Skip to main content

Advertisement

SpringerLink
Log in

Stem Cell Therapy in Neonatal Diseases

  • Review Article
  • Published:
The Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Common complications in neonates occur in almost every organ system in the neonatal intensive care unit. While a number of them have short-term effects, a few of them also have long-term consequences. Among the latter are bronchopulmonary dysplasia and necrotizing enterocolitis in premature neonates, and hypoxic ischemic encephalopathy in borderline preterm and term neonates. While medical advances have improved our understanding of the pathogenesis, therapies to effectively prevent and/or significantly ameliorate the severity of these disorders, and to decrease their associated mortality and morbidity have not been found. One promising approach to make a potential impact in the outcomes of these neonatal conditions is the use stem cells, specifically, mesenchymal stem cells. The authors briefly review the potential role of stem cell therapy in the above-mentioned neonatal diseases. They focus primarily on human clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ramalho-Santos M, Willenbring H. On the origin of the term “stem cell”. Cell Stem Cell. 2007;1:35–8.

    Article  CAS  PubMed  Google Scholar 

  2. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–7.

    Article  CAS  PubMed  Google Scholar 

  3. Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–20.

    Article  CAS  PubMed  Google Scholar 

  4. Blum B, Benvenisty N. The tumorigenicity of human embryonic stem cells. Adv Cancer Res. 2008;100:133–58.

    PubMed  Google Scholar 

  5. Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991;9:641–50.

    Article  CAS  PubMed  Google Scholar 

  6. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–7.

    Article  CAS  PubMed  Google Scholar 

  7. Noel D, Djouad F, Bouffi C, Mrugala D, Jorgensen C. Multipotent mesenchymal stromal cells and immune tolerance. Leuk Lymphoma. 2007;48:1283–9.

    Article  CAS  PubMed  Google Scholar 

  8. Javed MJ, Mead LE, Prater D, et al. Endothelial colony forming cells and mesenchymal stem cells are enriched at different gestational ages in human umbilical cord blood. Pediatr Res. 2008;64:68–73.

    Article  PubMed  Google Scholar 

  9. Bizzarro MJ, Bhandari V, Krause DS, Smith BR, Gross I. Circulating stem cells in extremely preterm neonates. Acta Paediatr. 2007;96:521–5.

    Article  PubMed  Google Scholar 

  10. Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol. 2000;28:875–84.

    Article  CAS  PubMed  Google Scholar 

  11. Bhandari A, Bhandari V. Pathogenesis, pathology and pathophysiology of pulmonary sequelae of bronchopulmonary dysplasia in premature infants. Front Biosci. 2003;8:e370–80.

    Article  CAS  PubMed  Google Scholar 

  12. Bhandari A, McGrath-Morrow S. Long-term pulmonary outcomes of patients with bronchopulmonary dysplasia. Semin Perinatol. 2013;37:132–7.

    Article  PubMed  Google Scholar 

  13. Balasubramaniam V, Mervis CF, Maxey AM, Markham NE, Abman SH. Hyperoxia reduces bone marrow, circulating, and lung endothelial progenitor cells in the developing lung: implications for the pathogenesis of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2007;292:L1073–84.

    Article  CAS  PubMed  Google Scholar 

  14. Popova AP, Bozyk PD, Bentley JK, et al. Isolation of tracheal aspirate mesenchymal stromal cells predicts bronchopulmonary dysplasia. Pediatrics. 2010;126:e1127–33.

    Article  PubMed  Google Scholar 

  15. Hennrick KT, Keeton AG, Nanua S, et al. Lung cells from neonates show a mesenchymal stem cell phenotype. Am J Respir Crit Care Med. 2007;175:1158–64.

    Article  CAS  PubMed  Google Scholar 

  16. O’Reilly M, Thebaud B. The promise of stem cells in bronchopulmonary dysplasia. Semin Perinatol. 2013;37:79–84.

    Article  PubMed  Google Scholar 

  17. Tian ZF, Du J, Wang B, Hong XY, Feng ZC. Intravenous infusion of rat bone marrow-derived mesenchymal stem cells ameliorates hyperoxia-induced lung injury in neonatal rats. Nan Fang Yi Ke Da Xue Xue Bao. 2007;27:1692–5.

