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Chromaffin Progenitor Cells from the Adrenal Medulla

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Abstract

Chromaffin cells of the adrenal medulla are neural crest-derived cells of the sympathoadrenal lineage. Different lines of evidence suggest the existence of a subpopulation of proliferation-competent progenitor cells even in the adult state. The identification of sympathoadrenal progenitors in the adrenal would greatly enhance the understanding of adrenal physiology and their potential role in adrenal pathogenesis. Isolation and differentiation of these progenitor cells in culture would provide a tool to understand their development in vitro. Furthermore, due to the close relation to sympathetic neurons, these cells might provide an expandable source of cells for cell therapy in the treatment of neurodegenerative diseases. We therefore aim to establish protocols for the efficient isolation, enrichment and differentiation of chromaffin progenitor cells to dopaminergic neurons in culture.

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References

  • Anderson DJ (1997) Cellular and molecular biology of neural crest cell lineage determination. Trends Genet 13:276–280

    Article  CAS  PubMed  Google Scholar 

  • Bagga V, Dunnett SB, Fricker-Gates RA (2008) Ascorbic acid increases the number of dopamine neurons in vitro and in transplants to the 6-OHDA-lesioned rat brain. Cell Transplant 17:763–773

    Article  CAS  PubMed  Google Scholar 

  • Beaujean D, Rosenbaum C, Muller HW, Willemsen JJ, Lenders J, Bornstein SR (2003) Combinatorial code of growth factors and neuropeptides define neuroendocrine differentiation in PC12 cells. Exp Neurol 184:348–358

    Article  CAS  PubMed  Google Scholar 

  • Borghese L, Dolezalova D, Opitz T, Haupt S, Leinhaas A, Steinfarz B, Koch P, Edenhofer F, Hampl A, Brustle O (2010) Inhibition of Notch signaling in human embryonic stem cell-derived neural stem cells delays G1/S phase transition and accelerates neuronal differentiation in vitro and in vivo. Stem Cells 28:955–964

    Article  CAS  PubMed  Google Scholar 

  • Bornstein SR, Ehrhart-Bornstein M, Usadel H, Böckmann M, Scherbaum WA (1991) Morphological evidence for a close interaction of chromaffin cells with cortical cells within the adrenal gland. Cell Tissue Res 265:1–9

    Article  CAS  PubMed  Google Scholar 

  • Bornstein SR, González-Hernández JA, Ehrhart-Bornstein M, Adler G, Scherbaum WA (1994) Intimate contact of chromaffin and cortical cells within the human adrenal gland forms the cellular basis for important intraadrenal interactions. J Clin Endocrinol Metab 78:225–232

    Article  CAS  PubMed  Google Scholar 

  • Bottner A, Haidan A, Eisenhofer G, Kristensen K, Castle AL, Scherbaum WA, Schneider H, Chrousos GP, Bornstein SR (2000) Increased body fat mass and suppression of circulating leptin levels in response to hypersecretion of epinephrine in phenylethanolamine-N-methyltransferase (PNMT)-overexpressing mice. Endocrinology 141:4239–4246

    Article  CAS  PubMed  Google Scholar 

  • Brandl C, Florian C, Driemel O, Weber BH, Morsczeck C (2009) Identification of neural crest-derived stem cell-like cells from the corneal limbus of juvenile mice. Exp Eye Res 89:209–217

    Article  CAS  PubMed  Google Scholar 

  • Bylund M, Andersson E, Novitch BG, Muhr J (2003) Vertebrate neurogenesis is counteracted by Sox1–3 activity. Nat Neurosci 6:1162–1168

    Article  CAS  PubMed  Google Scholar 

  • Cepeda C, Walsh JP, Buchwald NA, Levine MS (1991) Neurophysiological maturation of cat caudate neurons: evidence from in vitro studies. Synapse 7:278–290

    Article  CAS  PubMed  Google Scholar 

  • Chung KF, Sicard F, Vukicevic V, Hermann A, Storch A, Huttner WB, Bornstein SR, Ehrhart-Bornstein M (2009) Isolation of neural crest derived chromaffin progenitors from adult adrenal medulla. Stem Cells 27:2602–2613

