Int J Stem Cells.  2018 Jun;11(1):141-147. 10.15283/ijsc17077.

The Effect of Umbilical Cord-derived Mesenchymal Stem Cell Transplantation in a Patient with Cerebral Palsy: A Case Report

• Okur SC
• ErdoÄŸan S
• Demir CS
• Günel G
• Karaöz E

• KMID: 2413510
• DOI: http://doi.org/10.15283/ijsc17077

Abstract

BACKGROUND
Cerebral Palsy (CP) is the most common motor disability reason of childhood that occurs secondarily to non-progressive damage in the brain whose development is still ongoing.
METHODS
6-year-old dystonic-spastic male CP patient received allogenic mesenchymal stem cells treatment four times as 1×106/kg in intrathecal and intravenous administration of Umbilical Cord-derived mesenchymal stem cells (UC-MSCs) ways. Before and after the treatment, the patient was followed-up with FIM (Functional Independent Measurement), GMFCS (Gross Motor Function Classification System 88), Tardieu Scale, TCMS (Trunk Control Measurement Scale), MACS (Manual Ability Classification Scale), CFSS (Communication Function Classification System) for 18 months and received intensive rehabilitation.
RESULTS
Improvements were observed especially in functional scales except for the Tardieu Scale, and no adverse effects were detected aside from a slight pain in the back.
CONCLUSION
Wider future case studies on UC-MSCs will enable us to assess the efficacy of UC-MSCs which have positive impacts especially on functional scales.

Keyword

Cerebral palsy; Mesenchymal stem cell; Rehabilitation

MeSH Terms

Administration, Intravenous
Brain
Cerebral Palsy*
Child
Classification
Humans
Male
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stromal Cells*
Rehabilitation
Weights and Measures

Figure

• 

  Fig. 1 Characterization and differentiation of UC-MSCs. (A) Osteogenic differentiation control (B) and mineral nodules that stained by Alizarin Red S, of UC-MSCs cultured in osteogenic differentiation medium. (C) Chondrogenic differentiation control (D) and alcian blue staining of UC-MSCs cultured in chondrogenic differentiation medium. (E) Morphology, (F) adipogenic differentiation control and (G) Oil Red O staining of neutral lipid vacuole formation in UC-MSC cultured in adipogenic differentiation medium. (H) Flow cytometric analysis of cell surface markers of UC-MSCs at P3. (I) Chromosome karyotype analysis of the cultered UC-MSCs.

Reference

References

1. Nelson KB. Can we prevent cerebral palsy? N Engl J Med. 2003; 349:1765–1769. DOI: 10.1056/NEJMsb035364. PMID: 14585946.

2. Koman LA, Smith BP, Shilt JS. Cerebral palsy. Lancet. 2004; 363:1619–1631. DOI: 10.1016/S0140-6736(04)16207-7. PMID: 15145637.

3. Paneth N, Hong T, Korzeniewski S. The descriptive epidemiology of cerebral palsy. Clin Perinatol. 2006; 33:251–267. DOI: 10.1016/j.clp.2006.03.011. PMID: 16765723.

4. Lu D, Mahmood A, Wang L, Li Y, Lu M, Chopp M. Adult bone marrow stromal cells administered intravenously to rats after traumatic brain injury migrate into brain and improve neurological outcome. Neuroreport. 2001; 12:559–563. DOI: 10.1097/00001756-200103050-00025. PMID: 11234763.

5. Longhi L, Zanier ER, Royo N, Stocchetti N, McIntosh TK. Stem cell transplantation as a therapeutic strategy for traumatic brain injury. Transpl Immunol. 2005; 15:143–148. DOI: 10.1016/j.trim.2005.09.003.

6. Azari MF, Mathias L, Ozturk E, Cram DS, Boyd RL, Petratos S. Mesenchymal stem cells for treatment of CNS injury. Curr Neuropharmacol. 2010; 8:316–323. DOI: 10.2174/157015910793358204.

7. Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol. 1976; 4:267–274. PMID: 976387.

8. Ichim TE, Solano F, Lara F, Paris E, Ugalde F, Rodriguez JP, Minev B, Bogin V, Ramos F, Woods EJ, Murphy MP, Patel AN, Harman RJ, Riordan NH. Feasibility of combination allogeneic stem cell therapy for spinal cord injury: a case report. Int Arch Med. 2010; 3:30. DOI: 10.1186/1755-7682-3-30. PMID: 21070647. PMCID: 2989319.

9. Han H, Chang SK, Chang JJ, Hwang SH, Han SH, Chun BH. Intrathecal injection of human umbilical cord blood-derived mesenchymal stem cells for the treatment of basilar artery dissection: a case report. J Med Case Rep. 2011; 5:562. DOI: 10.1186/1752-1947-5-562. PMID: 22136528. PMCID: 3240835.

