Stem Cell Reviews and Reports

, Volume 15, Issue 5, pp 717–729 | Cite as

A Retrospective Analysis of Safety and Efficacy of Wharton’s Jelly Stem Cell Administration in Children with Spina Bifida

  • Dariusz BoruczkowskiEmail author
  • Izabela Zdolińska-Malinowska
Original Article


The aim of this paper was to describe the outcome of therapeutic administration of mesenchymal stem cells (MSC) obtained from Wharton’s jelly (WJ-MSCs) in paediatric patients with spina bifida (SB) during a medical therapeutic experiment. We retrospectively analysed the records of twenty-eight patients aged 1–18 years (median age 4 years) recruited in daily clinical practice. Each patient received 0.9–5.0 × 106 WJ-MSCs/kg (median 2.6 × 106 WJ-MSCs/kg) administered in 1–5 injections as an experimental treatment for SB (allogenic administration). All the patients were examined by the same neurologist (study investigator, SI) on the day of each infusion. Based on the neurological examination, the SI used a six-point Likert scale to assess the quality of life and self-service of each patient. Twenty-six follow-up observations after MSC administration were analysed retrospectively. In addition, the assessments of the parents and other healthcare professionals were obtained for 5 patients and compared with the SI’s assessment. Twenty-one of 26 patients (81%) experienced some improvement in their health status. Twenty-one (81%) patients experienced increased quality of life (median 2.0) and 10 patients (38%) achieved a slight increase in their self-service level (median 1). Improvement was achieved in 12 out of 17 areas. Five were significant in low-power sign test: muscle tension, muscle strength, gross motor development, micturition/defecation control, and cognitive functions. Adverse events were mild and temporary. Age, body mass, single dose or poor response after the first administration were not significant predictors of later response to treatment in contrast to the total cell dose per one kg in the whole treatment course. WJ-MSC administration is a safe and effective procedure that improves motor functions, micturition/defecation control, and cognitive functions, and improves the quality of life in children with SB.


Spina bifida Myelomeningocele Stem cell Therapy Treatment MSC Mesenchymal stem cells Congenital spinal malformations 



The authors would like to thank Magdalena Chrościńska-Krawczyk from the Department of Paediatric Neurology, Lublin Medical University, Lublin, Poland, for the qualification of patients, supervision during the therapy and medical examination during follow-ups. They also wish to thank Tomasz Ołdak from the Laboratory at Polski Bank Komórek Macierzystych S.A. (FamiCord Group), Warsaw, Poland, for his supervision during the preparation of Wharton’s jelly-derived mesenchymal stem cells. The collection of biological material was carried out as part of the commercial services provided by Polski Bank Komórek Macierzystych S.A., with the participation of medical staff from public hospitals and employees of Polski Bank Komórek Macierzystych S.A. Language assistance was provided by Marisa Granados.


The study was sponsored by Polski Bank Komórek Macierzystych S.A. (FamiCord Group), Warsaw, Poland.

Compliance with Ethical Standards

Conflict of Interest

Both authors are employees of Polski Bank Komórek Macierzystych S.A. (FamiCord Group), Warsaw, Poland.


  1. 1.
    Mulinare, J., Cordero, J. F., Erickson, J. D., & Berry, R. J. (1988). Periconceptional use of multivitamins and the occurrence of neural tube defects. JAMA, 260(21), 3141–3145.PubMedGoogle Scholar
  2. 2.
    Atta, C. A. M., Fiest, K. M., Frolkis, A. D., Jette, N., Pringsheim, T., St Germaine-Smith, C., et al. (2016). Global birth prevalence of spina bifida by folic acid fortification status: A systematic review and meta-analysis. American Journal of Public Health, 106(1), e24–e34.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Zieba, J., Miller, A., Gordiienko, O., Smith, G. M., & Krynska, B. (2017). Clusters of amniotic fluid cells and their associated early neuroepithelial markers in experimental myelomeningocele: Correlation with astrogliosis. PLoS One, 12(3), e0174625.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Marotta, M., Fernández-Martín, A., Oria, M., Fontecha, C. G., Giné, C., Martínez-Ibáñez, V., et al. (2017). Isolation, characterization, and differentiation of multipotent neural progenitor cells from human cerebrospinal fluid in fetal cystic myelomeningocele. Stem Cell Research, 22, 33–42.PubMedGoogle Scholar
  5. 5.