    Article  CAS  PubMed  Google Scholar 

  • Davies LC, Locke M, Webb RD, Roberts JT, Langley M, Thomas DW, Archer CW, Stephens P (2010) A multipotent neural crest derived progenitor cell population is resident within the oral mucosa lamina propria. Stem Cells Dev 19:819–830

    Article  CAS  PubMed  Google Scholar 

  • Drucker-Colin R, Verdugo-Diaz L (2004) Cell transplantation for Parkinson’s disease: present status. Cell Mol Neurobiol 24:301–316

    Article  CAS  PubMed  Google Scholar 

  • Dupin E, Calloni G, Real C, Goncalves-Trentin A, Le Douarin NM (2007) Neural crest progenitors and stem cells. C R Biol 330:521–529

    Article  CAS  PubMed  Google Scholar 

  • Ehrhart-Bornstein M, Bornstein SR (2008) Cross-talk between adrenal medulla and adrenal cortex in stress. Ann N Y Acad Sci 1148:112–117

    Article  PubMed  Google Scholar 

  • Ehrhart-Bornstein M, Breidert M, Guadanucci P, Wozniak W, Bocian-Sobkowska J, Malendowicz LK, Bornstein SR (1997) 17α-Hydroxylase and chromogranin A in 6th week human fetal adrenals. Horm Metab Res 29:30–32

    Article  CAS  PubMed  Google Scholar 

  • Ehrhart-Bornstein M, Hinson JP, Bornstein SR, Scherbaum WA, Vinson GP (1998) Intraadrenal interactions in the regulation of adrenocortical steroidogenesis. Endocr Rev 19:101–143

    Article  CAS  PubMed  Google Scholar 

  • Ehrhart-Bornstein M, Chung KF, Vukicevic V, Bornstein SR (2009) Is there a role for chromaffin progenitor cells in neurodegenerative diseases? Mol Psychiatry 14:1–4

    Article  CAS  PubMed  Google Scholar 

  • Espejo EF, Gonzalez-Albo MC, Moraes JP, El Banoua F, Flores JA, Caraballo I (2001) Functional regeneration in a rat Parkinson’s model after intrastriatal grafts of glial cell line-derived neurotrophic factor and transforming growth factor beta1-expressing extra-adrenal chromaffin cells of the Zuckerkandl’s organ. J Neurosci 21:9888–9895

    CAS  PubMed  Google Scholar 

  • Feeney DM, Weisend MP, Kline AE (1993) Noradrenergic pharmacotherapy, intracerebral infusion and adrenal transplantation promote functional recovery after cortical damage. J Neural Transplant Plast 4:199–213

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Espejo E, Armengol JA, Flores JA, Galan-Rodriguez B, Ramiro S (2005) Cells of the sympathoadrenal lineage: biological properties as donor tissue for cell-replacement therapies for Parkinson’s disease. Brain Res Brain Res Rev 49:343–354

    Article  CAS  PubMed  Google Scholar 

  • Fliedner SM, Breza J, Kvetnansky R, Powers JF, Tischler AS, Wesley R, Merino M, Lehnert H, Pacak K (2010) Tyrosine hydroxylase, chromogranin A, and steroidogenic acute regulator as markers for successful separation of human adrenal medulla. Cell Tissue Res 340:607–612

    Article  CAS  PubMed  Google Scholar 

  • Forander P, Broberger C, Stromberg I (2001) Glial-cell-line-derived neurotrophic factor induces nerve fibre formation in primary cultures of adrenal chromaffin cells. Cell Tissue Res 305:43–51

    Article  CAS  PubMed  Google Scholar 

  • Galan-Rodriguez B, del-Marco A, Flores JA, Ramiro-Fuentes S, Gonzalez-Aparicio R, Tunez I, Tasset I, Fernandez-Espejo E (2008) Grafts of extra-adrenal chromaffin cells as aggregates show better survival rate and regenerative effects on parkinsonian rats than dispersed cell grafts. Neurobiol Dis 29:529–542

    Article  CAS  PubMed  Google Scholar 

  • Haidan A, Bornstein SR, Glasow A, Uhlmann K, Lübke C, Ehrhart-Bornstein M (1998) Basal steroidogenic activity of adrenocortical cells is increased tenfold by co-culture with chromaffin cells. Endocrinology 139:772–780

