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Human urine-derived stem cells seeded in a modified 3D porous small intestinal submucosa scaffold for urethral tissue engineering

Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Biomaterials (Impact Factor: 8.31). 11/2010; 32(5):1317-26. DOI: 10.1016/j.biomaterials.2010.10.006
Source: PubMed

ABSTRACT The goal of this study was to determine whether urothelial cells (UC) and smooth muscle cells (SMC) derived from the differentiation of urine-derived stem cells (USC) could be used to form engineered urethral tissue when seeded on a modified 3-D porous small intestinal submucosa (SIS) scaffold. Cells were obtained from 12 voided urine samples from 4 healthy individuals. USC were isolated, characterized and induced to differentiate into UC and SMC. Fresh SIS derived from pigs was decellularized with 5% peracetic acid (PAA). Differentiated UC and SMC derived from USC were seeded onto SIS scaffolds with highly porous microstructure in a layered co-culture fashion and cultured under dynamic conditions for one week. The seeded cells formed multiple uniform layers on the SIS and penetrated deeper into the porous matrix during dynamic culture. USC that were induced to differentiate also expressed UC markers (Uroplakin-III and AE1/AE3) or SMC markers (α-SM actin, desmin, and myosin) after implantation into athymic mice for one month, and the resulting tissues were similar to those formed when UC and SMC derived from native ureter were used. In conclusion, UC and SMC derived from USC could be maintained on 3-D porous SIS scaffold. The dynamic culture system promoted 3-D cell-matrix ingrowth and development of a multilayer mucosal structure similar to that of native urinary tract tissue. USC may serve as an alternative cell source in cell-based tissue engineering for urethral reconstruction or other urological tissue repair.

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    • "Cells differentiated from USCs were seeded on a modified 3D porous small intestinal submucosa in order to form engineered urethral tissue. Results showed that the cells formed multiple uniform layers on the scaffolds, which was similar to that of native urinary tract tissue [5]. As USCs can be obtained using non-invasive and simple methods, they represent a promising alternative stem cell population for tissue regeneration. "
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    ABSTRACT: Human urine-derived stem cells (USCs) have great application potential for cytotherapy as they can be obtained by non-invasive and simple methods. Silicate bioceramics, including calcium silicate (CS), can stimulate osteogenic differentiation of stem cells. However, the effects of silicate bioceramics on osteogenic differentiation of USCs have not been reported. In this study, at first, we investigated the effects of CS ion extracts on proliferation and osteogenic differentiation of USCs, as well as the related mechanism. CS particles were incorporated into poly (lactic-co-glycolic acid) (PLGA) to obtain PLGA/CS composite scaffolds. USCs were then seeded onto these scaffolds, which were subsequently transplanted into nude mice to analyze the osteogenic differentiation of USCs and mineralization of extracellular matrix formed by USCs in vivo. The results showed that CS ion extracts significantly enhanced cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition, and expression of certain osteoblast-related genes and proteins. In addition, cardamonin, a Wnt/β-catenin signaling inhibitor, reduced the stimulatory effects of CS ion extracts on osteogenic differentiation of USCs, indicating that the observed osteogenic differentiation of USCs induced by CS ion extracts involves Wnt/β-catenin signaling pathway. Furthermore, histological analysis showed that PLGA/CS composite scaffolds significantly enhanced the osteogenic differentiation of USCs in vivo. Taken together, these results suggest the therapeutic potential of combining USCs and PLGA/CS scaffolds in bone tissue regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Biomaterials 07/2015; 55. DOI:10.1016/j.biomaterials.2015.03.029 · 8.31 Impact Factor
    • "These cells were able to differentiate into smooth muscle and urothelial cells in vitro, and after seeding on bacterial cellulose scaffold, were used to create model of urinary conduit [34]. One year later, this same method, using 3-D porous SIS scaffold , was used for experimental urethra construction [32]. Due to its ability to differentiate into urothelial lineages, USCs are an ideal cell source for the regeneration of other urinary tract components like the bladder, or the ureters [20] [66]. "
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    ABSTRACT: In recent years, urine has emerged as a source of urine cells. Two different types of cells can be isolated from urine: urine derived stem cells (USCs) and renal tubular cells called urine cells (UCs). USCs have great differentiation properties and can be potentially used in genitourinary tract regeneration. Within this paper, we attempt to demonstrate that such as easily accessible source of cells, collected during completely non-invasive procedures, can be better utilized. Cells derived from urine can be isolated, stored, and used for the creation of urine stem cell banks. In the future, urine holds great potential to become a main source of cells for tissue engineering and regenerative medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Medical Hypotheses 01/2015; 84(4). DOI:10.1016/j.mehy.2015.01.019 · 1.07 Impact Factor
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    • "To facilitate the effective regrowth of the smooth muscle layers, the seeding of cells on biodegradable scaffolds has demonstrated a beneficial impact on the remodelling of the bladder (Chung et al., 2005; Frimberger et al., 2005; Lu et al., 2005; Shukla et al., 2008; Wu et al., 2011; Zhang et al., 2004, 2005) and gastrointestinal tract (Araki et al., 2009; Hori et al., 2002; Nakase et al., 2006; Qin and Dunn, 2011). Recently, several studies have demonstrated the successful regeneration of bladder defects in animals using SIS grafts seeded with cells such as human embryonic germ cell-derived cells (Frimberger et al., 2005), muscle-derived cells (Lu et al., 2005; Zhang et al., 2004), urine-derived stem cells (Wu et al., 2011) or bone marrow stromal cells (Chung et al., 2005; Shukla et al., 2008; Zhang et al., 2005). Because other researchers have successfully used SIS grafts seeded with various types of stem/progenitor cells to regenerate bladder defects, in the present study we developed a novel stomach tissue-engineering approach using commercialized SIS seeded with bone marrowderived mesenchymal stem cells (MSCs) as the cell source. "
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    ABSTRACT: Small intestinal submucosa (SIS) is a biodegradable collagen-rich matrix containing functional growth factors. We have previously reported encouraging outcomes for regeneration of an artificial defect in the rodent stomach using SIS grafts, although the muscular layer was diminutive. In this study, we investigated the feasibility of SIS in conjunction with mesenchymal stem cells (MSCs) for regeneration of the gastrointestinal tract. MSCs from the bone marrow of green fluorescence protein (GFP)-transgenic Sprague-Dawley (SD) rats were isolated and expanded ex vivo. A 1 cm whole-layer stomach defect in SD rats was repaired using: a plain SIS graft without MSCs (group 1, control); a plain SIS graft followed by intravenous injection of MSCs (group 2); a SIS graft co-cultured with MSCs (group 3); or a SIS sandwich containing an MSC sheet (group 4). Pharmacological, electrophysiological and immunohistochemical examination was performed to evaluate the regenerated stomach tissue. Contractility in response to a muscarinic receptor agonist, a nitric oxide precursor or electrical field stimulation was observed in all groups. SIS grafts seeded with MSCs (groups 3 and 4) appeared to support improved regeneration compared with SIS grafts not seeded with MSCs (groups 1 and 2), by enabling the development of well-structured smooth muscle layers of significantly increased length. GFP expression was detected in the regenerated interstitial tissue, with fibroblast-like cells in the seeded-SIS groups. SIS potently induced pharmacological and electrophysiological regeneration of the digestive tract, and seeded MSCs provided an enriched environment that supported tissue regeneration by the SIS graft in the engineered stomach. © 2013 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.
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