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Other Tissues-Derived Mesenchymal Stem Cells for Perinatal Brain Injury

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Book cover Cell Therapy for Perinatal Brain Injury

Abstract

Cell-based treatments are emerging as a potential therapy for perinatal brain injury. Neural stem/progenitor cells (NSPCs) have been studied primarily in preclinical models of HIE. However, despite their neural commitment, ethical concerns hinder the use of postmortem human brains as a source of NSPCs in future clinical applications. Furthermore, intracerebral administration is an invasive procedure.

Stem cells originating from nonneural tissues can provide an approach that avoids these limitations. The stem cells from nonneural tissues, such as umbilical cord blood cells (UCBCs) and mesenchymal stem cells (MSCs), have a broad potential for differentiation, into mesodermal, endodermal, and ectodermal lineages.

UCBCs have an advantage in that we can perform autologous transplantation if we get them at birth; however, it is conceivable that we might often encounter difficulties collecting UCBCs in emergency situations.

MSCs can be used as alternative cells for the treatment of perinatal HIE because we can use allogeneic MSCs. In this chapter, I describe preclinical studies with various origins of MSCs as well as clinical studies.

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References

  1. Bennet L, Tan S, Van den Heuij L, Derrick M, Groenendaal F, van Bel F, et al. Cell therapy for neonatal hypoxia-ischemia and cerebral palsy. Ann Neurol. 2012;71(5):589–600. https://doi.org/10.1002/ana.22670.

    Article  PubMed  Google Scholar 

  2. Titomanlio L, Kavelaars A, Dalous J, Mani S, El Ghouzzi V, Heijnen C, et al. Stem cell therapy for neonatal brain injury: perspectives and challenges. Ann Neurol. 2011;70(5):698–712. https://doi.org/10.1002/ana.22518.

    Article  PubMed  Google Scholar 

  3. Felling RJ, Snyder MJ, Romanko MJ, Rothstein RP, Ziegler AN, Yang Z, et al. Neural stem/progenitor cells participate in the regenerative response to perinatal hypoxia/ischemia. J Neurosci. 2006;26(16):4359–69. https://doi.org/10.1523/JNEUROSCI.1898-05.2006.

    Article  CAS  PubMed  Google Scholar 

  4. Sato Y, Nakanishi K, Hayakawa M, Kakizawa H, Saito A, Kuroda Y, et al. Reduction of brain injury in neonatal hypoxic-ischemic rats by intracerebroventricular injection of neural stem/progenitor cells together with chondroitinase ABC. Reprod Sci. 2008;15(6):613–20. https://doi.org/10.1177/1933719108317299.

    Article  PubMed  Google Scholar 

  5. Sato Y, Oohira A. Chondroitin sulfate, a major niche substance of neural stem cells, and cell transplantation therapy of neurodegeneration combined with niche modification. Curr Stem Cell Res Ther. 2009;4(3):200–9.

    Article  CAS  PubMed  Google Scholar 

  6. Sato Y, Shinjyo N, Sato M, Osato K, Zhu C, Pekna M, et al. Grafting of neural stem and progenitor cells to the hippocampus of young, irradiated mice causes gliosis and disrupts the granule cell layer. Cell Death Dis. 2013;4:e591. https://doi.org/10.1038/cddis.2013.92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy. 2005;7(1):36–45. https://doi.org/10.1080/14653240510018118.

    Article  PubMed  Google Scholar 

  8. Zangi L, Margalit R, Reich-Zeliger S, Bachar-Lustig E, Beilhack A, Negrin R, et al. Direct imaging of immune rejection and memory induction by allogeneic mesenchymal stromal cells. Stem Cells. 2009;27(11):2865–74. https://doi.org/10.1002/stem.217.

    Article  CAS  PubMed  Google Scholar 

  9. van Velthoven CT, Kavelaars A, Heijnen CJ. Mesenchymal stem cells as a treatment for neonatal ischemic brain damage. Pediatr Res. 2012a;71(4 Pt 2):474–81. https://doi.org/10.1038/pr.2011.64.

    Article  PubMed  Google Scholar 

  10. Donega V, Nijboer CH, Braccioli L, Slaper-Cortenbach I, Kavelaars A, van Bel F, et al. Intranasal administration of human MSC for ischemic brain injury in the mouse: in vitro and in vivo neuroregenerative functions. PLoS One. 2014a;9(11):e112339. https://doi.org/10.1371/journal.pone.0112339.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Yasuhara T, Matsukawa N, Yu G, Xu L, Mays RW, Kovach J, et al. Behavioral and histological characterization of intrahippocampal grafts of human bone marrow-derived multipotent progenitor cells in neonatal rats with hypoxic-ischemic injury. Cell Transplant. 2006;15(3):231–8.