    Article  CAS  PubMed  Google Scholar 

  • Haldin CE, LaBonne C (2010) SoxE factors as multifunctional neural crest regulatory factors. Int J Biochem Cell Biol 42:441–444

    Article  CAS  PubMed  Google Scholar 

  • Heese K, Low JW, Inoue N (2006) Nerve growth factor, neural stem cells and Alzheimer’s disease. Neurosignals 15:1–12

    Article  CAS  PubMed  Google Scholar 

  • Hermann A, Maisel M, Wegner F, Liebau S, Kim DW, Gerlach M, Schwarz J, Kim KS, Storch A (2006) Multipotent neural stem cells from the adult tegmentum with dopaminergic potential develop essential properties of functional neurons. Stem Cells 24:949–964

    Article  CAS  PubMed  Google Scholar 

  • Hermann A, List C, Habisch HJ, Vukicevic V, Ehrhart-Bornstein M, Brenner R, Bernstein P, Fickert S, Storch A (2010) Age-dependent neuroectodermal differentiation capacity of human mesenchymal stromal cells: limitations for autologous cell replacement strategies. Cytotherapy 12:17–30

    Article  CAS  PubMed  Google Scholar 

  • Hockberger PE, Tseng HY, Connor JA (1989) Development of rat cerebellar Purkinje cells: electrophysiological properties following acute isolation and in long-term culture. J Neurosci 9:2258–2271

    CAS  PubMed  Google Scholar 

  • Huber K, Bruhl B, Guillemot F, Olson EN, Ernsberger U, Unsicker K (2002) Development of chromaffin cells depends on MASH1 function. Development 129:4729–4738

    CAS  PubMed  Google Scholar 

  • Huber K, Franke A, Bruhl B, Krispin S, Ernsberger U, Schober A, von Bohlen und HO, Rohrer H, Kalcheim C, Unsicker K (2008) Persistent expression of BMP-4 in embryonic chick adrenal cortical cells and its role in chromaffin cell development. Neural Dev 3:28

    Article  PubMed  Google Scholar 

  • Huber K, Kalcheim C, Unsicker K (2009) The development of the chromaffin cell lineage from the neural crest. Auton Neurosci 151:10–16

    Article  CAS  PubMed  Google Scholar 

  • Jozan S, Aziza J, Chatelin S, Evra C, Courtade-Saidi M, Parant O, Sol JC, Zhou H, Lazorthes Y (2007) Human fetal chromaffin cells: a potential tool for cell pain therapy. Exp Neurol 205:525–535

    Article  PubMed  Google Scholar 

  • Kageyama R, Ohtsuka T, Hatakeyama J, Ohsawa R (2005) Roles of bHLH genes in neural stem cell differentiation. Exp Cell Res 306:343–348

    Article  CAS  PubMed  Google Scholar 

  • Krieglstein K, Deimling F, Suter-Crazzolara C, Unsicker K (1996) Expression and localization of GDNF in developing and adult adrenal chromaffin cells. Cell Tissue Res 286:263–268

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Margiotta JF, Howard MJ (2005) BMP4 supports noradrenergic differentiation by a PKA-dependent mechanism. Dev Biol 286:521–536

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Serova L, Kvetnansky R, Sabban EL (2008) Identifying the stress transcriptome in the adrenal medulla following acute and repeated immobilization. Ann N Y Acad Sci 1148:1–28

    Article  CAS  PubMed  Google Scholar 

  • Loring JF, Erickson CA (1987) Neural crest cell migratory pathways in the trunk of the chick embryo. Dev Biol 121:220–236

    Article  CAS  PubMed  Google Scholar 

  • Louvi A, Artavanis-Tsakonas S (2006) Notch signalling in vertebrate neural development. Nat Rev Neurosci 7:93–102

    Article  CAS  PubMed  Google Scholar 

  • Maden M (2007) Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci 8:755–765

    Article  CAS  PubMed  Google Scholar 

  • Madrazo I, Drucker-Colin R, Diaz V, Martinez-Mata J, Torres C, Becerril JJ (1987) Open microsurgical autograft of adrenal medulla to the right caudate nucleus in two patients with intractable Parkinson’s disease. N Engl J Med 316:831–834

