Editorial
203
Editorial
Regenerative Medicine for the Youngest: Customized Therapies for Rare Diseases Paolo De Coppi1,2 1 Department of Pediatric Surgery, University College London Institute
of Child Health, London, United Kingdom 2 Department of Surgery, Great Ormond Street Hospital for Children,
London, United Kingdom
Stem cells and regenerative medicine are going to change the way we treat patients in the next future.1 Although studies in the field have mainly been conducted to treat degenerative disorders, the results are going to benefit primarily infants and children affected by congenital and acquired disorders.2 This is happening for several reasons. First, the regeneration potential of tissue and organs in young individuals is superior to the one of the elderly and therefore therapies aiming at restoring damaged tissues or organs will be more efficient in the youngest. Second, the group of patients we care for are mostly affected by rare diseases, which frequently require a customized management with the use of prosthesis that are unable to grow with the child. Third, the high costs related to those therapies can be balanced by the long-lasting benefit associated to the treatment of infants and children.2 There are many examples available already describing the success of those therapies in adults and children, and this special issue addresses some of those areas. As pediatric surgeons, the first patient we are involved with is the fetus, when they are affected by a congenital malformation. The fetus is an ideal candidate for therapies aimed at regenerating tissue because they have high plasticity and are capable to engraft efficiently the delivered cells.3 Among the patients, who potentially may benefit best of a prenatal treatment are the ones affected by congenital diaphragmatic hernia,4 both in term of diaphragmatic muscular replacement and lung regeneration. While engineered muscle has still not been applied to human, skin has been successfully engineered for patients.5 Similarly, engineering of bone and cartilage is very advanced and it has been available to patients, though for very limited indications and it is far to be ideal.6 Both tissue engineering and cellular therapeutic applications could also benefit patients affected by urological and nephrological7 or gastrointestinal8 diseases. While urethra, vagina, and bladder prepared in the laboratory using autologous cells have been used in patients, the kidney still remain a major challenge.7
Similarly, the engineer of functional small and large bowel for patients has not been achieved, even if results obtained in small and large animals are quite promising, and may lead in the next future to the possibility of overcoming problems related to short bowel syndrome.8 What is likely to be translated in clinic soon is however the first part of the gut: the esophagus. I also thank the recent advancement on engineering tubular structures such as the trachea9; engineering of esophagus could be adopted in the next future for the treatment of children affected by long-gap esophageal atresia.10 Alternative strategies however to restore tissues which is only partially damaged have also been explored, so it may be possible to regenerate the bowel affected by necrotizing enterocolitis by acting directly on the resident intestinal stem cells instead of substituting the entire intestine.11 Winston Churchill used to say: “It is always wise to look ahead, but difficult to look further than you can see.” We need to be prepared to look through the limited results of regenerative medicine today as an opportunity to revolutionize the way we treat children in the future.
Address for correspondence Paolo De Coppi, MD, PhD, Department of Paediatric Surgery, University College London Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom (e-mail: p. [email protected]).
© 2014 Georg Thieme Verlag KG Stuttgart · New York
References 1 Atala A. Organ preservation, organ and cell transplantation, tissue
2 3
4
5
engineering, and regenerative medicine: the terms may change, but the goals remain the same. Tissue Eng Part A 2014;20(3-4): 445–446 De Coppi P. Regenerative medicine for congenital malformations. J Pediatr Surg 2013;48(2):273–280 Loukogeorgakis SP, Flake AW. In utero stem cell and gene therapy: current status and future perspectives. Eur J Pediatr Surg 2014; 24(3):237–245 Deprest J, Gucciardo L, Eastwood P et al. Medical and regenerative solutions for congenital diaphragmatic hernia: a perinatal perspective. Eur J Pediatr Surg 2014;24(3):270–277 Marino D, Reichmann E, Meuli M. Skingineering. Eur J Pediatr Surg 2014;24(3):205–213
DOI http://dx.doi.org/ 10.1055/s-0034-1378148. ISSN 0939-7248.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Eur J Pediatr Surg 2014;24:203–204.
Editorial 6 Gentili C, Torre M, Cancedda R. Tissue engineering approaches in
9 Elliott MJ, De Coppi P, Speggiorin S, et al. Stem-cell-based, tissue
skeletal pediatric disorders. Eur J Pediatr Surg 2014;24(3): 263–269 7 Garriboli M, Radford A, Southgate J. Regenerative medicine in urology. Eur J Pediatr Surg 2014;24(3):227–236 8 El-Nachef W, Grikscheit T. Enteric nervous system cell replacement therapy for Hirschsprung disease: beyond tissue-engineered intestine. Eur J Pediatr Surg 2014;24(3):214–218
engineered tracheal replacement in a child: a 2-year follow-up study. Lancet 2012;380(9846):994–1000 10 Saxena AK. Esophagus tissue engineering: designing and crafting the components for the “hybrid construct” approach. Eur J Pediatr Surg 2014;24(3):246–262 11 Zani A, De Coppi P. Stem cell therapy as an option for paediatric surgical conditions. Eur J Pediatr Surg 2014;24(3):219–226
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
204
European Journal of Pediatric Surgery
Vol. 24
No. 3/2014
Copyright of European Journal of Pediatric Surgery is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
203
Editorial
Regenerative Medicine for the Youngest: Customized Therapies for Rare Diseases Paolo De Coppi1,2 1 Department of Pediatric Surgery, University College London Institute
of Child Health, London, United Kingdom 2 Department of Surgery, Great Ormond Street Hospital for Children,
London, United Kingdom
Stem cells and regenerative medicine are going to change the way we treat patients in the next future.1 Although studies in the field have mainly been conducted to treat degenerative disorders, the results are going to benefit primarily infants and children affected by congenital and acquired disorders.2 This is happening for several reasons. First, the regeneration potential of tissue and organs in young individuals is superior to the one of the elderly and therefore therapies aiming at restoring damaged tissues or organs will be more efficient in the youngest. Second, the group of patients we care for are mostly affected by rare diseases, which frequently require a customized management with the use of prosthesis that are unable to grow with the child. Third, the high costs related to those therapies can be balanced by the long-lasting benefit associated to the treatment of infants and children.2 There are many examples available already describing the success of those therapies in adults and children, and this special issue addresses some of those areas. As pediatric surgeons, the first patient we are involved with is the fetus, when they are affected by a congenital malformation. The fetus is an ideal candidate for therapies aimed at regenerating tissue because they have high plasticity and are capable to engraft efficiently the delivered cells.3 Among the patients, who potentially may benefit best of a prenatal treatment are the ones affected by congenital diaphragmatic hernia,4 both in term of diaphragmatic muscular replacement and lung regeneration. While engineered muscle has still not been applied to human, skin has been successfully engineered for patients.5 Similarly, engineering of bone and cartilage is very advanced and it has been available to patients, though for very limited indications and it is far to be ideal.6 Both tissue engineering and cellular therapeutic applications could also benefit patients affected by urological and nephrological7 or gastrointestinal8 diseases. While urethra, vagina, and bladder prepared in the laboratory using autologous cells have been used in patients, the kidney still remain a major challenge.7
Similarly, the engineer of functional small and large bowel for patients has not been achieved, even if results obtained in small and large animals are quite promising, and may lead in the next future to the possibility of overcoming problems related to short bowel syndrome.8 What is likely to be translated in clinic soon is however the first part of the gut: the esophagus. I also thank the recent advancement on engineering tubular structures such as the trachea9; engineering of esophagus could be adopted in the next future for the treatment of children affected by long-gap esophageal atresia.10 Alternative strategies however to restore tissues which is only partially damaged have also been explored, so it may be possible to regenerate the bowel affected by necrotizing enterocolitis by acting directly on the resident intestinal stem cells instead of substituting the entire intestine.11 Winston Churchill used to say: “It is always wise to look ahead, but difficult to look further than you can see.” We need to be prepared to look through the limited results of regenerative medicine today as an opportunity to revolutionize the way we treat children in the future.
Address for correspondence Paolo De Coppi, MD, PhD, Department of Paediatric Surgery, University College London Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom (e-mail: p. [email protected]).
© 2014 Georg Thieme Verlag KG Stuttgart · New York
References 1 Atala A. Organ preservation, organ and cell transplantation, tissue
2 3
4
5
engineering, and regenerative medicine: the terms may change, but the goals remain the same. Tissue Eng Part A 2014;20(3-4): 445–446 De Coppi P. Regenerative medicine for congenital malformations. J Pediatr Surg 2013;48(2):273–280 Loukogeorgakis SP, Flake AW. In utero stem cell and gene therapy: current status and future perspectives. Eur J Pediatr Surg 2014; 24(3):237–245 Deprest J, Gucciardo L, Eastwood P et al. Medical and regenerative solutions for congenital diaphragmatic hernia: a perinatal perspective. Eur J Pediatr Surg 2014;24(3):270–277 Marino D, Reichmann E, Meuli M. Skingineering. Eur J Pediatr Surg 2014;24(3):205–213
DOI http://dx.doi.org/ 10.1055/s-0034-1378148. ISSN 0939-7248.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Eur J Pediatr Surg 2014;24:203–204.
Editorial 6 Gentili C, Torre M, Cancedda R. Tissue engineering approaches in
9 Elliott MJ, De Coppi P, Speggiorin S, et al. Stem-cell-based, tissue
skeletal pediatric disorders. Eur J Pediatr Surg 2014;24(3): 263–269 7 Garriboli M, Radford A, Southgate J. Regenerative medicine in urology. Eur J Pediatr Surg 2014;24(3):227–236 8 El-Nachef W, Grikscheit T. Enteric nervous system cell replacement therapy for Hirschsprung disease: beyond tissue-engineered intestine. Eur J Pediatr Surg 2014;24(3):214–218
engineered tracheal replacement in a child: a 2-year follow-up study. Lancet 2012;380(9846):994–1000 10 Saxena AK. Esophagus tissue engineering: designing and crafting the components for the “hybrid construct” approach. Eur J Pediatr Surg 2014;24(3):246–262 11 Zani A, De Coppi P. Stem cell therapy as an option for paediatric surgical conditions. Eur J Pediatr Surg 2014;24(3):219–226
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
204
European Journal of Pediatric Surgery
Vol. 24
No. 3/2014
Copyright of European Journal of Pediatric Surgery is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
