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

Abstract

Objectives To evaluate the regenerative potential of human dental pulp stem cells (hDPSCs) in an animal model of stress urinary incontinence (SUI). SUI, an involuntary leakage of urine, is due to physical stress involving an increase in bladder pressure and a damage of external urethral sphincter affecting muscles and nerves. Conventional therapies can only relieve the symptoms. Human DPSCs are characterized by peculiar stemness and immunomodulatory properties and might provide an alternative tool for SUI therapy. Materials and methods In vitro phase: hDPSCs were induced towards the myogenic commitment following a 24 hours pre‐conditioning with 5‐aza‐2′‐deoxycytidine (5‐Aza), then differentiation was evaluated. In vivo phase: pudendal nerve was transected in female rats to induce stress urinary incontinence; then, pre‐differentiated hDPSCs were injected in the striated urethral sphincter. Four weeks later, urethral sphincter regeneration was assayed through histological, functional and immunohistochemical analyses. Results Human DPSCs were able to commit towards myogenic lineage in vitro and, four weeks after cell injection, hDPSCs engrafted in the external urethral sphincter whose thickness was almost recovered, committed towards myogenic lineage in vivo, promoted vascularization and an appreciable recovery of the continence. Moreover, hDPSCs were detected within the nerve, suggesting their participation in repair of transected nerve. Conclusions These promising data and further investigations on immunomodulatory abilities of hDPSCs would allow to make them a potential tool for alternative therapies of SUI.

Epigenetic Regulation of Dental Pulp Stem Cell Fate

“…After being cultured in specific condition for several weeks, DPSCs elongate and display a myoblast-like phenotype. These DPSCs express specific myocytic immunohistochemical markers such as MyoD1, myosin, and MHC [ 79 , 80 ]. Other than the myogenic potential, DPSCs also preserve the capability to differentiate into adipocytes [ 81 , 82 ] and pancreatic cell lineage [ 83 , 84 ].…”

“…Moreover, DPSCs in prevascularized, scaffold-free, microtissue spheroids can successfully regenerate vascular dental pulp-like tissue, which provides a new strategy for endodontic treatment and makes dentin-pulp regeneration possible [ 85 ]. The clinical application potential of DPSCs is not only in dentistry but also in treatments for other diseases, such as craniofacial bone defects [ 86 ], muscle regeneration [ 87 ], myocardial infarction [ 88 ], Alzheimer's disease [ 89 ], nervous system injuries [ 90 ], Parkinson's disease, diabetes [ 91 ], stress urinary incontinence [ 80 ], osteoarthritis [ 92 ], and liver diseases [ 93 ].…”

Modulation of Cell Death and Promotion of Chondrogenic Differentiation by Fas/FasL in Human Dental Pulp Stem Cells (hDPSCs)

“…Following migration, neural crest cells generate the majority of craniofacial tissues, including tooth, fat, muscle, bone and cartilage tissues, as well as cranial peripheral ganglia and nerves, among other cell types, such as melanocytes (Pisciotta et al, 2020). It has been widely demonstrated that hDPSCs are able to differentiate toward lineages belonging to all the three germ layers, as a matter of fact these stem cells can commit to glial cells and participate in peripheral nerve regeneration (Carnevale et al, 2018), contribute in restoring urethral sphincter contractile function (Zordani et al, 2019), reduce fibrosis and ameliorate muscle trophism in Duchenne Muscular Dystrophy mouse model (Pisciotta et al, 2015b), besides promoting bone tissue regeneration in critical size calvarial defects (Pisciotta et al, 2012). Further evidence of the regenerative potential of hDPSCs is documented by their capability to promote vascularization in regenerating tissues in vivo and supported by their expression of VEGF (Laino et al, 2005).…”

A Role for Exosomes in Craniofacial Tissue Engineering and Regeneration

“…Either exfoliating deciduous teeth or intentionally harvested adult teeth can provide dental pulp stem cells (DPSCs) for regenerative purposes (Gronthos et al, 2000). DPSCs direct regeneration by in vivo multipotential differentiation, including liver, dental pulp, bone, muscle and nerve, besides promoting vascularization of the regenerating tissues (Gandia et al, 2008;Ikeda et al, 2008;Yamada et al, 2011;Bianchi et al, 2017;Zordani et al, 2019). DPSCs of neural crest derivation may provide particularly valuable function in nerve regeneration as demonstrated by their phentoype (Carnevale et al, 2018), their differentiation along neurogenic lineages and functional studies demonstrating DPSC-mediated functional regeneration of siatic nerve (Ullah et al, 2017).…”