    Article  CAS  PubMed  Google Scholar 

  • McCormick DA, Prince DA (1987) Post-natal development of electrophysiological properties of rat cerebral cortical pyramidal neurones. J Physiol 393:743–762

    CAS  PubMed  Google Scholar 

  • Morigushi T, Lim KC, Engel JD (2007) Transcription factor networks specify sympathetic and adrenal chromaffin cell differentiation. Funct Dev Embryol 1:130–135

    Google Scholar 

  • Parlato R, Otto C, Tuckermann J, Stotz S, Kaden S, Grone HJ, Unsicker K, Schutz G (2009) Conditional inactivation of glucocorticoid receptor gene in dopamine-beta-hydroxylase cells impairs chromaffin cell survival. Endocrinology 150:1775–1781

    Article  CAS  PubMed  Google Scholar 

  • Powers JF, Evinger MJ, Zhi J, Picard KL, Tischler AS (2007) Pheochromocytomas in Nf1 knockout mice express a neural progenitor gene expression profile. Neuroscience 147:928–937

    Article  CAS  PubMed  Google Scholar 

  • Quinn NP (1990) The clinical application of cell grafting techniques in patients with Parkinson’s disease. Prog Brain Res 82:619–625

    Article  CAS  PubMed  Google Scholar 

  • Reiprich S, Stolt CC, Schreiner S, Parlato R, Wegner M (2008) SoxE proteins are differentially required in mouse adrenal gland development. Mol Biol Cell 19:1575–1586

    Article  CAS  PubMed  Google Scholar 

  • Sagen J, Castellanos DA, Gajavelli S (2007) Transplants for chronic pain. In: Halberstadt C, Emerich D (eds) Cellular transplantation. From laboratory to clinic. Elsevier, New York, pp 455–475

    Google Scholar 

  • Schaarschmidt G, Schewtschik S, Kraft R, Wegner F, Eilers J, Schwarz J, Schmidt H (2009) A new culturing strategy improves functional neuronal development of human neural progenitor cells. J Neurochem 109:238–247

    Article  CAS  PubMed  Google Scholar 

  • Schober A, Wolf N, Huber K, Hertel R, Krieglstein K, Minichiello L, Kahane N, Widenfalk J, Kalcheim C, Olson L, Klein R, Lewin GR, Unsicker K (1998) TrkB and neurotrophin-4 are important for development and maintenance of sympathetic preganglionic neurons innervating the adrenal medulla. J Neurosci 18:7272–7284

    CAS  PubMed  Google Scholar 

  • Schumm MA, Castellanos DA, Frydel BR, Sagen J (2003) Direct cell-cell contact required for neurotrophic effect of chromaffin cells on neural progenitor cells. Brain Res Dev Brain Res 146:1–13

    Article  CAS  PubMed  Google Scholar 

  • Schumm MA, Castellanos DA, Frydel BR, Sagen J (2004) Improved neural progenitor cell survival when cografted with chromaffin cells in the rat striatum. Exp Neurol 185:133–142

    Article  CAS  PubMed  Google Scholar 

  • Shi F, Corrales CE, Liberman MC, Edge AS (2007) BMP4 induction of sensory neurons from human embryonic stem cells and reinnervation of sensory epithelium. Eur J Neurosci 26:3016–3023

    Article  PubMed  Google Scholar 

  • Sicard F, Ehrhart-Bornstein M, Corbeil D, Sperber S, Krug AW, Ziegler CG, Rettori V, McCann SM, Bornstein SR (2007) Age-dependent regulation of chromaffin cell proliferation by growth factors, dehydroepiandrosterone (DHEA), and DHEA sulfate. Proc Natl Acad Sci USA 104:2007–2012

    Article  CAS  PubMed  Google Scholar 

  • Sorensen DB, Johnsen PF, Bibby BM, Bottner A, Bornstein SR, Eisenhofer G, Pacak K, Hansen AK (2005) PNMT transgenic mice have an aggressive phenotype. Horm Metab Res 37:159–163

    Article  CAS  PubMed  Google Scholar 

  • Sortwell CE, Petty F, Kramer G, Sagen J (1994) In vivo release of catecholamines from xenogeneic chromaffin cell grafts with antidepressive activity. Exp Neurol 130:1–8

