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Stammzelltherapien in der Neonatologie

Stem cell therapy in neonatology

  • Leitthema
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Zusammenfassung

Hintergrund

In rezenten Veröffentlichungen wurde die Stammzelltherapie bei Frühgeborenen mit drohender bronchopulmonaler Dysplasie (BPD) und bei reifen Neugeborenen mit schwerer hypoxisch-ischämischer Enzephalopathie (HIE) beschrieben.

Ziel der Arbeit

Diese Erstbeschreibungen geben Anlass, die Chancen und Risiken der Stammzelltherapie in der Neonatologie zu beleuchten. Hierzu wird über die bisherige Entwicklung und Perspektiven der Stammzelltherapie bei neonatalen Erkrankungen ein Überblick gegeben.

Material und Methoden

Auf der Grundlage einer Suche in PubMed nach regenerativen Therapieformen in der Neonatologie wurden Studien identifiziert, die im Folgenden in den Kategorien „experimentelle Studien“ und „klinische Studien“ aufgeführt werden. Hierbei wurde einleitend schon auf die oben erwähnten ersten publizierten Studien eingegangen.

Ergebnisse

Die Pilotstudien waren aufbauend auf tierexperimentellen Studien konzipiert worden, in denen u. a. die optimale Zellfraktion, die Zellzahl und der Applikationszeitraum sowohl bei drohender BPD als auch bei einer HIE untersucht wurden. Hierbei zeigten sich im klassischen Modell der BPD, induziert durch eine postnatale Hyperoxie, eine Verbesserung der histologischen Lungenbefunde im Sinne einer fortgesetzten Alveolarisierung und verminderten inflammatorischen Reaktion, im Vergleich zu Kontrolltieren. Diese Untersuchungen wurden meist mit neonatalen Nagern in einem terminal sakkulären Lungenentwicklungsstadium durchgeführt. Bei experimentell induzierter HIE waren Stammzellen in der Lage, die histologischen Charakteristika dieser Schädigung zu vermindern und in funktionellen Untersuchungen einen präventiven Effekt zu zeigen.

Schlussfolgerungen

Offene Fragen der eingangs zitierten klinischen Studien betreffen u. a. die Wahl zwischen autologen und allogenen Therapieansätzen. Des Weiteren bleibt zu evaluieren, inwieweit mesenchymale oder andere Stammzellfraktionen bzw. mononukleäre Zellen die sicherste und effizienteste Therapiemethode darstellen. Hierzu sind klinisch-kontrollierte Studien, einschließlich Nachsorgestudien, u. a. mit Evaluation des Zielorgans, der Immunfunktion und der allgemeinen Entwicklung, notwendig, bis Stammzelltherapien in die Neonatologie Eingang finden können.

Abstract

Background

In recent publications stem cell therapy was described in preterm neonates with impending bronchopulmonary dysplasia (BPD) and in term newborns with severe hypoxic-ischemic encephalopathy (HIE).

Aim

These first descriptions formed the basis to evaluate risks and benefits of stem cell therapy and other forms of regenerative therapy in neonatology. An overview of the development and perspectives of stem cell therapy for severe neonatal diseases is given.

Material and methods

Based on a search in PubMed for regenerative therapies in neonatology, studies were identified which were carried out in the categories experimental and clinical studies. The first published studies are described as a form of introduction.

Results

These pilot studies were based on experimental animal studies which were carried out to optimize cell fractions, numbers of cells as well as timing in impending BPD and HIE. In experimental BPD induced by postnatal hyperoxia an improvement in lung histology indicating sustained alveolarization and reduced inflammatory reactions compared with controls was induced by stem cells. The investigations were carried out mostly with neonatal rodents in a terminal saccular lung development stage. In experimentally induced HIE, stem cells mostly mesenchymal stem cells, were effective in reducing the histological characteristics of the insult which was reflected by improved functional testing results.

