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The Effects of Umbilical Cord Blood and Cord Tissue Cell Therapies in Animal and Human Models of Cerebral Palsy

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Cerebral Palsy

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Abstract

Biologic and cell-based therapies are increasingly being developed for a multitude of diseases. They are being explored in the treatment of neurologic conditions, as traditional pharmacologic agents typically cannot fully address the pathologic complexity and resultant manifestations of injuries and diseases affecting the brain. Umbilical cord blood and cord tissue are attractive sources of cells for these therapies as they are readily available and easily obtained without risk to the donor infant or mother and because they can be routinely screened and banked. This chapter will describe the current state of investigations of umbilical cord blood and cord tissue-based therapies in the treatment of cerebral palsy due to an acquired brain injury and highlight some of the possibilities and challenges inherent in develo** and assessing such therapies in this population.

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References

  • Ahn SY, Chang YS, Sung DK, Sung SI, Yoo HS, Lee JH, Oh WI, Park WS (2013) Mesenchymal stem cells prevent hydrocephalus after severe intraventricular hemorrhage. Stroke 44:497–504

    Article  CAS  Google Scholar 

  • Archambault J, Moreira A, McDaniel D, Winter L, Sun L, Hornsby P (2017) Therapeutic potential of mesenchymal stromal cells for hypoxic ischemic encephalopathy: A systematic review and meta-analysis of preclinical studies. PLoS One 12:e0189895

    Article  Google Scholar 

  • Aridas JD, McDonald CA, Paton MC, Yawno T, Sutherland AE, Nitsos I, Pham Y, Ditchfield M, Fahey MC, Wong F, Malhotra A, Castillo-Melendez M, Bhakoo K, Wallace EM, Jenkin G, Miller SL (2016) Cord blood mononuclear cells prevent neuronal apoptosis in response to perinatal asphyxia in the newborn lamb. J Physiol 594:1421–1435

    Article  CAS  Google Scholar 

  • Arien-Zakay H, Lecht S, Bercu MM, Tabakman R, Kohen R, Galski H, Nagler A, Lazarovici P (2009) Neuroprotection by cord blood neural progenitors involves antioxidants, neurotrophic and angiogenic factors. Exp Neurol 216:83–94

    Article  CAS  Google Scholar 

  • Bliss T, Guzman R, Daadi M, Steinberg GK (2007) Cell transplantation therapy for stroke. Stroke 38:817–826

    Article  Google Scholar 

  • Borlongan CV, Hadman M, Sanberg CD, Sanberg PR (2004) Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke. Stroke 35:2385–2389

    Article  Google Scholar 

  • Carmichael ST (2003) Plasticity of cortical projections after stroke. Neuroscientist 9:64–75

    Article  Google Scholar 

  • Carr LJ, Harrison LM, Evans AL, Stephens JA (1993) Patterns of central motor reorganization in hemiplegic cerebral palsy. Brain 116. (Pt 5:1223–1247

    Article  Google Scholar 

  • Castillo-Melendez M, Yawno T, Jenkin G, Miller SL (2013) Stem cell therapy to protect and repair the develo** brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells. Front Neurosci 7:194

    Article  Google Scholar 

  • Chen J, Sanberg PR, Li Y, Wang L, Lu M, Willing AE, Sanchez-Ramos J, Chopp M (2001) Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke 32:2682–2688

    Article  CAS  Google Scholar 

  • Chen J, Zhang ZG, Li Y, Wang L, Xu YX, Gautam SC, Lu M, Zhu Z, Chopp M (2003) Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res 92:692–699

    Article  CAS  Google Scholar 

  • Chen J, Venkat P, Zacharek A, Chopp M (2014) Neurorestorative therapy for stroke. Front Hum Neurosci 8:382

    PubMed  PubMed Central  Google Scholar 

  • Cotten CM, Murtha AP, Goldberg RN, Grotegut CA, Smith PB, Goldstein RF, Fisher KA, Gustafson KE, Waters-Pick B, Swamy GK, Rattray B, Tan S, Kurtzberg J (2014) Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. J Pediatr 164(5):973–979

    Article  Google Scholar 

  • Derrick M, Drobyshevsky A, Ji X, Tan S (2007) A model of cerebral palsy from fetal hypoxia-ischemia. Stroke 38:731–735

