Transplanted Oligodendrocytes and Motoneuron Progenitors Generated from Human Embryonic Stem Cells Promote Locomotor Recovery After Spinal Cord Transection

Abstract

Human embryonic stem cells (hESC) hold great promise for the treatment of patients with many neurodegenerative diseases particularly those arising from cell loss or neural dysfunction including spinal cord injury. This study evaluates the therapeutic effects of transplanted hESC-derived oligodendrocyte progenitors (OPC) and/or motoneuron progenitors (MP) on axonal remyelination and functional recovery of adult rats after complete spinal cord transection. OPC and/or MP were grafted into the site of injury in the acute phase. Based on Basso-Beattie-Bresnahan scores recovery of locomotor function was significantly enhanced in rats treated with OPC and/or MP when compared with control animals. When transplanted into the spinal cord immediately after complete transection, OPC and MP survived, migrated, and differentiated into mature oligodendrocytes and neurons showing in vivo electrophysiological activity. Taken together, these results indicate that OPC and MP derived from hESC could be a useful therapeutic strategy to repair injured spinal cord.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 54

1. 1.

   Beattie MS, Li Q, Bresnahan JC. Cell death and plasticity after experimental spinal cord injury. Prog Brain Res. 2000;128:9-21.

   Not in our library10.1016/s0079-6123(00)28003-5

2. 2.

   Blight AR. Spinal cord injury models: Neurophysiology. J Neurotrauma. 1992;9:147-149.

   Not in our library10.1089/neu.1992.9.147

3. 3.

   Grossman SD, Rosenberg LJ, Wrathall JR. Relationship of altered glutamate receptor subunit mRNA expression to acute cell loss after spinal cord contusion. Exp Neurol. 2001;168:283-289.

   Not in our library10.1006/exnr.2001.7629

4. 4.

   Deumens R, Koopmans GC, Jaken RJ, et al. Stimulation of neurite outgrowth on neonatal cerebral astrocytes is enhanced in the presence of BDNF. Neurosci Lett. 2006;407:268-273.

   Not in our library10.1016/j.neulet.2006.08.059

5. 5.

   Dietz V, Curt A. Neurological aspects of spinal-cord repair: Promises and challenges. Lancet Neurol. 2006;5:688-694.

   Not in our library10.1016/s1474-4422(06)70522-1

6. 6.

   Harel NY, Strittmatter SM. Can regenerating axons recapitulate developmental guidance during recovery from spinal cord injury? Nat Rev Neurosci. 2006;7:603-616.

   Not in our library10.1038/nrn1957

7. 7.

   Benzing C, Segschneider M, Leinhaas A, et al. Neural conversion of human embryonic stem cell colonies in the presence of fibroblast growth factor-2. Neuroreport. 2006;17:1675-1681.

   Not in our library10.1097/01.wnr.0000236861.01210.72

8. 8.

   Gerrard L, Rodgers L, Cui W. Differentiation of human embryonic stem cells to neural lineages in adherent culture by blocking bone morphogenetic protein signaling. Stem Cells. 2005;23:1234-1241.

   Not in our library10.1634/stemcells.2005-0110

9. 9.

   Itsykson P, Ilouz N, Turetsky T, et al. Derivation of neural precursors from human embryonic stem cells in the presence of noggin. Mol Cell Neurosci. 2005;30:24-36.

   Not in our library10.1016/j.mcn.2005.05.004

10. 10.

    Keirstead HS, Nistor G, Bernal G, et al. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci. 2005;25:4694-4705.

    Not in our library10.1523/jneurosci.0311-05.2005

11. 11.

    Lee H, Shamy GA, Elkabetz Y, et al. Directed differentiation and transplantation of human embryonic stem cell-derived motoneurons. Stem Cells. 2007;25:1931-1939.

    Not in our library10.1634/stemcells.2007-0097

12. 12.

    Li XJ, Du ZW, Zarnowska ED, et al. Specification of motoneurons from human embryonic stem cells. Nat Biotechnol. 2005;23:215-221.

    Not in our library10.1038/nbt1063

13. 13.

    Ludwig TE, Levenstein ME, Jones JM, et al. Derivation of human embryonic stem cells in defined conditions. Nat Biotechnol. 2006;24:185-187.

    Not in our library10.1038/nbt1177

14. 14.

    Erceg S, Lainez S, Ronaghi M, et al. Differentiation of human embryonic stem cells to regional specific neural precursors in chemically defined medium conditions. Plos One. 2008;3:e2122.

    Not in our library10.1371/journal.pone.0002122

15. 15.

    Deshpande DM, Kim YS, Martinez T, et al. Recovery from paralysis in adult rats using embryonic stem cells. Ann Neurol. 2006;60:32-44.

    Not in our library10.1002/ana.20901

16. 16.

    Harper JM, Krishnan C, Darman JS, et al. Axonal growth of embryonic stem cell-derived motoneurons in vitro and in motoneuron-injured adult rats. Proc Natl Acad Sci USA. 2004;101:7123-7128.

    Not in our library10.1073/pnas.0401103101

17. 17.