Conclusion

Open questions after publication of both phase I trials concern among others the optimum type of stem cells and whether to use autologous or allogeneic therapy. Furthermore, it remains to be evaluated how far mesenchymal stem cells or other stem cell fractions and alternatively mononuclear cells are the most effective and safest therapy in neonates. Furthermore, apart from larger controlled clinical trials, follow-up studies are mandatory to assess the specific organ development and immune function and overall development of neonates enrolled in these trials. This approach can only be used as a standard in neonatal care after proving the safety and efficacy of stem cell therapy in neonates.

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Literatur

  1. Ahn SY, Chang YS, Sung DK et al (2013) Mesenchymal stem cells prevent hydrocephalus after severe intraventricular hemorrhage. Stroke 44:497–504

    Article  CAS  PubMed  Google Scholar 

  2. Aktas M, Buchheiser A, Houben A et al (2010) Good manufacturing practice-grade production of unrestricted somatic stem cell from fresh cord blood. Cytotherapy 12:338–348

    Article  CAS  PubMed  Google Scholar 

  3. Aslam M, Baveja R, Liang OD et al (2009) Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. Am J Respir Crit Care Med 180:1122–1130

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Bennet L, Tan S, Van den Heuij L et al (2012) Cell therapy for neonatal hypoxia-ischemia and cerebral palsy. Ann Neurol 71:589–600

    Article  PubMed  Google Scholar 

  5. Chang YS, Ahn SY, Yoo HS et al (2014) Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr 164:966–972.e6

    Article  PubMed  Google Scholar 

  6. Chang YS, Choi SJ, Ahn SY et al (2013) Timing of umbilical cord blood derived mesenchymal stem cells transplantation determines therapeutic efficacy in the neonatal hyperoxic lung injury. PLoS One 8:e52419

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Chang YS, Oh W, Choi SJ et al (2009) Human umbilical cord blood-derived mesenchymal stem cells attenuate hyperoxia-induced lung injury in neonatal rats. Cell Transplant 18:869–886

    Article  PubMed  Google Scholar 

  8. Cotten CM, Murtha AP, Goldberg RN et al (2014) Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. J Pediatr 164:973–979.e1

    Article  PubMed  Google Scholar 

  9. Crompton KE, Elwood N, Kirkland M et al (2014) Feasibility of trialling cord blood stem cell treatments for cerebral palsy in Australia. J Paediatr Child Health. DOI 10.1111/jpc.12618

  10. Flemmer AW, Maier RF, Hummler H (2014) Treatment of neonatal asphyxia with a special focus on therapeutic hypothermia. Klin Padiatr 226:29–37

    Article  CAS  PubMed  Google Scholar 

  11. Gortner L, Felderhoff-Muser U, Monz D et al (2012) Regenerative therapies in neonatology: clinical perspectives. Klin Padiatr 224:233–240

    Article  CAS  PubMed  Google Scholar 

  12. Gortner L, Misselwitz B, Milligan D et al (2011) Rates of bronchopulmonary dysplasia in very preterm neonates in Europe: results from the MOSAIC cohort. Neonatology 99:112–117

    Article  PubMed  Google Scholar 

  13. Gortner L, Monz D, Mildau C et al (2013) Bronchopulmonary dysplasia in a double-hit mouse model induced by intrauterine hypoxia and postnatal hyperoxia: closer to clinical features? Ann Anat 195:351–358

    Article  PubMed  Google Scholar 

  14. Kaneko Y, Tajiri N, Su TP et al (2012) Combination treatment of hypothermia and mesenchymal stromal cells amplifies neuroprotection in primary rat neurons exposed to hypoxic-ischemic-like injury in vitro: role of the opioid system. PLoS One 7:e47583

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Kim SU (2014) Lysosomal storage diseases: stem cell-based cell- and gene-therapy. Cell Transplant. DOI

  16. Kourembanas S (2014) Stem cell-based therapy for newborn lung and brain injury: feasible, safe, and the next therapeutic breakthrough? J Pediatr 164:954–956

    Article  PubMed  Google Scholar 

  17. Luan Z, Liu W, Qu S et al (2012) Effects of neural progenitor cell transplantation in children with severe cerebral palsy. Cell Transplant 21(Suppl 1): 91–98