    Article  Google Scholar 

  • Donega V, Van Velthoven CT, Nijboer CH, Van Bel F, Kas MJ, Kavelaars A, Heijnen CJ (2013) Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement. PLoS One 8:e51253

    Article  CAS  Google Scholar 

  • Drobyshevsky A, Cotten CM, Shi Z, Luo K, Jiang R, Derrick M, Tracy ET, Gentry T, Goldberg RN, Kurtzberg J, Tan S (2015) Human umbilical cord blood cells ameliorate motor deficits in rabbits in a cerebral palsy model. Dev Neurosci 37:349–362

    Article  CAS  Google Scholar 

  • Englander ZA, Sun J, Laura C, Mikati MA, Kurtzberg J, Song AW (2015) Brain structural connectivity increases concurrent with functional improvement: evidence from diffusion tensor MRI in children with cerebral palsy during therapy. Neuroimage Clin 7:315–324

    Article  Google Scholar 

  • Guzzetta A, Bonanni P, Biagi L, Tosetti M, Montanaro D, Guerrini R, Cioni G (2007) Reorganisation of the somatosensory system after early brain damage. Clin Neurophysiol 118:1110–1121

    Article  CAS  Google Scholar 

  • Hanna SE, Bartlett DJ, Rivard LM, Russell DJ (2008) Reference curves for the gross motor function measure: percentiles for clinical description and tracking over time among children with cerebral palsy. Phys Ther 88:596–607

    Article  Google Scholar 

  • Huang L, Zhang C, Gu J, Wu W, Shen Z, Zhou X, Lu H (2018) A randomized, placebo-controlled trial of human umbilical cord blood mesenchymal stem cell infusion for children with cerebral palsy. Cell Transplant 27:325–334

    Article  Google Scholar 

  • Kang M, Min K, Jang J, Kim SC, Kang MS, Jang SJ, Lee JY, Kim SH, Kim MK, An SA, Kim M (2015) Involvement of immune responses in the efficacy of cord blood cell therapy for cerebral palsy. Stem Cells Dev 24:2259–2268

    Article  CAS  Google Scholar 

  • Kim ES, Ahn SY, Im GH, Sung DK, Park YR, Choi SH, Choi SJ, Chang YS, Oh W, Lee JH, Park WS (2012) Human umbilical cord blood-derived mesenchymal stem cell transplantation attenuates severe brain injury by permanent middle cerebral artery occlusion in newborn rats. Pediatr Res 72:277–284

    Article  CAS  Google Scholar 

  • Lei J, Firdaus W, Rosenzweig JM, Alrebh S, Bakhshwin A, Borbiev T, Fatemi A, Blakemore K, Johnston MV, Burd I (2015) Murine model: maternal administration of stem cells for prevention of prematurity. Am J Obstet Gynecol 212:639 e1–639. e10

    Article  Google Scholar 

  • Lin YC, Ko TL, Shih YH, Lin MY, Fu TW, Hsiao HS, Hsu JY, Fu YS (2011) Human umbilical mesenchymal stem cells promote recovery after ischemic stroke. Stroke 42:2045–2053

    Article  Google Scholar 

  • Llado J, Haenggeli C, Maragakis NJ, Snyder EY, Rothstein JD (2004) Neural stem cells protect against glutamate-induced excitotoxicity and promote survival of injured motor neurons through the secretion of neurotrophic factors. Mol Cell Neurosci 27:322–331

    Article  CAS  Google Scholar 

  • Meier C, Middelanis J, Wasielewski B, Neuhoff S, Roth-Haerer A, Gantert M, Dinse HR, Dermietzel R, Jensen A (2006) Spastic paresis after perinatal brain damage in rats is reduced by human cord blood mononuclear cells. Pediatr Res 59:244–249

    Article  Google Scholar 

  • Min K, Song J, Kang JY, Ko J, Ryu JS, Kang MS, Jang SJ, Kim SH, Oh D, Kim MK, Kim SS, Kim M (2013) Umbilical cord blood therapy potentiated with erythropoietin for children with cerebral palsy: a double-blind, randomized, placebo-controlled trial. Stem Cells 31:581–591

    Article  CAS  Google Scholar 

  • Mukai T, Mori Y, Shimazu T, Takahashi A, Tsunoda H, Yamaguchi S, Kiryu S, Tojo A, Nagamura-Inoue T (2017) Intravenous injection of umbilical cord-derived mesenchymal stromal cells attenuates reactive gliosis and hypomyelination in a neonatal intraventricular hemorrhage model. Neuroscience 355:175–187