    Article  CAS  PubMed  Google Scholar 

  • Storch A, Lester HA, Boehm BO, Schwarz J (2003) Functional characterization of dopaminergic neurons derived from rodent mesencephalic progenitor cells. J Chem Neuroanat 26:133–142

    Article  CAS  PubMed  Google Scholar 

  • Teillet MA, Kalcheim C, Le Douarin NM (1987) Formation of the dorsal root ganglia in the avian embryo: Segmental origin and migratory behavior of neural crest progenitor cells. Dev Biol 120:329–347

    Article  CAS  PubMed  Google Scholar 

  • Tischler AS, Ruzicka LA, Donahue SR, DeLellis RA (1989) Chromaffin cell proliferation in the adult rat adrenal medulla. Int J Dev Neurosci 7:439–448

    Article  CAS  PubMed  Google Scholar 

  • Ulrich-Lai YM, Figueiredo HF, Ostrander MM, Choi DC, Engeland WC, Herman JP (2006) Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner. Am J Physiol Endocrinol Metab 291:E965–E973

    Article  CAS  PubMed  Google Scholar 

  • Unsicker K, Krieglstein K (1996) Growth factors in chromaffin cells. Prog Neurobiol 48:307–324

    Article  CAS  PubMed  Google Scholar 

  • Unsicker K, Huber K, Schutz G, Kalcheim C (2005) The chromaffin cell and its development. Neurochem Res 30:921–925

    Article  CAS  PubMed  Google Scholar 

  • Verhofstad AA (1993) Kinetics of adrenal medullary cells. J Anat 183:315–326

    PubMed  Google Scholar 

  • Widera D, Zander C, Heidbreder M, Kasperek Y, Noll T, Seitz O, Saldamli B, Sudhoff H, Sader R, Kaltschmidt C, Kaltschmidt B (2009) Adult palatum as a novel source of neural crest-related stem cells. Stem Cells 27:1899–1910

    Article  CAS  PubMed  Google Scholar 

  • Wolman M, Cervos-Navarro J, Sampaolo S, Cardesa A (1993) Pathological changes in organs of rats chronically exposed to hypoxia. Development of pulmonary lipidosis. Histol Histopathol 8:247–255

    CAS  PubMed  Google Scholar 

  • Wurtman RJ, Axelrod J (1966) Control of enzymatic synthesis of adrenaline in the adrenal medulla by the adrenal cortical steroids. J Biol Chem 241:2301–2305

    CAS  PubMed  Google Scholar 

  • Yan J, Studer L, McKay RD (2001) Ascorbic acid increases the yield of dopaminergic neurons derived from basic fibroblast growth factor expanded mesencephalic precursors. J Neurochem 76:307–311

    Article  CAS  PubMed  Google Scholar 

  • Yoon K, Gaiano N (2005) Notch signaling in the mammalian central nervous system: insights from mouse mutants. Nat Neurosci 8:709–715

    Article  CAS  PubMed  Google Scholar 

  • Zhou H, Aziza J, Sol JC, Courtade-Saidi M, Chatelin S, Evra C, Parant O, Lazorthes Y, Jozan S (2006) Cell therapy of pain: Characterization of human fetal chromaffin cells at early adrenal medulla development. Exp Neurol 198:370–381

    Article  CAS  PubMed  Google Scholar 

  • Ziegler CG, Sicard F, Lattke P, Bornstein SR, Ehrhart-Bornstein M, Krug AW (2008) Dehydroepiandrosterone induces a neuroendocrine phenotype in nerve growth factor-stimulated chromaffin pheochromocytoma PC12 cells. Endocrinology 149:320–328

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work is supported by the Deutsche Forschungsgemeinschaft (SFB 655 From Cells to Tissues) and through the DFG-Research Center for Regenerative Therapies Dresden (CRTD).

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Correspondence to Monika Ehrhart-Bornstein.

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A commentary to this article can be found at doi:10.1007/s10571-010-9607-8.

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Ehrhart-Bornstein, M., Vukicevic, V., Chung, KF. et al. Chromaffin Progenitor Cells from the Adrenal Medulla. Cell Mol Neurobiol 30, 1417–1423 (2010). https://doi.org/10.1007/s10571-010-9571-3

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