|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Mechanical integrin stress and magnetic forces induce biological responses in mesenchymal stem cells which depend on environmental factors. J Cell Biochem. 2010 Nov 4; Authors: Kasten A, Müller P, Bulnheim U, Groll J, Bruellhoff K, Beck U, Steinhoff G, Möller M, Rychly J The control of mesenchymal stem cells (MSC) by physical cues is of great interest in regenerative medicine. Because integrin receptors function as mechanotransducers, we applied drag forces to β1 integrins on the apical surface of adherent human MSC. In addition to mechanical forces, the technique we used involved also the exposure of the cells to a inhomogeneous magnetic field. In order to assess the influence of the substrate on cell adhesion, cells were cultured on plain tissue culture polystyrene (TCP) or on coated well plates which allowed only adhesion to embedded fibronectin or RGD peptides. We found that the expression of collagen I, which is involved in osteogenesis, and VEGF, a factor which stimulates angiogenesis, increased as a result of short-term mechanical integrin stress. Whereas collagen I expression was stimulated by mechanical forces when the cells were cultured on fibronectin and RGD peptides but not on TCP, VEGF expression was enhanced by physical stimulation on TCP. The study further revealed that magnetic forces enhanced Sox 9 expression, a marker of chondrogenesis, and reduced the expression of ALP. Concerning the intracellular mechanisms involved, we found that the expression of VEGF induced by physical forces depended on Akt activation. Together, the results implicate that biological functions of MSC can be stimulated by integrin-mediated mechanical forces and a magnetic field. However, the responses of cells depend strongly on the substrate to which they adhere and on the cross talk between integrin mediated signals and soluble factors. © 2010 Wiley-Liss, Inc. PMID: 21053275 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Early-acting hematopoietic growth factors: biology and clinical experience. Cancer Treat Res. 2011;157:11-31 Authors: Szilvassy SJ Secreted protein growth factors that stimulate the self-renewal, proliferation, and differentiation of the most primitive stem cells are among the most biologically interesting molecules and at least theoretically have diverse applications in the evolving field of regenerative medicine. Among this class of regulators, the early-acting hematopoietic growth factors and their cellular targets are perhaps the best characterized and serve as a paradigm for manipulating other stem cell based tissues. This chapter reviews the preclinical knowledge accumulated over ∼40 years, since the discovery of the first such growth factor, and the clinical applications of those that, upon testing in humans, ultimately gained regulatory approval for the treatment of various hematological diseases. PMID: 21052948 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Stem Cell Update: Highlights from the 2010 Lugano Stem Cell Meeting. J Cardiovasc Transl Res. 2010 Oct 30; Authors: Bardelli S, Astori G, Sürder D, Tallone T, Terzic A, Soldati G, Moccetti T The 2010 edition of the Lugano Stem Cell Meeting, under the auspices of the Swiss center of excellence in cardiovascular diseases "Cardiocentro Ticino" and the Swiss Stem Cell Foundation, offered an update on clinical, translational, and biotechnological advances in regenerative science and medicine pertinent to cardiovascular applications. Highlights from the international forum ranged from innate mechanisms of heart repair, safety, and efficacy of ongoing and completed clinical trials, novel generations of stem cell biologics, bioengineered platforms, and regulatory processes. In the emerging era of regenerative medicine, accelerating the critical path from discovery to product development will require integrated multidisciplinary teams to ensure timely translation of new knowledge into validated algorithms for practice adoption. PMID: 21052883 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The Stem Cell Niche Should be a Key Issue for Cell Therapy in Regenerative Medicine. Stem Cell Rev. 2010 Oct 30; Authors: Becerra J, Santos-Ruiz L, Andrades JA, Marí-Beffa M Recent advances in stem cell research have highlighted the role played by such cells and their environment (the stem cell niche) in tissue renewal and homeostasis. The control and regulation of stem cells and their niche are remaining challenges for cell therapy and regenerative medicine on several tissues and organs. These advances are important for both, the basic knowledge of stem cell regulation, and their practical translational applications into clinical medicine. This article is primarily concerned with the mesenchymal stem cells (MSCs) and it reviews the current aspects of their own niche. We discuss on the need for a deeper understanding of the identity of this cell type and its microenvironment in order