    Baraniak, P. R., & McDevitt, T. C. (2010). Stem cell paracrine actions and tissue regeneration. Regenerative Medicine, 5, 121–143.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Jiao, Y., Li, X., & Liu, J. (2018). A new approach to cerebral palsy treatment: Discussion of the effective components of umbilical cord blood and its mechanisms of action. Cell Transplantation, 1, 096368971880965. Scholar
  7. 7.
    Riazifar, M., Mohammadi, M. R., Pone, E. J., Yeri, A., Lässer, C., Segaliny, A. I., et al. (2019). Stem cell-derived exosomes as Nanotherapeutics for autoimmune and neurodegenerative disorders. ACS Nano. 2019 may 29.
  8. 8.
    Drommelschmidt, K., Serdar, M., Bendix, I., Herz, J., Bertling, F., Prager, S., et al. (2017). Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury. Brain Beh. Immun., 60, 220–232.Google Scholar
  9. 9.
    Kim, D., Nishida, H., An, S. Y., Shetty, A. K., Bartosh, T. J., & Prockop, D. J. (2016). Chromatographically isolated CD63+ CD81+ extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI. Proceedings of the National Academy of Sciences of the United States of America, 113, 170–175.PubMedGoogle Scholar
  10. 10.
    Xin, H., Katakowski, M., Wang, F., Yang, J. J., Zhang, Z. G., & Chopp, M. (2013). Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J. Cer. Blood Flow Met., 33, 1711–1715.Google Scholar
  11. 11.
    Jarmalaviciute, A., Tunaitis, V., Pivoraite, U., Venalis, A., & Pivoriunas, A. (2015). Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine–induced apoptosis. Cytotherapy, 17, 932–939.PubMedGoogle Scholar
  12. 12.
    Katsuda, T., Tsuchiya, R., Kosaka, N., Yoshioka, Y., Takagaki, K., Oki, K., et al. (2013). Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes. Scientific Reports, 3, 1197.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Perets, N., Hertz, S., London, M., & Oen, D. (2018). Intranasal administration of exosomes derived from mesenchymal stem cells ameliorates autistic-like behaviors of BTBR mice. Mol. Autism, 9, 57.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Osier, N., Motamedi, V., Edwards, K., Puccio, A., Diaz-Arrastia, R., Kenney, K., & Gill, J. (2018). Exosomes in acquired neurological disorders: New insights into pathophysiology and treatment. Molecular Neurobiology, 55, 9280–9293.PubMedGoogle Scholar
  15. 15.
    Kordelas, L., Rebmann, V., Ludwig, A.-K., Radtke, S., Ruesing, J., Doeppner, T. R., et al. (2014). MSC-derived exosomes: A novel tool to treat therapy-refractory graft-versus-host disease. Leukemia, 28, 970–973.PubMedGoogle Scholar
  16. 16.
    Nassar, W., El-Ansary, M., Sabry, D., Mostafa, M. A., Fayad, T., Kotb, E., et al. (2016). Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater. Res., 20, 21.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Wiklander, O. P. B., Brennan, M. Á., Lötvall, J., Breakefield, X. O., & El Andaloussi, S. (2019). Advances in therapeutic applications of extracellular vesicles. Sci Transl Med, 11(492).Google Scholar
  18. 18.
    Sharma, A. K., Bury, M. I., Fuller, N. J., Marks, A. J., Kollhoff, D. M., Rao, M. V., et al. (2013). Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration. Proceedings of National Acadademy of Sciences USA, 110(10), 4003–4008.Google Scholar
  19. 19.
    Sahoo, S., Klychko, E., Thorne, T., Misener, S., Schultz, K. M., Millay, M., et al. (2011). Exosomes from human CD34+ stem cells mediate their proangiogenic paracrine activity. Circulation Research, 109(7), 724–728.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Losordo, D. W., Henry, T. D., Davidson, C., Sup Lee, J., Costa, M. A., Bass, T., et al. (2011). Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circulation Research, 109(4), 428–436.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Steidl, U., Bork, S., Schaub, S., Selbach, O., Seres, J., Aivado, M., et al. (2004). Primary human CD34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators. Blood, 104(1), 81–88.PubMedGoogle Scholar
  22. 22.