    Article  PubMed  Google Scholar 

  12. Yasuhara T, Hara K, Maki M, Mays RW, Deans RJ, Hess DC, et al. Intravenous grafts recapitulate the neurorestoration afforded by intracerebrally delivered multipotent adult progenitor cells in neonatal hypoxic-ischemic rats. J Cereb Blood Flow Metab. 2008;28(11):1804–10. https://doi.org/10.1038/jcbfm.2008.68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ. Mesenchymal stem cell treatment after neonatal hypoxic-ischemic brain injury improves behavioral outcome and induces neuronal and oligodendrocyte regeneration. Brain Behav Immun. 2010a;24(3):387–93. https://doi.org/10.1016/j.bbi.2009.10.017.

    Article  PubMed  Google Scholar 

  14. van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ. 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. 2010c;30(28):9603–11. https://doi.org/10.1523/JNEUROSCI.1835-10.2010.

    Article  PubMed  Google Scholar 

  15. van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ. Mesenchymal stem cell transplantation changes the gene expression profile of the neonatal ischemic brain. Brain Behav Immun. 2011;25(7):1342–8. https://doi.org/10.1016/j.bbi.2011.03.021.

    Article  PubMed  Google Scholar 

  16. van Velthoven CT, van de Looij Y, Kavelaars A, Zijlstra J, van Bel F, Huppi PS, et al. Mesenchymal stem cells restore cortical rewiring after neonatal ischemia in mice. Ann Neurol. 2012b;71(6):785–96. https://doi.org/10.1002/ana.23543.

    Article  PubMed  Google Scholar 

  17. Gu Y, Zhang Y, Bi Y, Liu J, Tan B, Gong M, et al. Mesenchymal stem cells suppress neuronal apoptosis and decrease IL-10 release via the TLR2/NFkappaB pathway in rats with hypoxic-ischemic brain damage. Mol Brain. 2015;8(1):65. https://doi.org/10.1186/s13041-015-0157-3.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Gu Y, He M, Zhou X, Liu J, Hou N, Bin T, et al. Endogenous IL-6 of mesenchymal stem cell improves behavioral outcome of hypoxic-ischemic brain damage neonatal rats by supressing apoptosis in astrocyte. Sci Rep. 2016;6:18587. https://doi.org/10.1038/srep18587.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lee JA, Kim BI, Jo CH, Choi CW, Kim EK, Kim HS, et al. Mesenchymal stem-cell transplantation for hypoxic-ischemic brain injury in neonatal rat model. Pediatr Res. 2009;67(1):42–6. https://doi.org/10.1203/PDR.0b013e3181bf594b.

    Article  Google Scholar 

  20. van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ. Nasal administration of stem cells: a promising novel route to treat neonatal ischemic brain damage. Pediatr Res. 2010b;68(5):419–22. https://doi.org/10.1203/PDR.0b013e3181f1c289.

    PubMed  Google Scholar 

  21. Danielyan L, Schafer R, von Ameln-Mayerhofer A, Buadze M, Geisler J, Klopfer T, et al. Intranasal delivery of cells to the brain. Eur J Cell Biol. 2009;88(6):315–24. https://doi.org/10.1016/j.ejcb.2009.02.001.

    Article  CAS  PubMed  Google Scholar 

  22. Donega V, van Velthoven CT, Nijboer CH, van Bel F, Kas MJ, Kavelaars A, et al. Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement. PLoS One. 2013;8(1):e51253. https://doi.org/10.1371/journal.pone.0051253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Donega V, Nijboer CH, van Tilborg G, Dijkhuizen RM, Kavelaars A, Heijnen CJ. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury. Exp Neurol. 2014b;261:53–64. https://doi.org/10.1016/j.expneurol.2014.06.009.