to improve the effectiveness of any cell therapy for regenerative medicine. Ex vivo reproduction of the conditions of the natural stem cell niche, when necessary, would provide success to tissue engineering. The first challenge of regenerative medicine is to find cells able to replace and/or repair the lost function of tissues and organs by disease or aging and the trophic and immunomodulatory effects recently found for MSCs open up for new opportunities. If MSCs are pericytes, as it has been proposed, perhaps it may explain the ubiquity of these cells and their possible role in miscellaneous repairs throughout the body opening for new chances for extensive tissue repair. PMID: 21052872 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Lateral flow nucleic acid biosensor for Cu(2+) detection in aqueous solution with high sensitivity and selectivity. Chem Commun (Camb). 2010 Nov 4; Authors: Fang Z, Huang J, Lie P, Xiao Z, Ouyang C, Wu Q, Wu Y, Liu G, Zeng L A lateral flow nucleic acid biosensor based on copper-dependent DNA-cleaving DNAzyme and gold nanoparticles has been developed for the visual detection of copper ions (Cu(2+)) in an aqueous solution with a detection limit of 10 nM. PMID: 21052572 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The autophagic tumor stroma model of cancer or "battery-operated tumor growth": A simple solution to the autophagy paradox. Cell Cycle. 2010 Nov 30;9(21) Authors: Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, Chiavarina B, Bonuccelli G, Trimmer C, Tsirigos A, Migneco G, Witkiewicz AK, Balliet R, Mercier I, Wang C, Flomenberg N, Howell A, Lin Z, Caro J, Pestell RG, Sotgia F, Lisanti MP The role of autophagy in tumorigenesis is controversial. Both autophagy inhibitors (chloroquine) and autophagy promoters (rapamycin) block tumorigenesis by unknown mechanism(s). This is called the "Autophagy Paradox". we have recently reported a simple solution to this paradox. we demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building blocks by anabolic epithelial cancer cells. This model results in a net energy transfer from the tumor stroma to epithelial cancer cells (an energy imbalance), thereby promoting tumor growth. This net energy transfer is both unilateral and vectorial, from the tumor stroma to the epithelial cancer cells, representing a true host-parasite relationship. we have termed this new paradigm "The Autophagic Tumor Stroma Model of Cancer Cell Metabolism" or "Battery-Operated Tumor Growth". In this sense, autophagy in the tumor stroma serves as a "battery" to fuel tumor growth, progression and metastasis, independently of angiogenesis. Using this model, the systemic induction of autophagy will prevent epithelial cancer cells from using recycled nutrients, while the systemic inhibiton of autophagy will prevent stromal cells from producing recycled nutrients-both effectively "starving" cancer cells. We discuss the idea that tumor cells could become resistant to the systemic induction of autophagy, by the upregulation of natural endogenous autophagy inhibitors in cancer cells. Alternatively, tumor cells could also become resistant to the systemic induction of autophagy, by the genetic silencing/deletion of pro-autophagic molecules, such as Beclin1. If autophagy resistance develops in cancer cells, then the systemic inhibition of autophagy would provide a therapeutic solution to this type of drug resistance, as it would still target autophagy in the tumor stroma. As such, an anti-cancer therapy that combines the alternating use of both autophagy promoters and autophagy inhibitors would be expected to prevent the onset of drug resistance. We also discuss why anti-angiogenic therapy has been found to promote tumor recurrence, progression and metastasis. More specifically, anti-angiogenic therapy would induce autophagy in the tumor stroma via the induction of stromal hypoxia, thereby converting a non-aggressive tumor type to a "lethal" aggressive tumor phenotype. Thus, uncoupling the metabolic parasitic relationship between cancer cells and an autophagic tumor stroma may hold great promise for anti-cancer therapy. Finally, we believe that autophagy in the tumor stroma is the local microscopic counterpart of systemic wasting (cancer-associated cachexia), which is associated with advanced and metastatic cancers. Cachexia in cancer patients is not due to decreased energy intake, but instead involves an increased basal metabolic rate and increased energy expenditures, resulting in a negative energy balance. Importantly, when tumors were surgically excised, this increased metabolic rate returned to normal levels. This view of cachexia, resulting in energy transfer to the tumor, is consistent with our hypothesis. So, cancer-associated cachexia may start locally as stromal autophagy, and then spread systemically. As such, stromal autophagy may be the requisite precursor of systemic cancer-associated cachexia. PMID: 21051947 