    Li, X., Yuan, Z., Wei, X., Li, H., Zhao, G., Miao, J., et al. (2016). Application potential of bone marrow mesenchymal stem cell (BMSCs) based tissue-engineering for spinal cord defect repair in rat fetuses with spina bifida aperta. The Journal of Materials Science: Materials in Medicine, 27(4), 77.Google Scholar
  23. 23.
    Joseph, D. B., Borer, J. G., De Filippo, R. E., Hodges, S. J., & McLorie, G. A. (2014). Autologous cell seeded biodegradable scaffold for augmentation Cystoplasty: Phase II study in children and adolescents with spina bifida. The Journal of Urology, 191(5), 1389–1395.PubMedGoogle Scholar
  24. 24.
    Donders, R., Bogie, J. F. J., Ravanidis, S., Gervois, P., Vanheusden, M., Marée, R., et al. (2018). Human Wharton's jelly-derived stem cells display a distinct immunomodulatory and Proregenerative transcriptional signature compared to bone marrow-derived stem cells. Stem Cells and Development, Jan 15, 27(2), 65–84.Google Scholar
  25. 25.
    Weiss, M., Medicetty, S., Bledsoe, A. R., Rachakatla, R. S., Choi, M., Merchav, S., et al. (2006). Human umbilical cord matrix stem cells: Preliminary characterization and effect of transplantation in a rodent model of Parkinson disease. Stem Cells, 24, 781–792.PubMedGoogle Scholar
  26. 26.
    Mitchell, K. E., Weiss, M. L., Mitchell, B. M., Martin, P., Davis, D., Morales, L., et al. (2003). Matrix cells from Wharton’s jelly form neurons and glia. Stem Cells, 21, 50–60.Google Scholar
  27. 27.
    Boruczkowski, D., & Zdolińska-Malinowska, I. (2019). Wharton’s jelly mesenchymal stem cell administration improves quality of life and self-sufficiency in children with cerebral palsy: Results from a retrospective study. Stem Cells International ID: 7402151.Google Scholar
  28. 28.
    Muraglia, A., Cancedda, R., & Quarto, R. (2000). Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. Journal of Cell Science, 113(7), 1161–1166.PubMedGoogle Scholar
  29. 29.
    Galdersi, U., & Giordano, A. (2014). The gap between the physiological and therapeutic roles of mesenchymal stem cells. Medicinal Research Reviews, 34(5), 1100–1126.Google Scholar
  30. 30.
    Squillaro, T., Peluso, G., & Galdersi, U. (2016). Clinical trials with mesenchymal stem cells: an update. Cell Transplantation, 25(5), 829–848.PubMedGoogle Scholar
  31. 31.
    Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., et al. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8(4), 315–317.PubMedGoogle Scholar
  32. 32.
    Wang, Q., Yang, Q., Wang, Z., Tong, H., Ma, L., Zhang, Y., et al. (2016). Comparative analysis of human mesenchymal stem cells from fetal-bone marrow, adipose tissue, and Warton's jelly as sources of cell immunomodulatory therapy. Human Vaccines & Immunotherapeutics, 12(1), 85–96.Google Scholar
  33. 33.
    Drela, K., Lech, W., Figiel-Dabrowska, A., Zychowicz, M., Mikula, M., Sarnowska, A., et al. (2016). Enhanced neuro-therapeutic potential of Wharton's jelly-derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture. Cytotherapy, 18(4), 497–509.PubMedGoogle Scholar
  34. 34.
    Hsieh, J. Y., Wang, H. W., Chang, S. J., Liao, K. H., Lee, I. H., Lin, W. S., et al. (2013). Mesenchymal stem cells from human umbilical cord express preferentially secreted factors related to neuroprotection, neurogenesis, and angiogenesis. PLoS One, 8(8), e72604.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Munir, H., Luu, N.-T., Clarke, L. S. C., Nash, G. B., & McGettrick, H. M. (2016). Comparative ability of mesenchymal stromal cells from different tissues to limit neutrophil recruitment to inflamed endothelium. PLoS One, 11(5), e0155161.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Iannaccone, P. M., Galat, V., Bury, M. I., Ma, Y. C., & Sharma, A. K. (2018). The utility of stem cells in pediatric urinary bladder regeneration. Pediatric Research, 83, 258–266.PubMedGoogle Scholar
  37. 37.
