration for long-term wellbeing. Moreover, engineered tissues based on patient-derived cells represent invaluable models to investigate mechanisms of disease and to develop/test novel therapeutic approaches. In view of these great opportunities, here we introduce the currently limited successful implementation of tissue engineering in paediatric settings and discuss the open challenges in the field. A particular focus is on the specific needs and envisioned strategies in the areas of bone and osteochondral regeneration in children.

References

  1. Langer R, Vacanti JP. Tissue engineering. Science. 1993;260(5110):920–6. doi:.https://doi.org/10.1126/science.8493529
  2. Cancedda R, De Luca M. Tissue engineering for clinical application. Year Immunol. 1993;7:193–8. [Review].
  3. Qu D, Mosher CZ, Boushell MK, Lu HH. Engineering complex orthopaedic tissues via strategic biomimicry. Ann Biomed Eng. 2015;43(3):697–717. doi:.https://doi.org/10.1007/s10439-014-1190-6
  4. Abbas TO, Mahdi E, Hasan A, AlAnsari A, Pennisi CP. Current Status of Tissue Engineering in the Management of Severe Hypospadias. Front Pediatr. 2018;5:283. doi:.https://doi.org/10.3389/fped.2017.00283
  5. Raya-Rivera AM, Esquiliano D, Fierro-Pastrana R, López-Bayghen E, Valencia P, Ordorica-Flores R, et al. Tissue-engineered autologous vaginal organs in patients: a pilot cohort study. Lancet. 2014;384(9940):329–36. doi:.https://doi.org/10.1016/S0140-6736(14)60542-0
  6. Zhou G, Jiang H, Yin Z, Liu Y, Zhang Q, Zhang C, et al. In Vitro Regeneration of Patient-specific Ear-shaped Cartilage and Its First Clinical Application for Auricular Reconstruction. EBioMedicine. 2018;28:287–302. doi:.https://doi.org/10.1016/j.ebiom.2018.01.011
  7. Schiestl C, Stark GB. Plastische Chirurgie bei Kindern und Jugendlichen. Springer-Verlag 2007.
  8. Hirsch T, Rothoeft T, Teig N, Bauer JW, Pellegrini G, De Rosa L, et al. Regeneration of the entire human epidermis using transgenic stem cells. Nature. 2017;551(7680):327–32. doi:.https://doi.org/10.1038/nature24487
  9. Heydrick S, Roberts E, Kim J, Emani S, Wong JY. Pediatric cardiovascular grafts: historical perspective and future directions. Curr Opin Biotechnol. 2016;40:119–24. doi:.https://doi.org/10.1016/j.copbio.2016.03.013
  10. Martin LY, Ladd MR, Werts A, Sodhi CP, March JC, Hackam DJ. Tissue engineering for the treatment of short bowel syndrome in children. Pediatr Res. 2018;83(1-2):249–57. doi:.https://doi.org/10.1038/pr.2017.234
  11. Hamilton NJ, Kanani M, Roebuck DJ, Hewitt RJ, Cetto R, Culme-Seymour EJ, et al. Tissue-Engineered Tracheal Replacement in a Child: A 4-Year Follow-Up Study. Am J Transplant. 2015;15(10):2750–7. doi:.https://doi.org/10.1111/ajt.13318
  12. Fan W, Gu J, Hu W, Deng A, Ma Y, Liu J, et al. Repairing a 35-mm-long median nerve defect with a chitosan/PGA artificial nerve graft in the human: a case study. Microsurgery. 2008;28(4):238–42. doi:.https://doi.org/10.1002/micr.20488
  13. Hefti F. Kinderorthopädie in der Praxis. 3rd ed, Berlin Heidelberg: Springer-Verlag; 2015.
  14. Commission to the European Parliament and Council. State of Paediatric Medicines in the EU. 10 years of the EU Paediatric Regulation, COM (2017)626. Available from: https://ec.europa.eu/health/sites/health/files/files/paediatrics/docs/2017_childrensmedicines_report_en.pdf
  15. Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006.
