Stem cell therapies benefit Alport syndrome.
Patients with Alport syndrome progressively lose renal function as a result of defective type IV collagen in their glomerular basement membrane. In mice lacking the alpha3 chain of type IV collagen (Col4A3 knockout mice), a model for Alport syndrome, transplantation of wild-type bone marrow repairs the renal disease. It is unknown whether cell-based therapies that do not require transplantation have similar potential. Here, infusion of wild-type bone marrow-derived cells into unconditioned, nonirradiated Col4A3 knockout mice during the late stage of disease significantly improved renal histology and function. Furthermore, transfusion of unfractionated wild-type blood into unconditioned, nonirradiated Col4A3 knockout mice improved the renal phenotype and significantly improved survival. Injection of mouse and human embryonic stem cells into Col4A3 knockout mice produced similar results. Regardless of treatment modality, the improvement in the architecture of the glomerular basement membrane is associated with de novo expression of the alpha3(IV) chain. These data provide further support for testing cell-based therapies for Alport syndrome.
LeBleu
Valerie
V
Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Sugimoto
Hikaru
H
Mundel
Thomas M
TM
Gerami-Naini
Behzad
B
Finan
Elizabeth
E
Miller
Caroline A
CA
Gattone
Vincent H
VH
Lu
Lingge
L
Shield
Charles F
CF
Folkman
Judah
J
Kalluri
Raghu
R
D000818:Animals; D001324:Autoantigens / Q000235:genetics; D001854:Bone Marrow Cells; D024141:Collagen Type IV / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009394:Nephritis, Hereditary / Q000601:surgery*; D033581:Stem Cell Transplantation
D001324:Autoantigens; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain