Engineering of pre‐vascularized urethral patch with muscle flaps and hypoxia‐activated hUCMSCs improves its therapeutic outcome

Abstract

Tissue engineering has brought new hopes for urethral reconstruction. However, the absence of pre-vascularization and the subsequent degradation of materials often lead to the failure of in vivo application. In this study, with the assistance of hypoxia-activated human umbilical cord mesenchymal stem cells (hUCMSCs), pedicled muscle flaps were used as materials and pre-incubated in ventral penile subcutaneous cavity of rabbit for 3 weeks to prepare a pre-vascularized urethral construct. We found that small vessels and muscle fibres were scattered in the construct after 3 weeks' pre-incubation. The construct presented a fibrous reticular structure, which was similar to that of the corpus spongiosum under microscope examination. The produced constructs were then used as a patch graft for reconstruction of the defective rabbit urethra (experimental group), natural muscular patch was used as control (control group). Twelve weeks after the reconstructive surgery, urethrography and urethroscope inspections showed wide calibres of the reconstructed urethra in the experimental group. Histopathological studies revealed that fibrous connective tissues and abundant muscle fibres constituted the main body of the patch-grafted urethra. In contrast, in the control group, only adipose tissue was found in the stenosis-reconstructed urethra, replacing the originally grafted muscular tissue. To our knowledge, this is the first report that successfully constructed a pre-vascularized urethral construct by using hypoxia-activated hUCMSC and pedicled muscle flaps. More importantly, the pre-vascularized construct showed a good performance in urethral reconstruction when applied in vivo. The study provided a novel strategy for tissue engineering of pre-vascularized urethral construct for the defective urethra, representing a further advancement in urethral reconstruction.

Regenerative potential of human dental pulp stem cells in the treatment of stress urinary incontinence: In vitro and in vivo study

“…57 Indeed, vascularization promotion is a well-documented ability characterizing hDPSCs 24,58,59 which does not relate to tumorigenesis, being instead important for regeneration. As formerly demonstrated by Sun et al, 60 vascularization proved to be a favourable condition in supporting the urethral regeneration. The regeneration of muscular component only would provide a transient/temporary recovery of the urinary continence.…”

Hypoxia Precondition Promotes Adipose-Derived Mesenchymal Stem Cells Based Repair of Diabetic Erectile Dysfunction via Augmenting Angiogenesis and Neuroprotection

“…To minimize the potential immune rejection in our study, AMSCs were derived from syngeneic rat donors, not human, but we could speculate that hypoxia pretreatment should produce similar effects on therapeutic function of human AMSCs for ED. Actually, several previous studies have investigated the influence of hypoxic pre-conditioning on therapeutic effects of human ADSCs in other animal model[ 53 , 54 ], and it has been confirmed that hypoxic pre-conditioning can improve the therapeutic effect of human ADSCs.…”

Plastic and Reconstructive Surgery in the Treatment of Oncological Perineal and Genital Defects

“…During the last years, important advances in generation of vascularized tissue engineering have been achieved ( 23 ). However, until today flap surgery still remains the gold standard for plastic-reconstructive treatment of oncological defects ( 24 ). The immediately/simultaneously used transpelvic VRAM flap has several advantages: first of all, the VRAM flap is a very safe and robust flap and relatively easy to technical perform, when necessary plastic-reconstructive expertise exists.…”