    Article  Google Scholar 

  18. Ludwig AK, Giebel B (2012) Exosomes: small vesicles participating in intercellular communication. Int J Biochem Cell Biol 44:11–15

    Article  CAS  PubMed  Google Scholar 

  19. Meyburg J, Hoffmann GF (2010) Liver, liver cell and stem cell transplantation for the treatment of urea cycle defects. Mol Genet Metab 100(Suppl 1): 77–83

    Article  Google Scholar 

  20. Monz D, Tutdibi E, Mildau C et al (2013) Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice. PLoS One 8:e74740

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Pham PV, Vu NB, Pham VM et al (2014) Good manufacturing practice-compliant isolation and culture of human umbilical cord blood-derived mesenchymal stem cells. J Transl Med 12:56

    Article  PubMed Central  PubMed  Google Scholar 

  22. Phillips AW, Johnston MV, Fatemi A (2013) The potential for cell-based therapy in perinatal brain injuries. Transl Stroke Res 4:137–148

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Rizvanov AA, Kiyasov AP, Gaziziov IM et al (2008) Human umbilical cord blood cells transfected with VEGF and L(1)CAM do not differentiate into neurons but transform into vascular endothelial cells and secrete neuro-trophic factors to support neuro-genesis-a novel approach in stem cell therapy. Neurochem Int 53:389–394

    Article  CAS  PubMed  Google Scholar 

  24. Scafidi J, Hammond TR, Scafidi S et al (2014) Intranasal epidermal growth factor treatment rescues neonatal brain injury. Nature 506:230–234

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Van Haaften T, Byrne R, Bonnet S et al (2009) Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats. Am J Respir Crit Care Med 180:1131–1142

    Article  Google Scholar 

  26. Van Velthoven CT, Kavelaars A, Van Bel F et al (2010) Mesenchymal stem cell treatment after neonatal hypoxic-ischemic brain injury improves behavioral outcome and induces neuronal and oligodendrocyte regeneration. Brain Behav Immun 24:387–393

    Article  Google Scholar 

  27. Van Velthoven CT, Kavelaars A, Van Bel F et al (2010) Repeated mesenchymal stem cell treatment after neonatal hypoxia-ischemia has distinct effects on formation and maturation of new neurons and oligodendrocytes leading to restoration of damage, corticospinal motor tract activity, and sensorimotor function. J Neurosci 30:9603–9611

    Article  Google Scholar 

  28. Yasuhara T, Hara K, Maki M et al (2008) Intravenous grafts recapitulate the neurorestoration afforded by intracerebrally delivered multipotent adult progenitor cells in neonatal hypoxic-ischemic rats. J Cereb Blood Flow Metab 28:1804–1810

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Zhang X, Wang H, Shi Y et al (2012) Role of bone marrow-derived mesenchymal stem cells in the prevention of hyperoxia-induced lung injury in newborn mice. Cell Biol Int 36:589–594

    Article  CAS  PubMed  Google Scholar 

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Einhaltung ethischer Richtlinien

Interessenkonflikt. L. Gortner, S. Meyer sowie E. Tutdibi geben an, dass kein Interessenkonflikt besteht. Der Beitrag enthält keine Studien an Menschen oder Tieren

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Authors and Affiliations

  1. Klinik für Allgemeine Pädiatrie und Neonatologie, Universitätsklinikum des Saarlandes, Kirrberger Str., 66421, Homburg/Saar, Deutschland

    L. Gortner, S. Meyer & E. Tutdibi

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  1. L. Gortner
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  2. S. Meyer
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  3. E. Tutdibi
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Correspondence to L. Gortner.

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Gortner, L., Meyer, S. & Tutdibi, E. Stammzelltherapien in der Neonatologie. Monatsschr Kinderheilkd 162, 792–797 (2014). https://doi.org/10.1007/s00112-014-3108-7

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  • DOI: https://doi.org/10.1007/s00112-014-3108-7

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