Effects of Bone Morphogenetic Proteins on Primary Human Renal Cells and the Generation of Bone Morphogenetic Protein-7-Expressing Cells for Application in Bioartificial Kidneys

• Published in: Tissue engineering. Part A 2012-02, Vol.18 (3-4), p.262-276
• Main Authors: Tasnim, Farah, Kandasamy, Karthikeyan, Muck, Joscha S., bin Ibrahim, Mohammed Shahrudin, Ying, Jackie Y., Zink, Daniele
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Alkaline Phosphatase - metabolism; Animals; BAK protein; Bioreactors; Bone; Bone Morphogenetic Protein 2 - pharmacology; Bone morphogenetic protein 7; Bone Morphogenetic Protein 7 - metabolism; Bone Morphogenetic Protein 7 - secretion; Bones; Cell culture; Cells, Cultured; Clinical trials; Epithelium - drug effects; Epithelium - metabolism; gamma-Glutamyltransferase - metabolism; Gene expression; Gene Expression Regulation - drug effects; Genetic Engineering; Growth factors; Humans; Kidney; Kidney Tubules, Proximal - cytology; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - enzymology; Kidneys; Kidneys, Artificial; Mice; Organ Specificity - drug effects; Original Articles; Osteogenesis - drug effects; Osteogenesis - genetics; Phosphorylation - drug effects; Proteins; Proximal tubules; Recombinant Proteins - pharmacology; Smad Proteins - metabolism; Supplementation; Therapeutic applications; Tissue engineering; Tissue Engineering - methods; Transforming Growth Factor beta - pharmacology; Tubules
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2011.0149

Bioartificial kidneys (BAKs) contain renal cells, and primary human renal proximal tubule cells (HPTCs) have been applied in clinical trials with BAKs. Cell performance within the device is critical. HPTC performance is often compromised under in vitro conditions because of dedifferentiation, transdifferentiation, and tubule formation on substrate surfaces. Herein we tested whether treatments with human recombinant bone morphogenetic protein (BMP)-2 or BMP-7 would improve HPTC performance. We found that both growth factors improved HPTC performance, but more consistent results were obtained with BMP-7. The effects were strongly concentration dependent, and for BMP-7, 25 ng/mL was the optimal concentration, which improved HPTC performance under static and under bioreactor conditions. As an alternative to supplementation with the purified growth factor, we generated HPTCs secreting human recombinant BMP-7. BMP-7 secreted by the cells was bioactive and improved the functional performance of HPTCs, in agreement with our other findings. Together, the results suggested that either supplementation with purified BMP-7 or BMP-7-producing cells could be used to improve cell performance in BAKs. BAKs with BMP-7-producing cells could also be used to deliver the growth factor to kidney patients. Our results suggested that the amount of BMP-7 produced by HPTCs would be sufficient for therapeutic applications.