A platform technique for growth factor delivery with novel mode of action

Kim, Nam Hee; Hoon, Yong; Kim, Hyun Sil; Lee, Soo Eon; Huh, Jong-Ki; Kim, Jung Kook; Kim, Jeong Moon; Ryu, Joo Kyung; Kim, Hee Jin; Lee, Yoonmi; Lee, Su Yeon; Noh, Insup; Li, Xiao Yan; Weiss, Stephen J.; Jahng, Tae-Ahn; Yook, Jong In

doi:10.1016/j.biomaterials.2014.08.005

Cited by 11 publications

(20 citation statements)

References 44 publications

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“…In fact, PTD-BMP-2 was functional during in vivo bone regeneration, with only a few micrograms being sufficient for the process. 12 In line with these findings, the PTD-BMP-7 dosage (10 μg/wk) instilled intra-peritoneally in the present study was significantly smaller when compared to the rBMP-7 dosage (100-300 μg/kg/d) used to treat peritoneal fibrosis in PD rat models in other studies. 3,32 An EMT-suppressing effect was observed with the PTD-BMP-7 dose used in this study.…”

Section: F I G U R Esupporting

confidence: 89%

“…The bacterial expression cassette for the PTD-fusion BMP-7 polypeptide and the purification procedures have been described previously. 12 HPMCs were isolated in accordance with the process stated by Stylianou et al 19…”

Section: Bacterial Expression Production Of Ptd-bmp-7 and Isolatimentioning

confidence: 99%

“…14 Recently, we developed a PTD-based rBMP-2 polypeptide (PTD-BMP-2) to delivery polypeptides into cells, followed by furin-mediated protein cleavage and secretion of active growth factors from the cells. 12 The study demonstrated an indirect delivery system using a PTD-protein, thereby mimicking endogenous protein biogenesis. As a denatured polypeptide, the prodrug was also resistant to proteolytic degradation via body fluids.…”

Section: F I G U R Ementioning

confidence: 99%

“…For example, unlike in vitro culture dish, intra-peritoneal administration of soluble and bioactive rBMP-7 in vivo inevitably leads to their initial burst release and short half-life because of rapid clearance by body fluid and proteolytic degradation. [10][11][12] Because of these limitations, excess dosages of rBMP-7 are often administered to achieve clinical effectiveness. Therefore, a high dosage of rBMP-7, during a long-term regeneration period (often several weeks), inevitably increases the possibility of spreading to nearby tissues or blood circulation with many adverse effects, while remaining cost-ineffective.…”

Section: Introductionmentioning

confidence: 99%

“…[16][17][18] We have previously reported that PTDmediated transduction of BMP provides a novel drug delivery model overcoming limitations of current soluble recombinant proteins. 12 Therefore, this study was undertaken to evaluate the effect of PTD-BMP-7 on TGF-β1-induced EMT in cultured human peritoneal mesothelial cells (HPMCs). Furthermore, the effects of PTD-BMP-7 on EMT and peritoneal fibrosis were investigated in peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis animal models.…”

Section: Introductionmentioning

confidence: 99%

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Newly designed Protein Transduction Domain (PTD)‐mediated BMP‐7 is a potential therapeutic for peritoneal fibrosis

Kim

Shin

Nam

et al. 2020

J Cellular Molecular Medi

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While the bone morphogenetic protein‐7 (BMP‐7) is a well‐known therapeutic growth factor reverting many fibrotic diseases, including peritoneal fibrosis by peritoneal dialysis (PD), soluble growth factors are largely limited in clinical applications owing to their short half‐life in clinical settings. Recently, we developed a novel drug delivery model using protein transduction domains (PTD) overcoming limitation of soluble recombinant proteins, including bone morphogenetic protein‐7 (BMP‐7). This study aims at evaluating the therapeutic effects of PTD‐BMP‐7 consisted of PTD and full‐length BMP‐7 on epithelial‐mesenchymal transition (EMT)‐related fibrosis. Human peritoneal mesothelial cells (HPMCs) were then treated with TGF‐β1 or TGF‐β1 + PTD‐BMP‐7. Peritoneal dialysis (PD) catheters were inserted into Sprague‐Dawley rats, and these rats were infused intra‐peritoneally with saline, peritoneal dialysis fluid (PDF) or PDF + PTD‐BMP‐7. In vitro, TGF‐β1 treatment significantly increased fibronectin, type I collagen, α‐SMA and Snail expression, while reducing E‐cadherin expression in HPMCs (P < .001). PTD‐BMP‐7 treatment ameliorated TGF‐β1‐induced fibronectin, type I collagen, α‐SMA and Snail expression, and restored E‐cadherin expression in HPMCs (P < .001). In vivo, the expressions of EMT‐related molecules and the thickness of the sub‐mesothelial layer were significantly increased in the peritoneum of rats treated with PDF, and these changes were significantly abrogated by the intra‐peritoneal administration of PTD‐BMP‐7. PTD‐BMP‐7 treatment significantly inhibited the progression of established PD fibrosis. These findings suggest that PTD‐BMP‐7, as a prodrug of BMP‐7, can be an effective therapeutic agent for peritoneal fibrosis in PD patients.

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Section: F I G U R Esupporting

confidence: 89%

Section: Bacterial Expression Production Of Ptd-bmp-7 and Isolatimentioning

confidence: 99%