Stem cell therapies benefit Alport syndrome

Valerie LeBleu, Hikaru Sugimoto, Thomas M. Mundel, Behzad Gerami-Naini, Elizabeth Finan, Caroline A. Miller, Vincent H. Gattone, Lingge Lu, Charles F. Shield, Judah Folkman, Raghu Kalluri

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2359-2370
Number of pages12
JournalJournal of the American Society of Nephrology
Volume20
Issue number11
DOIs
StatePublished - Nov 1 2009

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Hereditary Nephritis
Cell- and Tissue-Based Therapy
Knockout Mice
Stem Cells
Kidney
Glomerular Basement Membrane
Collagen Type IV
Bone Marrow Transplantation
Bone Marrow Cells
Histology
Transplantation
Phenotype
Injections
Survival

ASJC Scopus subject areas

  • Nephrology

Cite this

LeBleu, V., Sugimoto, H., Mundel, T. M., Gerami-Naini, B., Finan, E., Miller, C. A., ... Kalluri, R. (2009). Stem cell therapies benefit Alport syndrome. Journal of the American Society of Nephrology, 20(11), 2359-2370. https://doi.org/10.1681/ASN.2009010123

Stem cell therapies benefit Alport syndrome. / LeBleu, Valerie; Sugimoto, Hikaru; Mundel, Thomas M.; Gerami-Naini, Behzad; Finan, Elizabeth; Miller, Caroline A.; Gattone, Vincent H.; Lu, Lingge; Shield, Charles F.; Folkman, Judah; Kalluri, Raghu.

In: Journal of the American Society of Nephrology, Vol. 20, No. 11, 01.11.2009, p. 2359-2370.

Research output: Contribution to journalArticle

LeBleu, V, Sugimoto, H, Mundel, TM, Gerami-Naini, B, Finan, E, Miller, CA, Gattone, VH, Lu, L, Shield, CF, Folkman, J & Kalluri, R 2009, 'Stem cell therapies benefit Alport syndrome', Journal of the American Society of Nephrology, vol. 20, no. 11, pp. 2359-2370. https://doi.org/10.1681/ASN.2009010123
LeBleu V, Sugimoto H, Mundel TM, Gerami-Naini B, Finan E, Miller CA et al. Stem cell therapies benefit Alport syndrome. Journal of the American Society of Nephrology. 2009 Nov 1;20(11):2359-2370. https://doi.org/10.1681/ASN.2009010123
LeBleu, Valerie ; Sugimoto, Hikaru ; Mundel, Thomas M. ; Gerami-Naini, Behzad ; Finan, Elizabeth ; Miller, Caroline A. ; Gattone, Vincent H. ; Lu, Lingge ; Shield, Charles F. ; Folkman, Judah ; Kalluri, Raghu. / Stem cell therapies benefit Alport syndrome. In: Journal of the American Society of Nephrology. 2009 ; Vol. 20, No. 11. pp. 2359-2370.
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