Transplantation and magnetic resonance imaging of canine neural progenitor cell grafts in the postnatal dog brain.
Cellular transplantation in the form of bone marrow has been one of the primary treatments of many lysosomal storage diseases (LSDs). Although bone marrow transplantation can help central nervous system manifestations in some cases, it has little impact in many LSD patients. Canine models of neurogenetic LSDs provide the opportunity for modeling central nervous system transplantation strategies in brains that more closely approximate the size and architectural complexity of the brains of children. Canine olfactory bulb-derived neural progenitor cells (NPCs) isolated from dog brains were expanded ex vivo and implanted into the caudate nucleus/thalamus or cortex of allogeneic dogs. Canine olfactory bulb-derived NPCs labeled with micron-sized superparamagnetic iron oxide particles were detected by magnetic resonance imaging both in vivo and postmortem. Grafts expressed markers of NPCs (i.e. nestin and glial fibrillary acidic protein), but not the neuronal markers Map2ab or beta-tubulin III. The NPCs were from dogs with the LSD mucopolysaccharidosis VII, which is caused by a deficiency of beta-glucuronidase. When mucopolysaccharidosis VII canine olfactory bulb-NPCs that were genetically corrected with a lentivirus vector ex vivo were transplanted into mucopolysaccharidosis VII recipient brains, they were detected histologically by beta-glucuronidase expression in areas identified by antemortem magnetic resonance imaging tracking. These results demonstrate the potential for ex vivo stem cell-based gene therapy and noninvasive tracking of therapeutic grafts in vivo.
Walton
Raquel M
RM
W. F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, Department of Pathobiology, University of Pennsylvania; Stokes Institute, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Magnitsky
Sergey G
SG
Seiler
Gabriela S
GS
Poptani
Harish
H
Wolfe
John H
JH
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology*; D004285:Dogs; D004798:Enzymes / Q000378:metabolism; D005290:Ferric Compounds; D005819:Genetic Markers; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D016538:Mucopolysaccharidosis VII / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D053758:Nanoparticles; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000637:transplantation*; D009830:Olfactory Bulb / Q000166:cytology; D010641:Phenotype; D033581:Stem Cell Transplantation; D014404:Tubulin / Q000378:metabolism; D014463:Ultrasonography
D004798:Enzymes; D005290:Ferric Compounds; D005819:Genetic Markers; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D014404:Tubulin; C000499:ferric oxide; D019950:Mitogen-Activated Protein Kinase 1
Genomics. 1999 Jun 1;58(2):121-8
10366443
Nat Med. 1998 Nov;4(11):1313-7
9809557
Exp Neurol. 1999 Aug;158(2):265-78
10415135
Science. 1962 Mar 30;135(3509):1127-8
13860748
J Neurosci. 2004 Nov 24;24(47):10642-51
15564580
J Neurotrauma. 2004 Oct;21(10):1479-99
15672637
Br J Haematol. 2005 Feb;128(4):413-31
15686451
Magn Reson Med. 2005 Feb;53(2):329-38
15678543
Neuroimage. 2005 Jul 1;26(3):744-54
15955483
Nat Rev Neurosci. 2005 Sep;6(9):713-25
16049428
Mol Ther. 2006 Mar;13(3):548-55
16316785
Hum Gene Ther. 2006 Jul;17(7):693-704
16839269
Acta Paediatr Suppl. 2007 Apr;96(455):26-32
17391436
Exp Neurol. 1999 Nov;160(1):17-27
10630187
Ann Neurol. 1999 Dec;46(6):867-77
10589539
Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15256-61
10611372
J Neurosci. 2000 Dec 1;20(23):8727-35
11102479
Mol Ther. 2001 Feb;3(2):139-48
11237670
Ann Neurol. 2002 Dec;52(6):762-70
12447930
J Comp Neurol. 2003 May 12;459(4):368-91
12687705
Nature. 2003 Apr 17;422(6933):688-94
12700753
Blood. 2003 Aug 1;102(3):867-72
12676779
J Neurosci Res. 2003 Oct 15;74(2):266-77
14515356
Exp Neurol. 2003 Oct;183(2):653-64
14552907
Mol Cell Neurosci. 2003 Dec;24(4):1074-82
14697670
Nat Rev Mol Cell Biol. 2004 Jul;5(7):554-65
15232573
Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):10901-6
15256592
Gene Ther. 2004 Oct;11(19):1475-81
15295619
J Comp Neurol. 1965 Jun;124(3):319-35
5861717
J Pediatr. 1973 Feb;82(2):249-57
4265197
Pediatr Res. 1984 Oct;18(10):980-4
6436780
J Neurosci. 1988 Apr;8(4):1144-51
3357014
J Clin Invest. 1989 Apr;83(4):1258-66
2495302
Annu Rev Biochem. 1991;60:257-80
1883197
Cell. 1992 Jan 10;68(1):33-51
1732063
Science. 1992 Mar 27;255(5052):1707-10
1553558
Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8591-5
1528866
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3602-6
8475109
Nat Genet. 1992 Aug;1(5):379-84
1338772
Science. 1994 May 20;264(5162):1145-8
8178174
Vet Pathol. 1994 Jul;31(4):435-43
7941232
Nature. 1995 Mar 23;374(6520):367-70
7885477
Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11879-83
8524867
Exp Neurol. 1996 Feb;137(2):376-88
8635554
Science. 1996 Apr 12;272(5259):263-7
8602510
Dev Biol. 1996 Apr 10;175(1):1-13
8608856
Nature. 1996 Oct 17;383(6601):624-7
8857538
Mol Cell Neurosci. 1997;8(6):389-404
9143557
Nat Med. 1997 Jul;3(7):771-4
9212105
Brain Pathol. 1998 Jan;8(1):175-93
9458175
Am J Vet Res. 1998 Sep;59(9):1092-5
9736382
Nat Biotechnol. 1998 Nov;16(11):1033-9
9831031
Lab Invest. 1998 Dec;78(12):1575-81
9881957
JAMA. 1999 Jan 20;281(3):249-54
9918480
Exp Neurol. 1999 Mar;156(1):71-83
10192778
NMR Biomed. 2007 May;20(3):275-90
17451181
Neurodegener Dis. 2007;4(4):314-21
17627135
J Neuropathol Exp Neurol. 2007 Aug;66(8):760-9
17882020
J Neurosci Methods. 2008 Mar 30;169(1):158-67
18261803
Circulation. 2008 Mar 25;117(12):1555-62
18332264
Biochem Biophys Res Commun. 2008 May 16;369(4):1076-81
18336785
J Neurosci. 1999 Jul 15;19(14):5990-6005
10407037