    Sharma, A. K., Fuller, N. J., Sullivan, R. R., Fulton, N., Hota, P. V., Harrington, D. A., et al. (2009). Defined populations of bone marrow derived mesenchymal stem and endothelial progenitor cells for bladder regeneration. Journal of Urology, 182(4), 1898–1905.PubMedGoogle Scholar
  38. 38.
    Sharma, A. K., Hota, P. V., Matoka, D. J., Fuller, N. J., Jandali, D., Thaker, H., et al. (2010). Urinary bladder smooth muscle regeneration utilizing bone marrow derived mesenchymal stem cell seeded elastomeric poly(1,8-octanediol-co-citrate) based thin films. Biomaterials, 31(24), 6207–6217.PubMedGoogle Scholar
  39. 39.
    Ferrari, G. (1998). Muscle regeneration by bone marrow-derived myogenic progenitors. Science, 279(5356), 1528–1530.PubMedGoogle Scholar
  40. 40.
    Mafi, R. (2001). Sources of adult mesenchymal stem cells applicable for musculoskeletal applications - a systematic review of the literature. The Open Orthopaedics Journal, 5(1), 242–248.Google Scholar
  41. 41.
    Sharma, A., Sane, H., Badhe, P., Gokulchandran, N., Kulkarni, P., Lohiya, M., et al. (2013). A clinical study shows safety and efficacy of autologous bone marrow mononuclear cell therapy to improve quality of life in muscular dystrophy patients. Cell Transplantation, 22(1_suppl), 127–138.Google Scholar
  42. 42.
    Li, P., Cui, K. A. I., Zhang, B. O., Wang, Z., Shen, Y., Wang, X., et al. (2015). Transplantation of human umbilical cord-derived mesenchymal stems cells for the treatment of Becker muscular dystrophy in affected pedigree members. International Journal of Molecular Medicine, 35(4), 1051–1057.PubMedGoogle Scholar
  43. 43.
    Sharma, A., Gokulchandran, N., Chopra, G., Kulkarni, P., Lohia, M., Badhe, P., et al. (2012). Administration of Autologous Bone Marrow-Derived Mononuclear Cells in children with incurable neurological disorders and injury is safe and improves their quality of life. Cell Transplantation, 21(1), S79–S90.PubMedGoogle Scholar
  44. 44.
    Liem, N. T., Chinh, V. D., Thinh, N. T., Minh, N. D., & Duc, H. M. (2018). Improved bowel function in patients with spina bifida after bone marrow-derived mononuclear cell transplantation: A report of 2 cases. American Journal of Case Reports, 19, 1010–1018.PubMedGoogle Scholar
  45. 45.
    Salehi-Pourmehr, H., Rahbarghazi, R., Mahmoudi, J., Roshangar, L., Chapple, C. R., Hajebrahimi, S., et al. (2019). Intra-bladder wall transplantation of bone marrow mesenchymal stem cells improved urinary bladder dysfunction following spinal cord injury. Life Sciences, 221, 20–28.Google Scholar
  46. 46.
    Shandley, S., Wolf, E. G., Schubert-Kappan, C. M., Baugh, L. M., Richards, M. F., Prye, J., et al. (2017). Increased circulating stem cells and better cognitive performance in traumatic brain injury subjects following hyperbaric oxygen therapy. Undersea and Hyperbaric Medicine, 44(3), 257–269.PubMedGoogle Scholar
  47. 47.
    Acharya, M. M., Martirosian, V., Chmielewski, N. N., Hanna, N., Tran, K. K., Liao, A. C., et al. (2015). Stem cell transplantation reverses chemotherapy-induced cognitive dysfunction. Cancer Research, 75(4), 676–686.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Acharya, M. M., Christie, L.-A., Hazel, T. G., Johe, K. K., & Limoli, C. L. (2014). Transplantation of human fetal-derived neural stem cells improves cognitive function following cranial irradiation. Cell Transplantation, 23(10), 1255–1266.PubMedGoogle Scholar
  49. 49.