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Periurethral Injection of Autologous Adipose-Derived Stem Cells with Controlled-Release Nerve Growth Factor for the Treatment of Stress Urinary Incontinence in a Rat Model. Eur Urol. 2010 Oct 26; Authors: Zhao W, Zhang C, Jin C, Zhang Z, Kong D, Xu W, Xiu Y BACKGROUND: Stem cell therapy is a promising therapeutic strategy for stress urinary incontinence (SUI). However, its current efficacy is insufficient. OBJECTIVE: We designed a stem cell transplantation system that contains autologous adipose-derived stem cells (ADSC) and controlled-release nerve growth factor (NGF). We evaluated whether this system could enhance the therapeutic efficacy of ADSCs by periurethral coinjection in SUI rats. DESIGN, SETTING, AND PARTICIPANTS: We first tested for the presence of NGF receptors in rat ADSCs and observed the effect of NGF on ADSCs in vitro and in vivo. NGF was encapsulated within poly(lactic-co-glycolic acid-PLGA) microspheres (PLGA/NGF) to control its release. SUI was created in rats, and ADSCs were harvested, cultured from fat tissue, and retained for later transplantation. SUI rats then received different forms of periurethral injection therapy. Their urodynamic index was monitored. Eight weeks after injection, the SUI rats were sacrificed and their urethra removed for histologic evaluation. INTERVENTION: Forty SUI rats were allocated to five groups for receiving periurethral injection with phosphate-buffered saline (PBS), ADSC, ADSC+PLGA, ADSC+NGF, or ADSC+PLGA/NGF. Bladder capacities, abdominal leak point pressure (ALPP), and retrograde urethral perfusion pressure (RUPP) were reassessed at 2, 6, and 8 wk after injection. MEASUREMENTS: The rat SUI model was generated by bilateral pudendal nerve transection (PNT). Real-time polymerase chain reaction (RT-PCR) and western blotting detected the NGF receptor Ark-A. The regeneration of muscles and peripheral nerves was evaluated by Masson's trichrome and immunohistochemical staining. RESULTS AND LIMITATIONS: Results revealed the presence of the NGF receptor Trk-A on rat ADSCs. Short-term observations showed that NGF could improve ADSCs' viability in vitro and in vivo. ADSCs delivered intramuscularly into the urethra in combination with PLGA/NGF resulted in significant improvements in ALPP and RUPP as well as the amount of muscle and ganglia. There was a significant difference between the ADSC+PLGA/NGF group and other groups. CONCLUSIONS: Periurethral coinjection of autologous ADSCs with controlled-release NGF may be a potential strategy for SUI treatment. PMID: 21050657 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | REVIEW: Stem Cell Therapy in Cardiovascular Disorders. Cardiovasc Ther. 2010 Oct;28(5):e101-10 Authors: Krause K, Schneider C, Kuck KH, Jaquet K Heart insufficiency remains the leading cause of death despite pharmacological and interventional therapy as well as primary and secondary prevention. Laboratory research on cardiac repair implementing stem cells and progenitor cells has raised great expectations as well as controversies. The potential of diverse progenitor cells to repair damaged heart tissue includes replacement (tissue transplant), restoration (activation of resident cardiac progenitor cells, paracrine effects), and regeneration (stem cell engraftment forming new myocytes). Based on promising experimental results clinical trials including several hundreds of patients with ischemic heart disease have been initiated using mostly bone marrow-derived cells. Probably, due to a lack of standardization of cell isolation and delivery methods these trials showed controverse results regarding effectiveness. However, significant therapeutic regeneration of human myocardium could not be proven until now. Several issues are at debate concerning the translation of the experimental data into the clinic discussing the adequate cell type, dosing, timing, and delivery mode of myocardial stem cell therapy. This review focusses on the potential and clinical translation of cell based therapies in cardiovascular disease. PMID: 21050418 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | In vitro and in vivo biocompatibility studies of a recombinant analogue of spidroin 1 scaffolds. J Biomed Mater Res A. 2010 Nov 4; Authors: Moisenovich MM, Pustovalova OL, Yu Arhipova A, Vasiljeva TV, Sokolova OS, Bogush VG, Debabov VG, Sevastianov VI, Kirpichnikov MP, Agapov II The goal of this study was to generate porous scaffolds from the genetically engineered protein, an analogue of Nephila clavipes spidroin 1 (rS1/9) and to assess the properties of new rS1/9 scaffolds essential for bioengineering. The salt leaching technique was used to make the rS1/9 scaffolds of interconnected macroporous structure with spontaneously formed micropores. The tensile strength of scaffolds was 18 ± 5 N/cm(2). Scaffolds were relatively stable in a phosphate buffer but degraded in oxidizing environment after 11 weeks of incubation. Applicability of