Stem cells for spinal cord regeneration: Current status.
BACKGROUND
Nearly 11,000 cases of spinal cord injury (SCI) are reported in the United States annually. Current management options give a median survival time of 38 years; however, no rehabilitative measures are available. Stem cells have been under constant research given their ability to differentiate into neural cell lines replacing non functional tissue. Efforts have been made to establish new synapses and provide a conducive environment, by grafting cells from autologous and fetal sources; including embryonic or adult stem cells, Schwann cells, genetically modified fibroblasts, bone stromal cells, and olfactory ensheathing cells and combinations/ variants thereof.


METHODS
In order to discuss the underlying mechanism of SCI along with the previously mentioned sources of stem cells in context to SCI, a simple review of literature was conducted. An extensive literature search was conducted using the PubMed data base and online search engines and articles published in the last 15 years were considered along with some historical articles where a background was required.


RESULTS
Stem cell transplantation for SCI is at the forefront with animal and in vitro studies providing a solid platform to enable well-designed human studies. Olfactory ensheathing cells seem to be the most promising; whilst bone marrow stromal cells appear as strong candidates for an adjunctive role.


CONCLUSIONS
The key strategy in developing the therapeutic basis of stem cell transplantation for spinal cord regeneration is to weed out the pseudo-science and opportunism. All the trials should be based on stringent scientific criteria and effort to bypass that should be strongly discouraged at the international level.
Department of Neurosurgery, Aga Khan University Hospital, Stadium Road, P.O. Box 3500, Karachi 74800, Pakistan.
Zain A
ZA
Sobani
Syed A
SA
Quadri
S Ather
SA
Enam
J Neurosci. 1999 Oct 15;19(20):8979-89
10516316
Exp Neurol. 2003 Nov;184(1):313-25
14637102
Science. 1999 Apr 16;284(5413):479-82
10205054
Neurosurg Rev. 2006 Oct;29(4):251-63; discussion 264
16752160
Kidney Int. 2005 Nov;68(5):1927-31
16221167
Nat Med. 2004 Apr;10(4):389-95
15004554
J Neurosci. 2002 Sep 1;22(17):7526-35
12196576
Exp Neurol. 2003 Nov;184(1):373-80
14637107
Iran Biomed J. 2009 Jan;13(1):43-8
19252677
N Engl J Med. 1994 Mar 3;330(9):613-22
7905600
J Neurosci. 2004 Sep 29;24(39):8485-93
15456822
Neurobiol Dis. 2009 Oct;36(1):200-12
19631747
Neuroscience. 1999;93(4):1383-9
10501463
J Cell Sci. 1999 Nov;112 ( Pt 22):4007-16
10547361
Cytotherapy. 2009;11(5):618-30
19548142
Oncogene. 1998 Dec 24;17(25):3341-9
9916996
J Neurotrauma. 1997 Sep;14(9):603-14
9337123
J Invest Dermatol. 1997 Feb;108(2):215-9
9008237
J Biomater Sci Polym Ed. 2008;19(3):325-38
18325234
Acta Neurochir (Wien). 2009 Nov;151(11):1483-92
19499175
J Neurochem. 2002 Sep;82(6):1566-9
12354307
Nature. 2000 Jan 27;403(6768):434-9
10667796
Stem Cells. 2005 Nov-Dec;23(10):1560-70
16081669
Eur J Neurosci. 2008 Nov;28(9):1795-807
18973595
J Spinal Cord Med. 1998 Oct;21(4):309-34
10096045
Results Probl Cell Differ. 2010;51:237-57
19513637
Neurol Res. 2009 Apr;31(3):220-7
19406036
Exp Neurol. 2008 Apr;210(2):331-8
18158149
Brain Res Bull. 1998 Jun;46(3):175-87
9667810
Isr Med Assoc J. 2009 Apr;11(4):201-4
19603590