    Ozdemir, M., Attar, A., Kuzu, I., Ayten, M., Ozgencil, E., Bozkurt, M., et al. (2012). Stem cell therapy in spinal cord injury: In vivo and postmortem tracking of bone marrow mononuclear or mesenchymal stem cells. Stem Cell Reviews and Reports, 8(3), 953–962.Google Scholar
  50. 50.
    Mishra, S. K., Khushu, S., Singh, A. K., & Gangenahalli, G. (2018). Homing and tracking of Iron oxide labelled mesenchymal stem cells after infusion in traumatic brain injury mice: A longitudinal in vivo MRI study. Stem Cell Reviews and Reports, Dec, 14(6), 888–900.Google Scholar
  51. 51.
    McMahill, B. G., Borjesson, D. L., Sieber-Blum, M., Nolta, J. A., & Sturges, B. K. (2015). Stem cells in canine spinal cord injury – Promise for regenerative therapy in a large animal model of human disease. Stem Cell Reviews and Reports, Feb, 11(1), 180–193.Google Scholar
  52. 52.
    Callera, F., & do Dascimento, R. X. (2006). Delivery of autologous bone marrow precursor cells into spinal cord via lumbar puncture technique in patients with spinal cord injury: A preliminary safety study. Experimental Hematology, 34(2), 130–131.PubMedGoogle Scholar
  53. 53.
    Shieh, H. F., Ahmed, A., Rohrer, L., Zurakowski, D., & Fauza, D. O. (2018). Donor mesenchymal stem cell linetics after transamniotic stem cell therapy (TRASCET) for experimental spina bifida. Journal of Pediatric Surgery, 53(6), 1134–1136.PubMedGoogle Scholar
  54. 54.
    He, L., & Zhang, H. (2019). MicroRNAs in the migration of mesenchymal stem cells. Stem Cell Reviews and Reports, 15(1), 3–12.Google Scholar
  55. 55.
    Shieh, H. F., Tracy, S. A., Hong, C. R., Chalphin, A. V., Ahmed, A., Rohrer, L., et al. (2018). Transamniotic stem cell therapy (TRASCET) in a rabbit model of spina bifida. Journal of Pediatric Surgery, S0022-3468(18), 30746–30742.Google Scholar
  56. 56.
    Vandervelde, S., van Luyn, M. J., Tio, R. A., & Harmsen, M. C. (2005). Signaling factors in stem cell mediated repair of infarcted myocardium. Journal of Molecular Cellular Cardiology, 39(2), 363–376.PubMedGoogle Scholar
  57. 57.
    Gu, W., Zhang, F., Xue, Q., et al. (2010). Transplantation of bone marrow mesenchymal stem cells reduces lesion volume and induces axonal regrowth of injured spinal cord. Neuropathology, 30, 205–217.PubMedGoogle Scholar
  58. 58.
    Sanchez, V., Villalba, N., Fiore, L., Luzzani, C., Miriuka, S., Boveris, S., et al. (2017). Characterization of tunneling nanotubes in Wharton’s jelly mesenchymal stem cells. An intercellular exchange of components between neighboring cells. Stem Cell Reviews and Reports, 13, 491–498.Google Scholar
  59. 59.
    Zhan, J., He, J., Chen, M., Ma, Z., Lu, P., & Yu, B. (2018). Fasudil promotes BMSC migration via activating the MAPK signaling pathway and application in a model of spinal cord injury. Stem Cells International, 2018, 9793845.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Li, F., Xia, W., Yuan, S., & Sun, R. (2009). Acute inhibition of rho-kinase attenuates pulmonary hypertension in patients with congenital heart disease. Pediatric Cardiology, 30, 363–366.PubMedGoogle Scholar
  61. 61.
    Meziane, H., Khelfaoui, M., Morello, N., Hiba, B., Calcagno, E., Reibel-Foisset, S., et al. (2016). Fasudil treatment in adult reverses behavioural changes and brain ventricular enlargement in Oligophrenin-1 mouse model of intellectual disability. Human Molecular Genetics, 25(11), 2314–2323.PubMedGoogle Scholar
  62. 62.
