TY - JOUR
T1 - Stem cell therapies benefit Alport syndrome
AU - LeBleu, Valerie
AU - Sugimoto, Hikaru
AU - Mundel, Thomas M.
AU - Gerami-Naini, Behzad
AU - Finan, Elizabeth
AU - Miller, Caroline A.
AU - Gattone, Vincent H.
AU - Lu, Lingge
AU - Shield, Charles F.
AU - Folkman, Judah
AU - Kalluri, Raghu
PY - 2009/11
Y1 - 2009/11
N2 - 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 α3 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 α3(IV) chain. These data provide further support for testing cell-based therapies for Alport syndrome.
AB - 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 α3 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 α3(IV) chain. These data provide further support for testing cell-based therapies for Alport syndrome.
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U2 - 10.1681/ASN.2009010123
DO - 10.1681/ASN.2009010123
M3 - Article
C2 - 19833902
AN - SCOPUS:72049083762
SN - 1046-6673
VL - 20
SP - 2359
EP - 2370
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 11
ER -