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Published in: Pediatric Surgery International 2/2012

01-02-2012 | Original Article

Smooth muscle proteins from Hirschsprung’s disease facilitates stem cell differentiation

Authors: Cornelia Irene Hagl, Sabine Heumüller, Markus Klotz, Ulrike Subotic, Lucas Wessel, Karl-Herbert Schäfer

Published in: Pediatric Surgery International | Issue 2/2012

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Abstract

Background and aims

The transplantation of neural crest derived stem cells (NCSC’s) is a potent alternative for the treatment of Hirschsprung’s disease (HSCR). Cells to be transplanted should find an appropriate microenvironment to survive and differentiate. To investigate the quality of this microenvironment, effects of HSCR-smooth-muscle-protein extracts upon NCSC’s were studied in vitro.

Methods

Postnatal human gut from children undergoing colonic resection due to HSCR was divided in segments. Smooth muscle was dissected and homogenized. Glial-cell-line-derived-neurotrophic-factor (GDNF) concentration was measured in the homogenates from the individual segment using ELISA. NCSC’s were exposed to protein extracts derived from ganglionic and aganglionic HSCR segments, and their effect upon neurite outgrowth, survival and branching was evaluated.

Results

The amount of the factors varied considerably between the proximal and distal segments, and also from patient to patient. While extracts from proximal segments tended to have more prominent effects, all HSCR-muscle-protein extracts increased neuronal survival and network formation.

Conclusion

Muscle protein from aganglionic bowel supports the survival and outgrowth of NCSC’s and is so an appropriate target for neural stem cell treatment.
Literature
1.
go back to reference Tsuji H, Spitz L, Kiely EM, Drake DP, Pierro A (1999) Management and long-term follow-up of infants with total colonic aganglionosis. J Pediatr Surg 34(1):158–161. pii:S0022-3468(99)90248-8 (discussion 162) Tsuji H, Spitz L, Kiely EM, Drake DP, Pierro A (1999) Management and long-term follow-up of infants with total colonic aganglionosis. J Pediatr Surg 34(1):158–161. pii:S0022-3468(99)90248-8 (discussion 162)
2.
go back to reference Amiel J, Lyonnet S (2001) Hirschsprung disease, associated syndromes, and genetics: a review. J Med Genet 38(11):729–739PubMedCrossRef Amiel J, Lyonnet S (2001) Hirschsprung disease, associated syndromes, and genetics: a review. J Med Genet 38(11):729–739PubMedCrossRef
4.
go back to reference Sandgren K, Ekblad E, Larsson LT (2000) Survival of neurons and interstitial cells of Cajal after autotransplantation of myenteric ganglia from small intestine in the lethal spotted mouse. Pediatr Surg Int 16(4):272–276PubMedCrossRef Sandgren K, Ekblad E, Larsson LT (2000) Survival of neurons and interstitial cells of Cajal after autotransplantation of myenteric ganglia from small intestine in the lethal spotted mouse. Pediatr Surg Int 16(4):272–276PubMedCrossRef
5.
go back to reference Schafer KH, Mestres P (2000) Reaggregation of rat dissociated myenteric plexus in extracellular matrix gels. Dig Dis Sci 45(8):1631–1638PubMedCrossRef Schafer KH, Mestres P (2000) Reaggregation of rat dissociated myenteric plexus in extracellular matrix gels. Dig Dis Sci 45(8):1631–1638PubMedCrossRef
6.
7.
go back to reference Sidebotham EL, Woodward MN, Kenny SE, Lloyd DA, Vaillant CR, Edgar DH (2002) Localization and endothelin-3 dependence of stem cells of the enteric nervous system in the embryonic colon. J Pediatr Surg 37(2):145–150. pii:S0022346802194188 Sidebotham EL, Woodward MN, Kenny SE, Lloyd DA, Vaillant CR, Edgar DH (2002) Localization and endothelin-3 dependence of stem cells of the enteric nervous system in the embryonic colon. J Pediatr Surg 37(2):145–150. pii:S0022346802194188
8.
go back to reference Bondurand N, Natarajan D, Thapar N, Atkins C, Pachnis V (2003) Neuron and glia generating progenitors of the mammalian enteric nervous system isolated from foetal and postnatal gut cultures. Development 130(25):6387–6400. doi:10.1242/dev.00857 PubMedCrossRef Bondurand N, Natarajan D, Thapar N, Atkins C, Pachnis V (2003) Neuron and glia generating progenitors of the mammalian enteric nervous system isolated from foetal and postnatal gut cultures. Development 130(25):6387–6400. doi:10.​1242/​dev.​00857 PubMedCrossRef
10.
go back to reference Schafer KH, Saffrey MJ, Burnstock G, Mestres-Ventura P (1997) A new method for the isolation of myenteric plexus from the newborn rat gastrointestinal tract. Brain Res Brain Res Protoc 1(2):109–113. pii:S1385-299X(96)00017-7 Schafer KH, Saffrey MJ, Burnstock G, Mestres-Ventura P (1997) A new method for the isolation of myenteric plexus from the newborn rat gastrointestinal tract. Brain Res Brain Res Protoc 1(2):109–113. pii:S1385-299X(96)00017-7
11.
go back to reference Schafer KH, Mestres P (1997) Human newborn and adult myenteric plexus grows in different patterns. Cell Mol Biol (Noisy-le-grand) 43(8):1171–1180 Schafer KH, Mestres P (1997) Human newborn and adult myenteric plexus grows in different patterns. Cell Mol Biol (Noisy-le-grand) 43(8):1171–1180
12.
go back to reference Rauch U, Hansgen A, Hagl C, Holland-Cunz S, Schafer KH (2006) Isolation and cultivation of neuronal precursor cells from the developing human enteric nervous system as a tool for cell therapy in dysganglionosis. Int J Colorectal Dis 21(6):554–559. doi:10.1007/s00384-005-0051-z PubMedCrossRef Rauch U, Hansgen A, Hagl C, Holland-Cunz S, Schafer KH (2006) Isolation and cultivation of neuronal precursor cells from the developing human enteric nervous system as a tool for cell therapy in dysganglionosis. Int J Colorectal Dis 21(6):554–559. doi:10.​1007/​s00384-005-0051-z PubMedCrossRef
13.
go back to reference Berrebi D, Fouquet V, de Lagausie P, Carricaburu E, Ferkdadji L, Chomette P, Enezian G, Ezzahir N, Peuchmaur M, Aigrain Y (2007) Duhamel operation vs neonatal transanal endorectal pull-through procedure for Hirschsprung disease: which are the changes for pathologists? J Pediatr Surg 42(4):688–691. doi:10.1016/J.Jpedsurg.2006.12.015 PubMedCrossRef Berrebi D, Fouquet V, de Lagausie P, Carricaburu E, Ferkdadji L, Chomette P, Enezian G, Ezzahir N, Peuchmaur M, Aigrain Y (2007) Duhamel operation vs neonatal transanal endorectal pull-through procedure for Hirschsprung disease: which are the changes for pathologists? J Pediatr Surg 42(4):688–691. doi:10.​1016/​J.​Jpedsurg.​2006.​12.​015 PubMedCrossRef
14.
go back to reference Wang L, Wang ZH, Shen CY, et al (2010) Differentiation of human bone marrow mesenchymal stem cells grown in terpolyesters of 3-hydroxyalkanoates scaffolds into nerve cells. Biomaterials 31:1691–1698 Wang L, Wang ZH, Shen CY, et al (2010) Differentiation of human bone marrow mesenchymal stem cells grown in terpolyesters of 3-hydroxyalkanoates scaffolds into nerve cells. Biomaterials 31:1691–1698
15.
go back to reference Kramer F, Stover T, Warnecke A, et al (2010) BDNF mRNA expression is significantly upregulated in vestibular schwannomas and correlates with proliferative activity. J Neurooncol 98:31–39 Kramer F, Stover T, Warnecke A, et al (2010) BDNF mRNA expression is significantly upregulated in vestibular schwannomas and correlates with proliferative activity. J Neurooncol 98:31–39
16.
go back to reference Bottner M, Bar F, Von Koschitzky H, et al (2010) Laser microdissection as a new tool to investigate site-specific gene expression in enteric ganglia of the human intestine. Neurogastroenterol Motil 22:168–172, e52 Bottner M, Bar F, Von Koschitzky H, et al (2010) Laser microdissection as a new tool to investigate site-specific gene expression in enteric ganglia of the human intestine. Neurogastroenterol Motil 22:168–172, e52
17.
go back to reference Barlow AJ, Wallace AS, Thapar N, Burns AJ (2008) Critical numbers of neural crest cells are required in the pathways from the neural tube to the foregut to ensure complete enteric nervous system formation. Development 135(9):1681–1691. doi:10.1242/dev.017418 PubMedCrossRef Barlow AJ, Wallace AS, Thapar N, Burns AJ (2008) Critical numbers of neural crest cells are required in the pathways from the neural tube to the foregut to ensure complete enteric nervous system formation. Development 135(9):1681–1691. doi:10.​1242/​dev.​017418 PubMedCrossRef
18.
go back to reference Barlow A, de Graaff E, Pachnis V (2003) Enteric nervous system progenitors are coordinately controlled by the G protein-coupled receptor EDNRB and the receptor tyrosine kinase RET. Neuron 40(5):905–916. pii:S089662730300730X Barlow A, de Graaff E, Pachnis V (2003) Enteric nervous system progenitors are coordinately controlled by the G protein-coupled receptor EDNRB and the receptor tyrosine kinase RET. Neuron 40(5):905–916. pii:S089662730300730X
19.
go back to reference Furness J (2006) The enteric nervous system. Blackwell, Oxford Furness J (2006) The enteric nervous system. Blackwell, Oxford
21.
go back to reference Emison ES, Garcia-Barcelo M, Grice EA, Lantieri F, Amiel J, Burzynski G, Fernandez RM, Hao L, Kashuk C, West K, Miao X, Tam PK, Griseri P, Ceccherini I, Pelet A, Jannot AS, de Pontual L, Henrion-Caude A, Lyonnet S, Verheij JB, Hofstra RM, Antinolo G, Borrego S, McCallion AS, Chakravarti A (2010) Differential contributions of rare and common, coding and noncoding Ret mutations to multifactorial Hirschsprung disease liability. Am J Hum Genet 87(1):60–74. doi:10.1016/j.ajhg.2010.06.007 PubMedCrossRef Emison ES, Garcia-Barcelo M, Grice EA, Lantieri F, Amiel J, Burzynski G, Fernandez RM, Hao L, Kashuk C, West K, Miao X, Tam PK, Griseri P, Ceccherini I, Pelet A, Jannot AS, de Pontual L, Henrion-Caude A, Lyonnet S, Verheij JB, Hofstra RM, Antinolo G, Borrego S, McCallion AS, Chakravarti A (2010) Differential contributions of rare and common, coding and noncoding Ret mutations to multifactorial Hirschsprung disease liability. Am J Hum Genet 87(1):60–74. doi:10.​1016/​j.​ajhg.​2010.​06.​007 PubMedCrossRef
24.
go back to reference Metzger M, Caldwell C, Barlow AJ, Burns AJ, Thapar N (2009) Enteric nervous system stem cells derived from human gut mucosa for the treatment of aganglionic gut disorders. Gastroenterology 136(7):2214–2225, e2211–e2213. doi:10.1053/j.gastro.2009.02.048 Metzger M, Caldwell C, Barlow AJ, Burns AJ, Thapar N (2009) Enteric nervous system stem cells derived from human gut mucosa for the treatment of aganglionic gut disorders. Gastroenterology 136(7):2214–2225, e2211–e2213. doi:10.​1053/​j.​gastro.​2009.​02.​048
26.
go back to reference Kruger GM, Mosher JT, Bixby S, Joseph N, Iwashita T, Morrison SJ (2002) Neural crest stem cells persist in the adult gut but undergo changes in self-renewal, neuronal subtype potential, and factor responsiveness. Neuron 35(4):657–669. pii:S0896627302008279 Kruger GM, Mosher JT, Bixby S, Joseph N, Iwashita T, Morrison SJ (2002) Neural crest stem cells persist in the adult gut but undergo changes in self-renewal, neuronal subtype potential, and factor responsiveness. Neuron 35(4):657–669. pii:S0896627302008279
31.
go back to reference Heanue TA, Pachnis V (2007) Enteric nervous system development and Hirschsprung’s disease: advances in genetic and stem cell studies. Nat Rev Neurosci 8(6):466–479. doi:10.1038/nrn2137 PubMedCrossRef Heanue TA, Pachnis V (2007) Enteric nervous system development and Hirschsprung’s disease: advances in genetic and stem cell studies. Nat Rev Neurosci 8(6):466–479. doi:10.​1038/​nrn2137 PubMedCrossRef
32.
go back to reference Parikh DH, Tam PK, Van Velzen D, Edgar D (1992) Abnormalities in the distribution of laminin and collagen type IV in Hirschsprung’s disease. Gastroenterology 102(4 Pt 1):1236–1241. pii:S0016508592001550 Parikh DH, Tam PK, Van Velzen D, Edgar D (1992) Abnormalities in the distribution of laminin and collagen type IV in Hirschsprung’s disease. Gastroenterology 102(4 Pt 1):1236–1241. pii:S0016508592001550
33.
go back to reference Parikh DH, Tam PK, Van Velzen D, Edgar D (1994) The extracellular matrix components, tenascin and fibronectin, in Hirschsprung’s disease: an immunohistochemical study. J Pediatr Surg 29(10):1302–1306. pii:0022-3468(94)90101-5 Parikh DH, Tam PK, Van Velzen D, Edgar D (1994) The extracellular matrix components, tenascin and fibronectin, in Hirschsprung’s disease: an immunohistochemical study. J Pediatr Surg 29(10):1302–1306. pii:0022-3468(94)90101-5
35.
go back to reference Rothman TP, Goldowitz D, Gershon MD (1993) Inhibition of migration of neural crest-derived cells by the abnormal mesenchyme of the presumptive aganglionic bowel of ls/ls mice: analysis with aggregation and interspecies chimeras. Dev Biol 159(2):559–573. doi:10.1006/dbio.1993.1264 PubMedCrossRef Rothman TP, Goldowitz D, Gershon MD (1993) Inhibition of migration of neural crest-derived cells by the abnormal mesenchyme of the presumptive aganglionic bowel of ls/ls mice: analysis with aggregation and interspecies chimeras. Dev Biol 159(2):559–573. doi:10.​1006/​dbio.​1993.​1264 PubMedCrossRef