10. Purandare C, Shitole DG, Belle V, Kedari A, Bora N, Joshi M. Therapeutic potential of autologous stem cell transplantation for cerebral palsy. Case Rep Transplant. 2012; 2012:825289. PMID: 23259143. PMCID: 3505957.

11. Lee AS, Tang C, Rao MS, Weissman IL, Wu JC. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat Med. 2013; 19:998–1004. DOI: 10.1038/nm.3267. PMID: 23921754. PMCID: 3967018.

12. Phermthai T, Thongbopit S, Pokathikorn P, Wichitwiengrat S, Julavijitphong S, Tirawanchai N. Carcinogenicity, efficiency and biosafety analysis in xeno-free human amniotic stem cells for regenerative medical therapies. Cytotherapy. 2017; 19:990–1001. DOI: 10.1016/j.jcyt.2017.04.004. PMID: 28566211.

13. Wang L, Ji H, Zhou J, Xie J, Zhong Z, Li M, Bai W, Li N, Zhang Z, Wang X, Zhu D, Liu Y, Wu M. Therapeutic potential of umbilical cord mesenchymal stromal cells transplantation for cerebral palsy: a case report. Case Rep Transplant. 2013; 2013:146347. PMID: 23533920. PMCID: 3603664.

14. Mehta T, Feroz A, Thakkar U, Vanikar A, Shah V, Trivedi H. Subarachnoid placement of stem cells in neurological disorders. Transplant Proc. 2008; 40:1145–1147. DOI: 10.1016/j.transproceed.2008.03.026. PMID: 18555135.

15. Rengasamy M, Gupta PK, Kolkundkar U, Singh G, Balasubramanian S, SundarRaj S, Chullikana A, Majumdar AS. Preclinical safety & toxicity evaluation of pooled, allogeneic human bone marrow-derived mesenchymal stromal cells. Indian J Med Res. 2016; 144:852–864. DOI: 10.4103/ijmr.IJMR_1842_15.

16. Cruz-Martinez P, Pastor D, Estirado A, Pacheco-Torres J, Martinez S, Jones J. Stem cell injection in the hindlimb skeletal muscle enhances neurorepair in mice with spinal cord injury. Regen Med. 2014; 9:579–591. DOI: 10.2217/rme.14.38. PMID: 25372077.

17. Kim Y, Jo SH, Kim WH, Kweon OK. Antioxidant and anti-inflammatory effects of intravenously injected adipose derived mesenchymal stem cells in dogs with acute spinal cord injury. Stem Cell Res Ther. 2015; 6:229. DOI: 10.1186/s13287-015-0236-5. PMID: 26612085. PMCID: 4660672.

18. Wei CC, Lin AB, Hung SC. Mesenchymal stem cells in regenerative medicine for musculoskeletal diseases: bench, bedside, and industry. Cell Transplant. 2014; 23:505–512. DOI: 10.3727/096368914X678328. PMID: 24816447.

19. Snyder EY, Yoon C, Flax JD, Macklis JD. Multipotent neural precursors can differentiate toward replacement of neurons undergoing targeted apoptotic degeneration in adult mouse neocortex. Proc Natl Acad Sci U S A. 1997; 94:11663–11668. DOI: 10.1073/pnas.94.21.11663. PMID: 9326667. PMCID: 23575.

20. Sankar V, Muthusamy R. Role of human amniotic epithelial cell transplantation in spinal cord injury repair research. Neuroscience. 2003; 118:11–17. DOI: 10.1016/S0306-4522(02)00929-6. PMID: 12676132.

21. Lindvall O, Kokaia Z. Recovery and rehabilitation in stroke: stem cells. Stroke. 2004; 35(11 Suppl 1):2691–2694. DOI: 10.1161/01.STR.0000143323.84008.f4. PMID: 15459434.

22. Broughton BR, Lim R, Arumugam TV, Drummond GR, Wallace EM, Sobey CG. Post-stroke inflammation and the potential efficacy of novel stem cell therapies: focus on amnion epithelial cells. Front Cell Neurosci. 2013; 6:66. DOI: 10.3389/fncel.2012.00066. PMID: 23335880. PMCID: 3547279.

23. Vaquero J, Zurita M, Rico MA, Bonilla C, Aguayo C, Fernández C, Tapiador N, Sevilla M, Morejón C, Montilla J, Martínez F, Marín E, Bustamante S, Vázquez D, Carballido J, Rodríguez A, Martínez P, García C, Ovejero M, Fernández MV. Neurological Cell Therapy Group. Repeated subarachnoid administrations of autologous mesenchymal stromal cells supported in autologous plasma improve quality of life in patients suffering incomplete spinal cord injury. Cytotherapy. 2017; 19:349–359. DOI: 10.1016/j.jcyt.2016.12.002. PMID: 28089079.

24. Goldstein M. The treatment of cerebral palsy: what we know, what we don’t know. J Pediatr. 2004; 145(2 Suppl):S42–S46. DOI: 10.1016/j.jpeds.2004.05.022. PMID: 15292887.