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Table 3 Selected pre-clinical studies of growth factors therapy for sphincter dysfunctions

From: Stem cell therapy combined with controlled release of growth factors for the treatment of sphincter dysfunction

Goal of studies

Animal model

Growth factors/ deliver methods

Main outcomes

Conclusions

Urethral sphincter

 Determined the effects of controlled release of IGF-1 from A-PLO-G microbeads on external urethral sphincter tissue regeneration in a rat model of SUI

Rats/ VD

1 × 104 IGF-1-A-PLO-G microbeads/ Periurethral injection [193]

↑ LPP,

↑ Ske-M,

↑ Vas

Periurethral administration of IGF-1-A-PLO-G microbeads facilitated recovery from SUI by promoting skeletal myogenesis and revascularization

 Evaluated the effects of sustained release bFGF injection in rat urethra

Rats/ urethra denervated by Botox

50 and 200 μg bFGF in gelatin hydrogels/ Periurethral injection [240]

↑ LPP,

↑ Ske-M,

↑ Sm-M,

↑ Vas

Sustained release bFGF injection in the chemically denervated urethral sphincter facilitated regeneration of the urethral muscles and improved sphincteric contractility

 Investigated the ability of neurotrophin therapy to facilitate recovery of the neuromuscular continence mechanism

Rats/ PNC + VD

2 μg BDNF/ day/ Subcutaneous miniature-osmotic pumps [12]

↑ LPP,

↑ Ske-M,

↑ Peri-N

Continuous targeted neurotrophin therapy accelerated continence recovery after simulated childbirth injury

 Investigated the growth factor-immobilized porous beads as an injectable urethral bulking agent

Rats/ sciatic nerve transection

20 μl bFGF or VEGF immobilized porous beads/ Periurethral injections [241]

↑ LPP,

↑ Sm-M,

↑ contract

Growth factor-immobilized porous beads were a good candidate as an injectable bioactive bulking agent

 Investigated the effect of dual growth factor-loaded in situ gel-forming bulking agent for the treatment of SUI

Rats/ sciatic nerve transection

20 μl NGF and/ or bFGF loaded bulking agents/ Periurethral injections [242]

↑ LPP,

↑ Sm-M,

↑ Peri-N,

↑ contract

NGF/ bFGF-loaded in situ gel-forming bulking agent might be a promising injectable bioactive system for the treatment for SUI

 Assessed whether HGF combined with IGF-1 promote the activation, proliferation, and differentiation of satellite cells

Rats

10 μl IGF-1 (50 μg/ ml) and 10 μl HGF (20, 50, 100 μg/ ml)/ Periurethral injections [243]

↑ Ske-M

Synergistic effect of HGF and IGF-1 injection on skeletal muscle regeneration

Anal sphincter

 Investigated effects of IGF-I gene therapy on the injured rat pudendal nerve

Rats/ PNC

25 μl recombinant human IGF-1 plasmid (75 mg DNA dose)/ IM [244]

↑ Peri-N

IGF-I gene therapy might improve the distal recovery of structure and function of pudendal nerve

 Compared several growth factors to optimize the growth and survival of a bioengineered internal anal sphincter

Mice

10 μg of FGF-2, 2 μg of VEGF or 2 μg of PDGF/ Subcutaneous micro-osmotic pump [245]

↑ Sm-M,

↑ Vas

All growth factors displayed encouraging performance, particularly PDGF-supplemented implants after in vivo implantation

  1. A-PLO-G alginate-poly-L-ornithine-gelatine, BDNF brain-derived neurotrophic factor, bFGF basic fibroblast growth factor, Botox botulinum-A toxin, HGF hepatocyte growth factor, IGF-1 insulin-like growth factors 1, IM intramuscular, LPP leak point pressure, NGF nerve growth factor, PDGF platelet-derived growth factor, Peri-N peripheral neurogenesis, PNC pudendal nerve crush, Ske-M skeletal myogenesis, Sm-M smooth muscle myogenesis, Vas vascularization, VD vaginal dilation, VEGF vascular endothelial growth factor; ↑: increased