    Article  CAS  Google Scholar 

  • Nan Z, Grande A, Sanberg CD, Sanberg PR, Low WC (2005) Infusion of human umbilical cord blood ameliorates neurologic deficits in rats with hemorrhagic brain injury. Ann N Y Acad Sci 1049:84–96

    Article  Google Scholar 

  • Park WS, Sung SI, Ahn SY, Sung DK, Im GH, Yoo HS, Choi SJ, Chang YS (2016) Optimal timing of mesenchymal stem cell therapy for neonatal intraventricular hemorrhage. Cell Transplant 25:1131–1144

    Article  Google Scholar 

  • Romanov YA, Tarakanov OP, Radaev SM, Dugina TN, Ryaskina SS, Darevskaya AN, Morozova YV, Khachatryan WA, Lebedev KE, Zotova NS, Burkova AS, Sukhikh GT, Smirnov VN (2015) Human allogeneic AB0/Rh-identical umbilical cord blood cells in the treatment of juvenile patients with cerebral palsy. Cytotherapy 17(7):969–978

    Article  Google Scholar 

  • Rosenbaum PL, Walter SD, Hanna SE, Palisano RJ, Russell DJ, Raina P, Wood E, Bartlett DJ, Galuppi BE (2002) Prognosis for gross motor function in cerebral palsy: creation of motor development curves. JAMA 288:1357–1363

    Article  Google Scholar 

  • Shen LH, Li Y, Chen J, Zacharek A, Gao Q, Kapke A, Lu M, Raginski K, Vanguri P, Smith A, Chopp M (2007) Therapeutic benefit of bone marrow stromal cells administered 1 month after stroke. J Cereb Blood Flow Metab 27:6–13

    Article  Google Scholar 

  • Staudt M, Grodd W, Gerloff C, Erb M, Stitz J, Krageloh-Mann I (2002) Two types of ipsilateral reorganization in congenital hemiparesis: a TMS and fMRI study. Brain 125:2222–2237

    Article  Google Scholar 

  • Sun J, Allison J, McLaughlin C, Sledge L, Waters-Pick B, Wease S, Kurtzberg J (2010) Differences in quality between privately and publicly banked umbilical cord blood units: a pilot study of autologous cord blood infusion in children with acquired neurologic disorders. Transfusion 50:1980–1987

    Article  Google Scholar 

  • Sun J, Mikati M, Troy J, McLaughlin C, Jasien J, Case L, Worley G, Kurtzberg J (2017a) Sibling umbilical cord blood infusion is safe in children with cerebral palsy. Dev Med Child Neurol 59:115

    Google Scholar 

  • Sun JM, Song AW, Case LE, Mikati MA, Gustafson KE, Simmons R, Goldstein R, Petry J, McLaughlin C, Waters-Pick B, Chen LW, Wease S, Blackwell B, Worley G, Troy J, Kurtzberg J (2017b) Effect of autologous cord blood infusion on motor function and brain connectivity in young children with cerebral palsy: a randomized, placebo-controlled trial. Stem Cells Transl Med 6:2071–2078

    Article  CAS  Google Scholar 

  • Sutcliffe TL, Gaetz WC, Logan WJ, Cheyne DO, Fehlings DL (2007) Cortical reorganization after modified constraint-induced movement therapy in pediatric hemiplegic cerebral palsy. J Child Neurol 22:1281–1287

    Article  Google Scholar 

  • Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, Tsukamoto Y, Iso H, Fujimori Y, Stern DM, Naritomi H, Matsuyama T (2004) Administration of Cd34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest 114:330–338

    Article  CAS  Google Scholar 

  • Tanaka E, Ogawa Y, Mukai T, Sato Y, Hamazaki T, Nagamura-Inoue T, Harada-Shiba M, Shintaku H, Tsuji M (2018) Dose-dependent effect of intravenous administration of human umbilical cord-derived mesenchymal stem cells in neonatal stroke mice. Front Neurol 9:133

    Article  Google Scholar 

  • Van Velthoven CT, Kavelaars A, Van Bel F, Heijnen CJ (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 