    Article  CAS  PubMed  Google Scholar 

  24. Donega V, Nijboer CH, van Velthoven CT, Youssef SA, de Bruin A, van Bel F, et al. Assessment of long-term safety and efficacy of intranasal mesenchymal stem cell treatment for neonatal brain injury in the mouse. Pediatr Res. 2015;78(5):520–6. https://doi.org/10.1038/pr.2015.145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Park WS, Sung SI, Ahn SY, Yoo HS, Sung DK, Im GH, et al. Hypothermia augments neuroprotective activity of mesenchymal stem cells for neonatal hypoxic-ischemic encephalopathy. PLoS One. 2015;10(3):e0120893. https://doi.org/10.1371/journal.pone.0120893.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ahn SY, Chang YS, Sung DK, Sung SI, Yoo HS, Lee JH, et al. Mesenchymal stem cells prevent hydrocephalus after severe intraventricular hemorrhage. Stroke. 2013;44(2):497–504. https://doi.org/10.1161/strokeaha.112.679092.

    Article  CAS  PubMed  Google Scholar 

  27. Ahn SY, Chang YS, Sung DK, Sung SI, Yoo HS, Im GH, et al. Optimal route for mesenchymal stem cells transplantation after severe intraventricular hemorrhage in newborn rats. PLoS One. 2015;10(7):e0132919. https://doi.org/10.1371/journal.pone.0132919.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bunnell BA, Flaat M, Gagliardi C, Patel B, Ripoll C. Adipose-derived stem cells: isolation, expansion and differentiation. Methods. 2008;45(2):115–20. https://doi.org/10.1016/j.ymeth.2008.03.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gimble J, Guilak F. Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy. 2003;5(5):362–9. https://doi.org/10.1080/14653240310003026.

    Article  PubMed  Google Scholar 

  30. Park D, Lee SH, Bae DK, Yang YH, Yang G, Kyung J, et al. Transplantation of human adipose tissue-derived Mesenchymal stem cells restores the neurobehavioral disorders of rats with neonatal hypoxic-ischemic encephalopathy. Cell Med. 2013;5(1):17–28. https://doi.org/10.3727/215517913x658936.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sugihara H, Yonemitsu N, Miyabara S, Yun K. Primary cultures of unilocular fat cells: characteristics of growth in vitro and changes in differentiation properties. Differentiation. 1986;31(1):42–9.

    Article  CAS  PubMed  Google Scholar 

  32. Matsumoto T, Kano K, Kondo D, Fukuda N, Iribe Y, Tanaka N, et al. Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage potential. J Cell Physiol. 2008;215(1):210–22. https://doi.org/10.1002/jcp.21304.

    Article  CAS  PubMed  Google Scholar 

  33. Yagi K, Kondo D, Okazaki Y, Kano K. A novel preadipocyte cell line established from mouse adult mature adipocytes. Biochem Biophys Res Commun. 2004;321(4):967–74. https://doi.org/10.1016/j.bbrc.2004.07.055.

    Article  CAS  PubMed  Google Scholar 

  34. Shen JF, Sugawara A, Yamashita J, Ogura H, Sato S. Dedifferentiated fat cells: an alternative source of adult multipotent cells from the adipose tissues. Int J Oral Sci. 2011;3(3):117–24. https://doi.org/10.4248/IJOS11044.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Yamagata M, Yamamoto A, Kako E, Kaneko N, Matsubara K, Sakai K, et al. Human dental pulp-derived stem cells protect against hypoxic-ischemic brain injury in neonatal mice. Stroke. 2013;44(2):551–4. https://doi.org/10.1161/STROKEAHA.112.676759.

    Article  PubMed  Google Scholar 

  36. Fang CZ, Yang YJ, Wang QH, Yao Y, Zhang XY, He XH. Intraventricular injection of human dental pulp stem cells improves hypoxic-ischemic brain damage in neonatal rats. PLoS One. 2013;8(6):e66748. https://doi.org/10.1371/journal.pone.0066748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan

    Yoshiaki Sato M.D., Ph.D.

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  1. Yoshiaki Sato M.D., Ph.D.
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Correspondence to Yoshiaki Sato M.D., Ph.D. .

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Editors and Affiliations

  1. Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan

    Haruo Shintaku

  2. Department of Pediatrics, University of Tokyo, Tokyo, Japan

    Akira Oka

  3. Department of Pediatrics, Yodogawa Christian Hospital, Osaka, Japan

    Makoto Nabetani

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Sato, Y. (2018). Other Tissues-Derived Mesenchymal Stem Cells for Perinatal Brain Injury. In: Shintaku, H., Oka, A., Nabetani, M. (eds) Cell Therapy for Perinatal Brain Injury. Springer, Singapore. https://doi.org/10.1007/978-981-10-1412-3_7

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  • DOI: https://doi.org/10.1007/978-981-10-1412-3_7

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  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-1411-6

  • Online ISBN: 978-981-10-1412-3

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