Transplantation of bone marrow-derived mesenchymal stem cells expressing elastin alleviates pelvic floor dysfunction

Abstract

BackgroundPelvic floor dysfunction (PFD) is a group of clinical conditions including stress urinary incontinence (SUI) and pelvic organ prolapse (POP). The abnormality of collagen and elastin metabolism in pelvic connective tissues is implicated in SUI and POP.MethodsTo reconstitute the connective tissues with normal distribution of collagen and elastin, we transduced elastin to bone marrow-derived mesenchymal stem cells (BMSC). Elastin-expressing BMSCs were then differentiated to fibroblasts using bFGF, which produced collagen and elastin. To achieve the sustained release of bFGF, we formulated bFGF in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP).ResultsIn an in vitro cell culture system of 7 days, when no additional bFGF was administrated, the initial PLGA-loaded bFGF NP induced prolonged production of collagen and elastin from elastin-expressing BMSCs. In vivo, co-injection of PLGA-loaded bFGF NP and elastin-expressing BMSCs into the PFD rats significantly improved the outcome of urodynamic tests. Together, these results provided an efficient model of connective tissue engineering using BMSC and injectable PLGA-loaded growth factors.ConclusionsOur results provided the first instance of a multidisciplinary approach, combining both stem cell and nanoparticle technologies, for the treatment of PFD.

TGF-β1 is Involved in Vitamin D-Induced Chondrogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells by Regulating the ERK/JNK Pathway

“…Bone marrow-derived mesenchymal stem cells (BMSCs) possess pluripotency during several passages, and are commonly acceptable for differentiation into many cell types, such as chondrocytes and osteoblasts [9-11]. Transplantation of BMSCs has been widely studied as promising treatments for ischemia-induced pulmonary injury [12], pelvic floor dysfunction [13] and olfactory disorder [14]. In terms of orthopaedic researches, BMSCs are proved to facilitate cartilage regeneration because of the rapid cell proliferation, multipotency and easy isolation [15].…”

MicroRNA-29 facilitates transplantation of bone marrow-derived mesenchymal stem cells to alleviate pelvic floor dysfunction by repressing elastin

“…In our previous work [12], we have demonstrated the effectiveness of the bFGF-loaded PLGA NPs in sustaining continuous proliferation of BMSCs in prolonged culture as the bFGF source. Similarly, we verified the in vitro curve of bFGF release, by incubating the bFGF-loaded PLGA NPs in the culture media for 7 days (Fig.…”

“…In our previous proof-of-concept study, we pioneered in a multidisciplinary therapy, involving an elastin gene modification, stem cells, and nanoparticle technology, and demonstrated its efficacy in the repair and regeneration of pelvic floor tissues in PFD rats [12]. In this current work, we have further expanded the scope of the therapeutic concept, to explore other potential regulatory factors, such as microRNAs (miRNAs or miRs).…”

“…The rat vaginal distention model was established as previously described [12]. Briefly, an 18F catheter was inserted into the rat vagina and then fixed with a single 3-0 silk suture.…”

“…Therefore reconstitution of the connective tissue with the right elastin distribution could be beneficial in alleviating defects in pelvic support. In a recent study, we have demonstrated the efficacy of elastin-expressing BMSC transplant in alleviating PFD symptoms in a rat model [12]. We first genetically engineered BMSCs to stably express and secrete elastin.…”