  • Vendrame M, Cassady J, Newcomb J, Butler T, Pennypacker KR, Zigova T, Sanberg CD, Sanberg PR, Willing AE (2004) Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral deficits and reduces infarct volume. Stroke 35:2390–2395

    Article  Google Scholar 

  • Vendrame M, Gemma C, De Mesquita D, Collier L, Bickford PC, Sanberg CD, Sanberg PR, Pennypacker KR, Willing AE (2005) Anti-inflammatory effects of human cord blood cells in a rat model of stroke. Stem Cells Dev 14:595–604

    Article  CAS  Google Scholar 

  • Wagenaar N, Nijboer CH, Van Bel F (2017) Repair of neonatal brain injury: bringing stem cell-based therapy into clinical practice. Dev Med Child Neurol 59:997–1003

    Article  Google Scholar 

  • Wang L, Ji H, Zhou J, **e J, Zhong Z, Li M, Bai W, Li N, Zhang Z, Wang X, Zhu D, Liu Y, Wu M (2013a) Therapeutic potential of umbilical cord mesenchymal stromal cells transplantation for cerebral palsy: a case report. Case Rep Transplant 2013:146347

    PubMed  PubMed Central  Google Scholar 

  • Wang X, Cheng H, Hua R, Yang J, Dai G, Zhang Z, Wang R, Qin C, An Y (2013b) Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: a preliminary clinical study. Cytotherapy 15:1549–1562

    Article  Google Scholar 

  • Wang X, Hu H, Hua R, Yang J, Zheng P, Niu X, Cheng H, Dai G, Liu X, Zhang Z, An Y (2015) Effect of umbilical cord mesenchymal stromal cells on motor functions of identical twins with cerebral palsy: pilot study on the correlation of efficacy and hereditary factors. Cytotherapy 17:224–231

    Article  Google Scholar 

  • Willing AE, Lixian J, Milliken M, Poulos S, Zigova T, Song S, Hart C, Sanchez-Ramos J, Sanberg PR (2003) Intravenous versus intrastriatal cord blood administration in a rodent model of stroke. J Neurosci Res 73:296–307

    Article  CAS  Google Scholar 

  • Wood E, Rosenbaum P (2000) The gross motor function classification system for cerebral palsy: a study of reliability and stability over time. Dev Med Child Neurol 42:292–296

    Article  CAS  Google Scholar 

  • Yang B, Migliati E, Parsha K, Schaar K, ** X, Aronowski J, Savitz SI (2013) Intra-arterial delivery is not superior to intravenous delivery of autologous bone marrow mononuclear cells in acute ischemic stroke. Stroke 44:3463–3472

    Article  CAS  Google Scholar 

  • You SH, Jang SH, Kim YH, Kwon YH, Barrow I, Hallett M (2005) Cortical reorganization induced by virtual reality therapy in a child with hemiparetic cerebral palsy. Dev Med Child Neurol 47:628–635

    Article  Google Scholar 

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Authors and Affiliations

  1. Marcus Center for Cellular Cures, Robertson Clinical and Translational Cell Therapy Program, Duke University Medical Center, Durham, NC, USA

    Jessica M. Sun & Joanne Kurtzberg

Authors
  1. Jessica M. Sun
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  2. Joanne Kurtzberg
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Corresponding author

Correspondence to Jessica M. Sun .

Editor information

Editors and Affiliations

  1. Alfred I. duPont Institute, Wilmington, DE, USA

    Freeman Miller

  2. Cerebral Palsy Program, AI DuPont Hospital for Children , Wilmington, DE, USA

    Steven Bachrach

  3. AI DuPont Hospital for Children , Wilmington, DE, USA

    Nancy Lennon

  4. Drexel University, PHILADELPHIA, PA, USA

    Margaret O'Neil

Section Editor information

  1. Department of Pediatrics (Emeritus), Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA

    Steven J. Bachrach

  2. Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA

    Steven J. Bachrach

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Sun, J.M., Kurtzberg, J. (2019). The Effects of Umbilical Cord Blood and Cord Tissue Cell Therapies in Animal and Human Models of Cerebral Palsy. In: Miller, F., Bachrach, S., Lennon, N., O'Neil, M. (eds) Cerebral Palsy. Springer, Cham. https://doi.org/10.1007/978-3-319-50592-3_223-1

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  • DOI: https://doi.org/10.1007/978-3-319-50592-3_223-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-50592-3

  • Online ISBN: 978-3-319-50592-3

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