    Petterson, B., Bourke, J., Leonard, H., Jacoby, P., & Bower, C. (2007). Co-occurrence of birth defects and intellectual disability. Paediatric Perinatal Epidemiology, Jan, 21(1), 65–75.Google Scholar
  63. 63.
    Jacob, S. W., & de la Torre, J. C. (2009). Pharmacology of dimethyl sulfoxide in cardiac and CNS damage. Pharmacological Reports, 61, 225–235.PubMedGoogle Scholar
  64. 64.
    Karaça, M., Kiliç, E., Yazici, B., Demir, S., & de la Torre, J. (2002). Ischemic stroke in elderly patients treated with a free radical scavenger–glycolytic intermediate solution: A preliminary pilot trial. Neurological Research, 24, 73–80.PubMedGoogle Scholar
  65. 65.
    Syme, R., Bewick, M., Stewart, D., Porter, K., Chadderton, T., & Glück, S. (2004). The role of depletion of dimethyl sulfoxide before autografting: On hematologic recovery, side effects, and toxicity. Biology of Blood and Marrow Transplantation, 10, 135–141.PubMedGoogle Scholar
  66. 66.
    Akkök, C. A., Holte, M. R., Tangen, J. M., Ostenstad, B., & Bruserud, O. (2009). Hematopoietic engraftment of dimethyl sulfoxide-depleted autologous peripheral blood progenitor cells. Transfusion, 49, 354–361.PubMedGoogle Scholar
  67. 67.
    Junior, A. M., Arrais, C. A., Saboya, R., Velasques, R. D., Junqueira, P. L., & Dulley, F. L. (2008). Neurotoxicity associated with dimethylsulfoxide-preserved hematopoietic progenitor cell infusion. Bone and Marrow Transplantation, 41, 95–96.Google Scholar
  68. 68.
    Mueller, L. P., Theurich, S., Christopeit, M., Grothe, W., Muetherig, A., Weber, T., et al. (2007). Neurotoxicity upon infusion of dimethylsulfoxide-cryopreserved peripheral blood stem cells in patients with and without pre-existing cerebral disease. European Journal of Haematology, 78, 527–531.PubMedGoogle Scholar
  69. 69.
    Windrum, P., & Morris, T. C. M. (2003). Severe neurotoxicity because of dimethyl sulphoxide following peripheral blood stem cell transplantation. Bone and Marrow Transplantation, 31, 315.Google Scholar
  70. 70.
    Hanslick, J. L., Lau, K., Noguchi, K. K., Olney, J. W., Zorumski, C. F., Mennerick, S., & Farber, N. B. (2009). Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system. Neurobiology of Disease, 34, 1–10.PubMedGoogle Scholar
  71. 71.
    Abdelkefi, A., Lakhal, A., Moojat, N., Ben Hamed, L., Fekih, J., Ladeb, S., et al. (2009). Severe neurotoxicity associated with dimethyl sulphoxide following PBSCT. Bone and Marrow Transplantation, 44, 323–324.Google Scholar
  72. 72.
    Gonzalez-Lopez, T. J., Sanchez-Guijo, F. M., Ortın, A., Crusoe, E., Cordoba, I., Corral, M., et al. (2011). Ischemic stroke associated with the infusion of DMSO-cryopreserved auto-PBSCs. Bone and Marrow Transplantation, 46, 1035–1036.Google Scholar
  73. 73.
    Schroeder, T., Fenk, R., Saure, C., Czibere, A., Bruns, I., Zohren, F., et al. (2011). The Mexican way: A feasible approach to avoid DMSO toxicity. Bone an Marrow Transplantation, 46, 469–471.Google Scholar
  74. 74.
    Cho, P. S., Messina, D. J., Hirsh, E. L., Chi, N., Goldman, S. N., Lo, D., et al. (2008). Sachs and Christene A. Huang. Immunogenicity of umbilical cord tissue–derived cells. Blood, 111, 430–438.PubMedGoogle Scholar
  75. 75.
    Ren, G., Zhang, L., Zhao, X., Xu, G., Zhang, Y., Roberts, A. I., et al. (2008). Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell, 2, 141–150.Google Scholar
  76. 76.
    Ren, G., Su, J., Zhang, L., Zhao, X., Ling, W., L'Huillie, A., et al. (2009). Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem Cells, 27, 1954–1962.Google Scholar
  77. 77.