Acta Neurobiol Exp (Wars). 2009;69(1):12-23
19325637
Curr Opin Neurobiol. 2007 Feb;17(1):120-7
17223033
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2009 Jan;23(1):8-13
19192870
J Neurotrauma. 2006 Mar-Apr;23(3-4):453-67
16629629
Blood. 2003 Aug 15;102(4):1548-9
12900350
Exp Neurol. 1999 Sep;159(1):319-28
10486200
Curr Mol Med. 2009 Nov;9(8):992-1016
19747118
J Neurosci Res. 2002 Sep 15;69(6):925-33
12205685
Hum Immunol. 2009 Jan;70(1):16-23
19010366
Gene Ther. 2009 Oct;16(10):1234-44
19626053
J Neurosurg. 2001 Apr;94(2 Suppl):257-64
11302628
Spine (Phila Pa 1976). 2009 Feb 15;34(4):328-34
19182705
J Neurosci. 2006 Sep 27;26(39):9841-50
17005848
Stem Cells. 2004;22(7):1338-45
15579651
Biochem Biophys Res Commun. 2006 Sep 22;348(2):560-70
16890196
J Neurotrauma. 2006 Mar-Apr;23(3-4):371-83
16629623
J Neurotrauma. 2009 Nov;26(11):2057-69
19469692
NeuroRx. 2004 Jan;1(1):80-100
15717009
Cell Mol Neurobiol. 2006 Oct-Nov;26(7-8):1113-29
16633897
J Neuroimmunol. 1999 Feb 1;94(1-2):1-14
10376931
Neuroreport. 2001 Mar 5;12(3):559-63
11234763
Nat Med. 1997 Jan;3(1):73-6
8986744
Neurochem Res. 2008 Jan;33(1):134-49
17703359
Neuron. 1994 Oct;13(4):805-11
7524558
Biochem Biophys Res Commun. 2007 Jun 29;358(2):637-43
17499609
J Neurotrauma. 2006 Mar-Apr;23(3-4):384-96
16629624
Cell Res. 2006 Apr;16(4):329-36
16617328
Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8999-9004
12861073
J Neurochem. 1985 Jan;44(1):247-54
2856883
Expert Opin Biol Ther. 2009 Oct;9(10):1245-58
19663719
Acta Neuropathol. 1999 Nov;98(5):473-80
10541870
Cell Transplant. 2009;18(1):39-54
19476208
J Neurosurg. 2003 Sep;99(2 Suppl):188-97
12956462
J Neurosci. 2003 Nov 5;23(31):10107-15
14602826
Neuroreport. 2006 Aug 21;17(12):1269-72
16951567
Brain Res. 1981 May 4;211(2):485-91
7237140
J Neurosci Res. 1997 Dec 1;50(5):798-808
9418967
Curr Biol. 1996 Oct 1;6(10):1241-3
8939562
Nat Med. 2006 Jul;12(7):829-34
16783372
Stem Cells. 2001;19(3):180-92
11359943
J Neurosci. 2004 Mar 3;24(9):2143-55
14999065
Neurochem Res. 2009 Jul;34(7):1183-94
19152029
Neurosurg Focus. 2008;24(3-4):E20
18341397
Prog Brain Res. 2002;137:313-32
12440375
Neuroreport. 2008 Aug 27;19(13):1259-63
18695504
Brain. 2009 May;132(Pt 5):1268-76
19286693
J Biol Chem. 1997 Jul 25;272(30):18827-33
9228058
Eur J Pharmacol. 2000 Sep 29;405(1-3):297-302
11033336
Brain Res. 2000 May 26;865(2):283-5
10821933
Cell Biol Int. 2006 Sep;30(9):681-7
16870478
Acta Neurochir (Wien). 2005 Sep;147(9):985-92; discussion 992
16010451
Nature. 2002 Jun 27;417(6892):941-4
12068310
Nat Biotechnol. 2005 Jun;23(6):699-708
15940242
J Neurosci Res. 2004 Jun 15;76(6):834-45
15160395
Science. 1997 Sep 26;277(5334):2000-2
9302296
Cell Mol Biol Lett. 2009;14(3):528-36
19412574
Nature. 1995 Sep 28;377(6547):340-4
7566088
J Trauma. 2008 Jan;64(1):53-9
18188099
J Cell Biol. 1999 May 3;145(3):503-14
10225952
J Neurotrauma. 1995 Feb;12(1):1-21
7783230
Transplantation. 2008 Sep 27;86(6):845-53
18813110
Dev Cell. 2005 Nov;9(5):617-28
16256737
Cytotechnology. 2008 Sep;58(1):33-42
19002775
Tissue Eng Part A. 2010 Jan;16(1):45-54
19614546
Clin Neurol Neurosurg. 2004 Jun;106(3):211-7
15177770
Pharmacol Ther. 1999 Mar;81(3):163-221
10334661
J Neurotrauma. 2004 Apr;21(4):383-93
15115588
Nat Biotechnol. 2007 Jan;25(1):100-6
17206138
Spinal Cord. 2003 Jul;41(7):369-78
12815368
Biochim Biophys Acta. 2006 Nov-Dec;1762(11-12):1128-38
16872810
Microsc Res Tech. 2002 Aug 1;58(3):216-27
12203700
Sci Signal. 2009 Mar 31;2(64):ra14
19336839
Spinal Cord. 1997 Dec;35(12):818-28
9429261
Nature. 2000 Jan 27;403(6768):439-44
10667797
Lancet Neurol. 2002 Jun;1(2):92-100
12849513
Spinal Cord. 2008 Dec;46(12):811-7
18560372
Neuroreport. 2004 May 19;15(7):1105-8
15129154
Nat Methods. 2005 Jun;2(6):455-63
16170868
Curr Stem Cell Res Ther. 2009 Sep;4(3):178-99
19492980
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2009 Jan;23(1):14-20
19192871
Brain Res Brain Res Rev. 2001 Dec;38(1-2):165-91
11750932
Hum Reprod. 2004 Jun;19(6):1450-6
15105397
Proc Natl Acad Sci U S A. 1978 Mar;75(3):1554-8
148651
J Neurocytol. 2002 Jul-Aug;31(6-7):481-95
14501218
Nat Protoc. 2008;3(6):1046-55
18536651
Eur J Neurosci. 1994 May 1;6(5):712-24
8075816
Cell. 1999 Jan 8;96(1):25-34
9989494
Lancet Neurol. 2006 Aug;5(8):688-94
16857574
Tissue Eng Part A. 2008 Jan;14(1):9-17
18333820
Neuron. 1994 Sep;13(3):757-67
7522484
Exp Neurol. 2008 Feb;209(2):378-88
17662717
J Neurotrauma. 2007 Feb;24(2):391-410
17376002
Nature. 2001 Jan 18;409(6818):341-6
11201742
J Neurosci. 2008 Nov 12;28(46):11998-2009
19005065
Nature. 2000 Jan 27;403(6768):383-4
10667780
Stem Cells. 2009 Aug;27(8):1879-86
19544448
Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2965-9
8385353
J Neurotrauma. 2003 Jan;20(1):43-57
12614587
Glia. 2003 Feb;41(3):224-36
12528178
Cell Transplant. 2009;18(10):1171-81
19660174
J Neurotrauma. 2004 Jun;21(6):754-74
15253803
Nature. 2002 Nov 7;420(6911):74-8
12422217
Stem Cells Dev. 2006 Jun;15(3):391-406
16846376
Neurosurg Focus. 2008;24(3-4):E19
18341395
J Neurotrauma. 2007 Jan;24(1):216-25
17263685
Exp Biol Med (Maywood). 2009 Oct;234(10):1230-43
19546356
Science. 2002 Aug 16;297(5584):1190-3
12089450
Biochem Soc Trans. 1997 May;25(2):405-10
9191126
Nat Rev Neurosci. 2006 Aug;7(8):617-27
16858390
Exp Neurol. 2004 Jun;187(2):329-36
15144859
J Neurosci. 1997 Jul 15;17(14):5395-406
9204923
Semin Fetal Neonatal Med. 2005 Jun;10(3):209-20
15927877
Curr Opin Neurobiol. 2004 Feb;14(1):118-24
15018947
Nat Med. 2006 Dec;12(12):1380-9
17099709
J Neurotrauma. 2006 Mar-Apr;23(3-4):345-59
16629621
Nat Med. 1996 Dec;2(12):1306-7
8946823
J Clin Neurosci. 2008 Jun;15(6):656-64
18406145
Iran Biomed J. 2009 Jul;13(3):125-35
19688018
Cytotherapy. 2008;10(6):551-64
18608352
J Neurosci. 2003 Jul 2;23(13):5393-406
12843238
Neuron. 1988 Oct;1(8):623-34
2908446
Cytotherapy. 2005;7(4):368-73
16162459
J Neurotrauma. 2001 Aug;18(8):813-9
11526987
Acta Neurobiol Exp (Wars). 2006;66(4):321-9
17269167
Acta Neurobiol Exp (Wars). 2006;66(4):279-91
17265690
Iran Biomed J. 2009 Apr;13(2):117-23
19471552
Methods Mol Med. 2007;140:33-65
18085202
Brain. 2008 Sep;131(Pt 9):2376-86
18689435
Adv Physiol Educ. 2002 Dec;26(1-4):238-55
12443996
J Mater Sci Mater Med. 2009 Oct;20(10):2129-37
19434481
J Neurosci. 2003 May 15;23(10):4219-27
12764110
J Neurosci. 2006 Oct 18;26(42):10856-67
17050723
Nature. 2002 Apr 11;416(6881):636-40
11948352
Glia. 2000 Sep;31(3):241-8
10941150
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3513-8
11248109
Nat Biotechnol. 2006 Mar;24(3):344-50
16444268
Brain Pathol. 1995 Oct;5(4):407-13
8974623
Brain Res. 1991 May 3;547(2):344-8
1884213
J Neurotrauma. 2009 Dec;26(12):2313-22
19645530
Curr Neurol Neurosci Rep. 2009 Jul;9(4):292-7
19515281