the recombinant spidroin 1 as a substrate for cell culture was demonstrated by successful 3T3 cells growth on the surface of rS1/9 films (270 ± 20 cells/mm(2) vs. 97 ± 8 cells/mm(2) on the glass surface, p < 0.01). The 3T3 fibroblasts readily proliferated within the rS1/9 scaffold (from initially plated 19 ± 2 cells/mm(3) to 3800 ± 304 cells/mm(3) after 2 weeks). By this time, cells were uniformly distributed between the surface and deeper layers (27% ± 8% and 33% ± 4%, respectively; p > 0.05), whereas the initial distribution was 58% ± 7% and 11% ± 8%, respectively; p < 0.05). The rS1/9 scaffolds implanted subcutaneously into Balb/c mice were well tolerated. Over a 2-month period, the scaffolds promoted an ingrowth of de novo formed vascularized connective tissue elements and nerve fibers. Thus, scaffolds made of the novel recombinant spidroin 1 analogue are potentially applicable in tissue engineering. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 21053270 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The Stem Cell Niche Should be a Key Issue for Cell Therapy in Regenerative Medicine. Stem Cell Rev. 2010 Oct 30; Authors: Becerra J, Santos-Ruiz L, Andrades JA, Marí-Beffa M Recent advances in stem cell research have highlighted the role played by such cells and their environment (the stem cell niche) in tissue renewal and homeostasis. The control and regulation of stem cells and their niche are remaining challenges for cell therapy and regenerative medicine on several tissues and organs. These advances are important for both, the basic knowledge of stem cell regulation, and their practical translational applications into clinical medicine. This article is primarily concerned with the mesenchymal stem cells (MSCs) and it reviews the current aspects of their own niche. We discuss on the need for a deeper understanding of the identity of this cell type and its microenvironment in order to improve the effectiveness of any cell therapy for regenerative medicine. Ex vivo reproduction of the conditions of the natural stem cell niche, when necessary, would provide success to tissue engineering. The first challenge of regenerative medicine is to find cells able to replace and/or repair the lost function of tissues and organs by disease or aging and the trophic and immunomodulatory effects recently found for MSCs open up for new opportunities. If MSCs are pericytes, as it has been proposed, perhaps it may explain the ubiquity of these cells and their possible role in miscellaneous repairs throughout the body opening for new chances for extensive tissue repair. PMID: 21052872 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Heparin-functionalized collagen matrices with controlled release of basic fibroblast growth factor. J Mater Sci Mater Med. 2010 Nov 4; Authors: Wu JM, Xu YY, Li ZH, Yuan XY, Wang PF, Zhang XZ, Liu YQ, Guan J, Guo Y, Li RX, Zhang H Tissue engineering scaffolds with controlled long-term release of growth factors are constructed in an attempt to mimic the intelligent ability of the extracellular matrix (ECM) to release endogenous growth factors. In this study, collagen sponges (Collagen group) were modified by N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) crosslinking (EDC/NHS group) and heparin immobilization (EDC/NHS-H group), and subsequently seeded with human umbilical vein endothelial cells (HUVECs). Native and modified sponges were pre-adsorbed with basic fibroblast growth factor (bFGF) to evaluate the sustained release and bioactive maintenance of bFGF from the sponges. We found that modified collagen matrices permitted HUVECs to proliferate and migrate well and to distribute uniformly. The EDC/NHS-H group exhibited an excellent sustained-release profile and bioactive maintenance of the pre-adsorbed bFGF as compared with the Collagen and EDC/NHS groups. These results suggest that heparin-functionalized collagen matrices can support a controlled release of bFGF and thus, have potential as a tissue engineering scaffold. PMID: 21052795 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effects of different cross-linking conditions on the properties of genipin-cross-linked chitosan/collagen scaffolds for cartilage tissue engineering. J Mater Sci Mater Med. 2010 Nov 5; Authors: Bi L, Cao Z, Hu Y, Song Y, Yu L, Yang B, Mu J, Huang Z, Han Y A cross-linking reagent is required to improve mechanical strength and degradation properties of biopolymers for tissue engineering. To find the optimal preparative method, we prepared diverse genipin-cross-linked chitosan/collagen scaffolds using different genipin concentrations and various cross-linking temperatures and cross-linking times. The compressive strength increased with the increasing of genipin concentration from 0.1 to 1.0%, but when concentration exceeded 1.0%, the compressive strength decreased. Similarly, the compressive strength increased with the increasing of temperature from 4 to 20°C, but when temperature reached 