    CAS  PubMed  Google Scholar 

  18. Zhang X, Wang H, Shi Y, et al. Role of bone marrow-derived mesenchymal stem cells in the prevention of hyperoxia-induced lung injury in newborn mice. Cell Biol Int. 2012;36:589–94.

    Article  CAS  PubMed  Google Scholar 

  19. Aslam M, Baveja R, Liang OD, et al. Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. Am J Respir Crit Care Med. 2009;180:1122–30.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Fung ME, Thebaud B. Stem cell-based therapy for neonatal lung disease: it is in the juice. Pediatr Res. 2014;75:2–7.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Biancone L, Bruno S, Deregibus MC, Tetta C, Camussi G. Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrol Dial Transplant. 2012;27:3037–42.

    Article  CAS  PubMed  Google Scholar 

  22. Johnstone RM. Exosomes biological significance: a concise review. Blood Cells Mol Dis. 2006;36:315–21.

    Article  CAS  PubMed  Google Scholar 

  23. Chang YS, Ahn SY, Yoo HS, et al. Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr. 2014;164:966–72.e6.

    Article  PubMed  Google Scholar 

  24. Fauza DO. Tissue engineering in congenital diaphragmatic hernia. Semin Pediatr Surg. 2014;23:135–40.

    Article  PubMed  Google Scholar 

  25. Yuniartha R, Alatas FS, Nagata K, et al. Therapeutic potential of mesenchymal stem cell transplantation in a nitrofen-induced congenital diaphragmatic hernia rat model. Pediatr Surg Int. 2014;30:907–14.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  27. Liao Y, Cotten M, Tan S, Kurtzberg J, Cairo MS. Rescuing the neonatal brain from hypoxic injury with autologous cord blood. Bone Marrow Transplant. 2013;48:890–900.

    Article  CAS  PubMed  Google Scholar 

  28. Chicha L, Smith T, Guzman R. Stem cells for brain repair in neonatal hypoxia-ischemia. Childs Nerv Syst. 2014;30:37–46.

    Article  CAS  PubMed  Google Scholar 

  29. Mancias-Guerra C, Marroquin-Escamilla AR, Gonzalez-Llano O, et al. Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial. Cytotherapy. 2014;16:810–20.

    Article  CAS  PubMed  Google Scholar 

  30. Wang X, Cheng H, Hua R, et al. Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: a preliminary clinical study. Cytotherapy. 2013;15:1549–62.

    Article  PubMed  Google Scholar 

  31. Min K, Song J, Kang JY, et al. Umbilical cord blood therapy potentiated with erythropoietin for children with cerebral palsy: a double-blind, randomized, placebo-controlled trial. Stem Cells. 2013;31:581–91.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Cotten CM, Murtha AP, Goldberg RN, et al. Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. J Pediatr. 2014;164:973–9.e1.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Tayman C, Uckan D, Kilic E, et al. Mesenchymal stem cell therapy in necrotizing enterocolitis: a rat study. Pediatr Res. 2011;70:489–94.

    Article  PubMed  Google Scholar 

  34. Zani A, Cananzi M, Fascetti-Leon F, et al. Amniotic fluid stem cells improve survival and enhance repair of damaged intestine in necrotising enterocolitis via a COX-2 dependent mechanism. Gut. 2014;63:300–9.

    CAS  PubMed  Google Scholar 

Download references

Contributions

CG: Initial draft, revisions and final draft; VB: Concept, revisions and final draft. VB will act as guarantor for this paper.

Conflict of Interest

None.

Source of Funding

None.

Author information

Authors and Affiliations

  1. Division of Perinatal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Child Health Research Center, Yale University School of Medicine, 464 Congress Avenue, New Haven, CT, 06520, USA

    Ciprian P. Gheorghe & Vineet Bhandari

  2. Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA, 19134, USA

    Vineet Bhandari

Authors
  1. Ciprian P. Gheorghe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vineet Bhandari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vineet Bhandari.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gheorghe, C.P., Bhandari, V. Stem Cell Therapy in Neonatal Diseases. Indian J Pediatr 82, 637–641 (2015). https://doi.org/10.1007/s12098-015-1739-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-015-1739-x

Keywords

Search

Navigation