36.
go back to reference Jacobs-Cohen RJ, Payette RF, Gershon MD, Rothman TP (1987) Inability of neural crest cells to colonize the presumptive aganglionic bowel of ls/ls mutant mice: requirement for a permissive microenvironment. J Comp Neurol 255(3):425–438. doi:10.1002/cne.902550309 PubMedCrossRef Jacobs-Cohen RJ, Payette RF, Gershon MD, Rothman TP (1987) Inability of neural crest cells to colonize the presumptive aganglionic bowel of ls/ls mutant mice: requirement for a permissive microenvironment. J Comp Neurol 255(3):425–438. doi:10.​1002/​cne.​902550309 PubMedCrossRef
37.
go back to reference Martucciello G, Brizzolara A, Favre A, Lombardi L, Bocciardi R, Sanguineti M, Pini Prato A, Jasonni V (2007) Neural crest neuroblasts can colonise aganglionic and ganglionic gut in vivo. Eur J Pediatr Surg 17(1):34–40. doi:10.1055/s-2007-964952 PubMedCrossRef Martucciello G, Brizzolara A, Favre A, Lombardi L, Bocciardi R, Sanguineti M, Pini Prato A, Jasonni V (2007) Neural crest neuroblasts can colonise aganglionic and ganglionic gut in vivo. Eur J Pediatr Surg 17(1):34–40. doi:10.​1055/​s-2007-964952 PubMedCrossRef
38.
go back to reference Ohshiro K, Puri P (1998) Reduced glial cell line-derived neurotrophic factor level in aganglionic bowel in Hirschsprung’s disease. J Pediatr Surg 33(6):904–908. pii:S0022-3468(98)90671-6 Ohshiro K, Puri P (1998) Reduced glial cell line-derived neurotrophic factor level in aganglionic bowel in Hirschsprung’s disease. J Pediatr Surg 33(6):904–908. pii:S0022-3468(98)90671-6
39.
go back to reference Lui VC, Samy ET, Sham MH, Mulligan LM, Tam PK (2002) Glial cell line-derived neurotrophic factor family receptors are abnormally expressed in aganglionic bowel of a subpopulation of patients with Hirschsprung’s disease. Lab Invest 82(6):703–712PubMed Lui VC, Samy ET, Sham MH, Mulligan LM, Tam PK (2002) Glial cell line-derived neurotrophic factor family receptors are abnormally expressed in aganglionic bowel of a subpopulation of patients with Hirschsprung’s disease. Lab Invest 82(6):703–712PubMed
41.
go back to reference Young HM, Hearn CJ, Farlie PG, Canty AJ, Thomas PQ, Newgreen DF (2001) GDNF is a chemoattractant for enteric neural cells. Dev Biol 229(2):503–516. 10.1006/dbio.2000.0100S0012-1606(00)90100-3[pii]PubMedCrossRef Young HM, Hearn CJ, Farlie PG, Canty AJ, Thomas PQ, Newgreen DF (2001) GDNF is a chemoattractant for enteric neural cells. Dev Biol 229(2):503–516. 10.1006/dbio.2000.0100S0012-1606(00)90100-3[pii]PubMedCrossRef
42.
go back to reference Krieglstein K, Henheik P, Farkas L, Jaszai J, Galter D, Krohn K, Unsicker K (1998) Glial cell line-derived neurotrophic factor requires transforming growth factor-beta for exerting its full neurotrophic potential on peripheral and CNS neurons. J Neurosci 18(23):9822–9834PubMed Krieglstein K, Henheik P, Farkas L, Jaszai J, Galter D, Krohn K, Unsicker K (1998) Glial cell line-derived neurotrophic factor requires transforming growth factor-beta for exerting its full neurotrophic potential on peripheral and CNS neurons. J Neurosci 18(23):9822–9834PubMed
44.
go back to reference Schober A, Hertel R, Arumae U, Farkas L, Jaszai J, Krieglstein K, Saarma M, Unsicker K (1999) Glial cell line-derived neurotrophic factor rescues target-deprived sympathetic spinal cord neurons but requires transforming growth factor-beta as cofactor in vivo. J Neurosci 19(6):2008–2015PubMed Schober A, Hertel R, Arumae U, Farkas L, Jaszai J, Krieglstein K, Saarma M, Unsicker K (1999) Glial cell line-derived neurotrophic factor rescues target-deprived sympathetic spinal cord neurons but requires transforming growth factor-beta as cofactor in vivo. J Neurosci 19(6):2008–2015PubMed