    Liu S, Qu Y, Stewart TJ, et al. Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation. Proc Natl Acad Sci USA. 2000;97:6126-6131.

    Not in our library10.1073/pnas.97.11.6126

18. 18.

    McDonald JW, Liu XZ, Qu Y, et al. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med. 1999;5:1410-1412.

    Not in our library10.1038/70986

19. 19.

    Nistor GI, Totoiu MO, Haque N, et al. Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia. 2005;49:385-396.

    Not in our library10.1002/glia.20127

20. 20.
    Acute and delayed transplantation of olfactory ensheathing cells promote partial recovery after complete transection of the spinal cord · 2006

    Not checked
21. 21.

    Ramon-Cueto A, Cordero MI, Santos-Benito FF, et al. Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron. 2000;25:425-435.

    Not in our library10.1016/s0896-6273(00)80905-8

22. 22.

    Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995;12:1-21.

    Not in our library10.1089/neu.1995.12.1

23. 23.

    Oria M, Raguer N, Chatauret N, et al. Functional abnormalities of the motor tract in the rat after portocaval anastomosis and after carbon tetrachloride induction of cirrhosis. Metab Brain Dis. 2006;21:297-308.

    Not in our library10.1007/s11011-006-9036-z

24. 24.

    Oria M, Chatauret N, Raguer N, et al. A new method for measuring motor evoked potentials in the awake rat: Effects of anesthetics. J Neurotrauma. 2008;25:266-275.

    Not in our library10.1089/neu.2007.0393

25. 25.

    Kakulas BA. The applied neuropathology of human spinal cord injury. Spinal Cord. 1999;37:79-88.

    Not in our library10.1038/sj.sc.3100807

26. 26.

    Basso DM, Beattie MS, Bresnahan JC. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol. 1996;139:244-256.

    Not in our library10.1006/exnr.1996.0098

27. 27.

    Garcia-Alias G, Verdu E, Fores J, et al. Functional and electrophysiological characterization of photochemical graded spinal cord injury in the rat. J Neurotrauma. 2003;20:501-510.

    Not in our library10.1089/089771503765355568

28. 28.
    Transplantation of Human Umbilical Mesenchymal Stem Cells from Wharton's Jelly after Complete Transection of the Rat Spinal Cord · 2008

    No notice
29. 29.

    Shihabuddin LS, Horner PJ, Ray J, et al. Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J Neurosci. 2000;20:8727-8735.

    Not in our library10.1523/jneurosci.20-23-08727.2000

30. 30.

    Song H, Stevens CF, Gage FH. Astroglia induce neurogenesis from adult neural stem cells. Nature. 2002;417:39-44.

    Not in our library10.1038/417039a

31. 31.

    Horner PJ, Power AE, Kempermann G, et al. Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. J Neurosci. 2000;20:2218-2228.

    Not in our library10.1523/jneurosci.20-06-02218.2000

32. 32.

    Bito H, Furuyashiki T, Ishihara H, et al. A critical role for a Rho-associated kinase, p160ROCK, in determining axon outgrowth in mammalian CNS neurons. Neuron. 2000;26:431-441.

    Not in our library10.1016/s0896-6273(00)81175-7

33. 33.

    Pearse DD, Pereira FC, Marcillo AE, et al. cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nat Med. 2004;10:610-616.

    Not in our library10.1038/nm1056

34. 34.

    Hannila SS, Filbin MT. The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. Exp Neurol. 2008;209:321-332.

    Not in our library10.1016/j.expneurol.2007.06.020

35. 35.

    Nikulina E, Tidwell JL, Dai HN, et al. The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc Natl Acad Sci USA. 2004;101:8786-8790.

    Not in our library10.1073/pnas.0402595101

36. 36.

    Gomez-Pinilla F, Ying Z, Opazo P, et al. Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and skeletal muscle. Eur J Neurosci. 2001;13:1078-1084.

    Not in our library10.1046/j.0953-816x.2001.01484.x

37. 37.

    Gomez-Pinilla F, Ying Z, Roy RR, et al. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol. 2002;88:2187-2195.

    Not in our library10.1152/jn.00152.2002

38. 38.

    Ying Z, Roy RR, Edgerton VR, et al. Voluntary exercise increases neurotrophin-3 and its receptor TrkC in the spinal cord. Brain Res. 2003;987:93-99.

    Not in our library10.1016/s0006-8993(03)03258-x

39. 39.

    Kubasak MD, Jindrich DL, Zhong H, et al. OEG implantation and step training enhance hindlimb-stepping ability in adult spinal transected rats. Brain. 2008;131:264-276.

    Not in our library10.1093/brain/awm267

40. 40.

    Valero-Cabre A, Fores J, Navarro X. Reorganization of reflex responses mediated by different afferent sensory fibers after spinal cord transection. J Neurophysiol. 2004;91:2838-2848.

    Not in our library10.1152/jn.01177.2003

Cited by papers we hold 1

• Neural Stem Cell-Conditioned Medium Protects Neurons and Promotes Propriospinal Neurons Relay Neural Circuit Reconnection after Spinal Cord Injury · 2014
  Not checked

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.