  16. Greenberg RG, Corneli A, Bradley J, Farley J, Jafri HS, Lin L, et al. Perceived barriers to pediatrician and family practitioner participation in pediatric clinical trials: Findings from the Clinical Trials Transformation Initiative. Contemp Clin Trials Commun. 2018;9:7–12. doi:.https://doi.org/10.1016/j.conctc.2017.11.006
  17. Greenberg RG, Gamel B, Bloom D, Bradley J, Jafri HS, Hinton D, et al. Parents’ perceived obstacles to pediatric clinical trial participation: Findings from the clinical trials transformation initiative. Contemp Clin Trials Commun. 2018;9:33–9. doi:.https://doi.org/10.1016/j.conctc.2017.11.005
  18. Martin PJ, Uberti JP, Soiffer RJ, Klingemann H, Waller EK, Daly AS, et al. Prochymal Improves Response Rates In Patients With Steroid-Refractory Acute Graft Versus Host Disease (SR-GVHD) Involving The Liver And Gut: Results Of A Randomized, Placebo-Controlled, Multicenter Phase III Trial In GVHD. Biol Blood Marrow Transplant. 2010;16(2):S169–70. doi:.https://doi.org/10.1016/j.bbmt.2009.12.057
  19. Mesoblast Inc. [Internet]. Melbourne: Mesoblast Ltd.; c2016 [cited 2018 Jul 31]. 2018 ASX Announcements 2018 Feb 22: Primary Endpoint Successfully Achieved in MSB P3 GVHD Trial. Available from: http://investorsmedia.mesoblast.com/phoenix.zhtml?c=187006&p=irol-asxnews&nyo=0
  20. Gładysz D, Hozyasz KK. Stem cell regenerative therapy in alveolar cleft reconstruction. Arch Oral Biol. 2015;60(10):1517–32. doi:.https://doi.org/10.1016/j.archoralbio.2015.07.003
  21. Wu C, Pan W, Feng C, Su Z, Duan Z, Zheng Q, et al. Grafting materials for alveolar cleft reconstruction: a systematic review and best-evidence synthesis. Int J Oral Maxillofac Surg. 2018;47(3):345–56. doi:.https://doi.org/10.1016/j.ijom.2017.08.003
  22. Dufrane D, Docquier PL, Delloye C, Poirel HA, André W, Aouassar N. Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction: Clinical Proof of Concept. Medicine (Baltimore). 2015;94(50):e2220. doi:.https://doi.org/10.1097/MD.0000000000002220
  23. Vériter S, André W, Aouassar N, Poirel HA, Lafosse A, Docquier PL, et al. Human Adipose-Derived Mesenchymal Stem Cells in Cell Therapy: Safety and Feasibility in Different “Hospital Exemption” Clinical Applications. PLoS One. 2015;10(10):e0139566. doi:.https://doi.org/10.1371/journal.pone.0139566
  24. Tikkanen J, Leskelä HV, Lehtonen ST, Vähäsarja V, Melkko J, Ahvenjärvi L, et al. Attempt to treat congenital pseudarthrosis of the tibia with mesenchymal stromal cell transplantation. Cytotherapy. 2010;12(5):593–604. doi:.https://doi.org/10.3109/14653249.2010.487898
  25. Granchi D, Devescovi V, Baglio SR, Magnani M, Donzelli O, Baldini N. A regenerative approach for bone repair in congenital pseudarthrosis of the tibia associated or not associated with type 1 neurofibromatosis: correlation between laboratory findings and clinical outcome. Cytotherapy. 2012;14(3):306–14. doi:.https://doi.org/10.3109/14653249.2011.627916
  26. Shaw N, Erickson C, Bryant SJ, Ferguson VL, Krebs MD, Hadley-Miller N, et al. Regenerative Medicine Approaches for the Treatment of Pediatric Physeal Injuries. Tissue Eng Part B Rev. 2018;24(2):85–97. doi:.https://doi.org/10.1089/ten.teb.2017.0274
  27. Innocenti M, Delcroix L, Romano GF, Capanna R. Vascularized epiphyseal transplant. Orthop Clin North Am. 2007;38(1):95–101. doi:.https://doi.org/10.1016/j.ocl.2006.10.003
  28. Stulberg SD, Cooperman DR, Wallensten R. The natural history of Legg-Calvé-Perthes disease. J Bone Joint Surg Am. 1981;63(7):1095–108. doi:.https://doi.org/10.2106/00004623-198163070-00006
  29. Joseph B. Natural history of early onset and late-onset Legg-Calve-Perthes disease. J Pediatr Orthop. 2011;31(2, Suppl):S152–5. doi:.https://doi.org/10.1097/BPO.0b013e318223b423
  30. Chaudhry S, Phillips D, Feldman D. Legg-Calvé-Perthes disease: an overview with recent literature. Bull Hosp Jt Dis (2013). 2014;72(1):18–27.
  31. Bourke G, Ka SPJ. Free phalangeal transfer: donor-site outcome. Br J Plast Surg. 2002;55(4):307–11. doi:.https://doi.org/10.1054/bjps.2002.3836
  32. Garagnani L, Gibson M, Smith PJ, Smith GD. Long-term donor site morbidity after free nonvascularized toe phalangeal transfer. J Hand Surg Am. 2012;37(4):764–74. doi:.https://doi.org/10.1016/j.jhsa.2011.12.010
  33. Kawabata H, Tamura D. Five- and 10-Year Follow-Up of Nonvascularized Toe Phalanx Transfers. J Hand Surg Am. 2018;43(5):485.e1–5. doi:.https://doi.org/10.1016/j.jhsa.2017.10.034
  34. Scotti C, Piccinini E, Takizawa H, Todorov A, Bourgine P, Papadimitropoulos A, et al. Engineering of a functional bone organ through endochondral ossification. Proc Natl Acad Sci USA. 2013;110(10):3997–4002. doi:.https://doi.org/10.1073/pnas.1220108110
  35. Carlier A, Vasilevich A, Marechal M, de Boer J, Geris L. In silico clinical trials for pediatric orphan diseases. Sci Rep. 2018;8(1):2465. doi:.https://doi.org/10.1038/s41598-018-20737-y
  36. Fulco I, Miot S, Haug MD, Barbero A, Wixmerten A, Feliciano S, et al. Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial. Lancet. 2014;384(9940):337–46. doi:.https://doi.org/10.1016/S0140-6736(14)60544-4
  37. Mumme M, Barbero A, Miot S, Wixmerten A, Feliciano S, Wolf F, et al. Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial. Lancet. 2016;388(10055):1985–94. doi:.https://doi.org/10.1016/S0140-6736(16)31658-0
  38. Martin I, Jakob M, Schaefer DJ. From Tissue Engineering to Regenerative Surgery. EBioMedicine. 2018;28:11–2. doi:.https://doi.org/10.1016/j.ebiom.2018.01.029