45.
go back to reference Parikh DH, Tam PK, Lloyd DA, Van Velzen D, Edgar DH (1992) Quantitative and qualitative analysis of the extracellular matrix protein, laminin, in Hirschsprung’s disease. J Pediatr Surg 27(8):991–995. pii:0022-3468(92)90545-I (discussion 995–996) Parikh DH, Tam PK, Lloyd DA, Van Velzen D, Edgar DH (1992) Quantitative and qualitative analysis of the extracellular matrix protein, laminin, in Hirschsprung’s disease. J Pediatr Surg 27(8):991–995. pii:0022-3468(92)90545-I (discussion 995–996)
46.
go back to reference Bhattacharyya A, Oppenheim R, Prevette D, Moore B, Brackenbury RNR (1992) S100 is present in developing chicken neurons and Schwann cells and promotes motor neuron survival in vivo. J Neurobiol 23(4):451–466. doi:10.1002/neu.480230410 PubMedCrossRef Bhattacharyya A, Oppenheim R, Prevette D, Moore B, Brackenbury RNR (1992) S100 is present in developing chicken neurons and Schwann cells and promotes motor neuron survival in vivo. J Neurobiol 23(4):451–466. doi:10.​1002/​neu.​480230410 PubMedCrossRef
47.
go back to reference Ellis EF, Willoughby KA, Sparks SA, Chen T (2007) S100B protein is released from rat neonatal neurons, astrocytes, and microglia by in vitro trauma and anti-S100 increases trauma-induced delayed neuronal injury and negates the protective effect of exogenous S100B on neurons. J Neurochem 101(6):1463–1470. doi:10.1111/j.1471-4159.2007.04515.x PubMedCrossRef Ellis EF, Willoughby KA, Sparks SA, Chen T (2007) S100B protein is released from rat neonatal neurons, astrocytes, and microglia by in vitro trauma and anti-S100 increases trauma-induced delayed neuronal injury and negates the protective effect of exogenous S100B on neurons. J Neurochem 101(6):1463–1470. doi:10.​1111/​j.​1471-4159.​2007.​04515.​x PubMedCrossRef
50.
go back to reference Gazzolo D, Florio P, Zullino E, Giovannini L, Scopesi F, Bellini C, Peri V, Mezzano P, Petraglia F, Michetti F (2010) S100B protein increases in human blood and urine during stressful activity. Clin Chem Lab Med 48(9):1363–1365. doi:10.1515/CCLM.2010.262 PubMedCrossRef Gazzolo D, Florio P, Zullino E, Giovannini L, Scopesi F, Bellini C, Peri V, Mezzano P, Petraglia F, Michetti F (2010) S100B protein increases in human blood and urine during stressful activity. Clin Chem Lab Med 48(9):1363–1365. doi:10.​1515/​CCLM.​2010.​262 PubMedCrossRef
51.
go back to reference Lindley RM, Hawcutt DB, Connell MG, Almond SL, Vannucchi MG, Faussone-Pellegrini MS, Edgar DH, Kenny SE (2008) Human and mouse enteric nervous system neurosphere transplants regulate the function of aganglionic embryonic distal colon. Gastroenterology 135(1):205–216, e206. doi:10.1053/j.gastro.2008.03.035 Lindley RM, Hawcutt DB, Connell MG, Almond SL, Vannucchi MG, Faussone-Pellegrini MS, Edgar DH, Kenny SE (2008) Human and mouse enteric nervous system neurosphere transplants regulate the function of aganglionic embryonic distal colon. Gastroenterology 135(1):205–216, e206. doi:10.​1053/​j.​gastro.​2008.​03.​035
Metadata
Title
Smooth muscle proteins from Hirschsprung’s disease facilitates stem cell differentiation
Authors
Cornelia Irene Hagl
Sabine Heumüller
Markus Klotz
Ulrike Subotic
Lucas Wessel
Karl-Herbert Schäfer
Publication date
01-02-2012
Publisher
Springer-Verlag
Published in
Pediatric Surgery International / Issue 2/2012
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI
https://doi.org/10.1007/s00383-011-3010-5

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