    Shi, Y., Hu, G., Su, J., Li, W., Chen, Q., Shou, C., et al. (2010). Mesenchymal stem cells: A new strategy for immunosuppression and tissue repair. Cell Research, 20, 510–518.PubMedGoogle Scholar
  78. 78.
    Su, J., Chen, X., Huang, Y., Li, W., Li, J., Cao, K., et al. (2014). Phylogenetic distinction of iNOS and IDO function in mesenchymal stem cell-mediated immunosuppression in mammalian species. Cell Death and Differention, 21, 388–396.Google Scholar
  79. 79.
    Almeida-Porada, G. D., Hoffman, R., Manalo, P., Gianni, A. M., & Zanjani, E. D. (1996). Detection of human cells in human/sheep chimeric lambs with in vitro human stroma-forming potential. Experimental Hematology, 24, 482–487.PubMedGoogle Scholar
  80. 80.
    Liechty, K. W., MacKenzie, T. C., Shaaban, A. F., Radu, A., Moseley, A. M., Deans, R., et al. (2000). Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nature Medicine, 6, 1282–1286.PubMedGoogle Scholar
  81. 81.
    Mackenzie, T. C., & Flake, A. W. (2001). Multilineage differentiation of human MSC after in utero transplantation. Cytotherapy, 3, 403–405.PubMedGoogle Scholar
  82. 82.
    Almeida-Porada, G., El Shabrawy, D., Porada, C., & Zanjani, E. D. (2002). Differentiative potential of human metanephric mesenchymal cells. Experimental Hematology, 30, 1454–1462.PubMedGoogle Scholar
  83. 83.
    Snowise, S., Mann, L., Morales, Y., Moise, K. J., Jr., Johnson, A., Fletcher, S., et al. (2017). Cryopreserved human umbilical cord versus biocellulose film for prenatal spina bifida repair in a physiologic rat model. Prenatal Diagnosis, 37(5), 473–481.PubMedGoogle Scholar
  84. 84.
    Wang, A., Brown, E. G., Lankford, L., Keller, B. A., Pivetti, C. D., Sitkin, N. A., et al. (2015). Placental mesenchymal stromal cells rescue ambulation in ovine myelomeningocele. Stem Cells Translational Medicine, 4(6), 659–669.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Mackenzie, T. C., Shaaban, A. F., Radu, A., & Flake, A. W. (2002). Engraftment of bone marrow and fetal liver cells after in utero transplantation in MDX mice. Jorunal of Pediatric Surgery, 37, 1058–1064.Google Scholar
  86. 86.
    Fauza, D. O. (2018). Transamniotic stem cell therapy: A novel strategy for the prenatal management of congenital anomalies. Pediatric Research, 83(1–2), 241–248.PubMedGoogle Scholar
  87. 87.
    Fauza, D. O. (2017). Regenerative medicine and spina bifida: Recent developments in induced fetal regeneration. Issue title: Spina Bifida. Guest editors: Timothy Brei and Amy Houtrow. Journal of Pediatric Rehabilitation Medicine, 10(3–4), 185–188.PubMedGoogle Scholar
  88. 88.
    Boruczkowski, D., Pujal, J.-M., & Zdolińska-Malinowska, I. (2019). Autologous cord blood in children with cerebral palsy: A review. International Journal of Molecular Sciences, 20(10), 2433.PubMedCentralGoogle Scholar
  89. 89.
    Ferreira-Silva, V., Primo, F. L., Baqui, M. M., et al. (2018). The impact of morphine on the characteristics and function properties of human mesenchymal stem cells. Stem Cell Rev and Rep, 14, 585.Google Scholar
  90. 90.
    Holan, V., Cechova, K., Zajicova, A., et al. (2018). Beneficial role of low-intensity laser irradiation on neural β-tubulin III protein expression in human bone marrow multipotent mesenchymal stromal cells. Stem Cell Rev and Rep, 14, 801.Google Scholar
  91. 91.
    Long, C., Lankford, L., & Wang, A. (2019). Stem cell-based in utero therapies for spina bifida: Implications for neural regeneration. Neural Regeneration Research, 14(2), 260–261.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Medical DepartmentPolski Bank Komórek Macierzystych S.A. (FamiCord Group)WarsawPoland

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