37°C, the compressive strength decreased. Showing a different trend from the above two factors, the effect of cross-linking time on the compressive strength had a single increasing tendency. The other results also demonstrated that the pore size, degradation rate and swelling ratio changed significantly with different cross-linking conditions. Based on our study, 1.0% genipin concentration, 20°C cross-linking temperature and longer cross-linking time are recommended. PMID: 21052794 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | An overview of methods for the in vivo evaluation of tissue-engineered skin constructs. Tissue Eng Part B Rev. 2010 Nov 5; Authors: Lammers G, Verhaegen PD, Ulrich MM, Schalkwijk J, Middelkoop E, Weiland D, Nillesen ST, van Kuppevelt TH, Daamen WF Cutaneous wounding often leads to contraction and scarring, which may result in a range of functional, cosmetic and psychological complications. Tissue-engineered skin substitutes are being developed to enhance restoration of the skin and improve the quality of wound healing. The aim of this review is to provide researchers in the field of tissue engineering an overview of the methods that are currently used to clinically evaluate skin wound healing, and methods that are used to evaluate tissue engineered constructs in animal models. Clinically, the quality of wound healing is assessed by non-invasive subjective scar assessment scales and objective techniques to measure individual scar features. Alternatively, invasive technologies are used. In animal models, most tissue-engineered skin constructs studied are at least evaluated macroscopically and by using conventional histology (H&E staining). Planimetry and immunohistochemistry are also often applied. An overview of antibodies used is provided. In addition, some studies used methods to assess gene expression levels and mRNA location, transillumination for blood vessel visualisation, in situ/in vivo imaging, electron microscopy, mechanical strength assessment, animal behaviour analysis and microbiological sampling. A more systematic evaluation of tissue-engineered skin constructs in animal models is recommended to enhance the comparison of different constructs, thereby accelerating the trajectory to application in human patients. This would be further enhanced by the embracement of more clinically relevant objective evaluation methods. In addition, fundamental knowledge on construct-mediated wound healing may be increased by new developments in e.g. gene expression analysis and non-invasive imaging. PMID: 21050145 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Synthesis and Electrospinning of ε-Polycaprolactone-Bioactive Glass Hybrid Biomaterials via a Sol-Gel Process. Langmuir. 2010 Nov 4; Authors: Allo BA, Rizkalla AS, Mequanint K Strategies of bone tissue engineering and regeneration rely on bioactive scaffolds to mimic the natural extracellular matrix (ECM) as templates onto which cells attach, multiply, migrate, and function. For this purpose, hybrid biomaterials based on smart combinations of biodegradable polymers and bioactive glasses (BGs) are of particular interest, since they exhibit tailored physical, biological, and mechanical properties, as well as predictable degradation behavior. In this study, hybrid biomaterials with different organic-inorganic ratios were successfully synthesized via a sol-gel process. Poly(ε-caprolactone) (PCL) and tertiary bioactive glass (BG) with a glass composition of 70 mol % SiO(2), 26 mol % CaO, and 4 mol % of P(2)O(5) were used as the polymer and inorganic phases, respectively. The polymer chains were successfully introduced into the inorganic sol while the networks were formed. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analyses (TGA), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX) were used to investigate the presence of different chemical groups, structural crystallinity, thermal property, elemental composition, and homogeneity of the synthesized hybrid biomaterials. Identification of chemical groups and the presence of molecular interaction by hydrogen bonding between the organic and inorganic phases was confirmed by FTIR. The XRD patterns showed that all PCL/BG hybrids (up to 60% polymer content) were amorphous. The TGA study revealed that the PCL/BG hybrid biomaterials were thermally stable, and good agreement was observed between the experimental and theoretical organic-inorganic ratios. The SEM/EDX results also revealed a homogeneous elemental distribution and demonstrated the successful incorporation of all the elements in the hybrid system. Finally, these synthesized hybrid biomaterials were successfully electrospun into 3D scaffolds. The resultant fibers have potential use as scaffolds for bone regeneration. PMID: 21050002 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Simple and Biocompatible Micropatterning of Multiple Cell Types on a Polymer Substrate by Using Ion Implantation. Langmuir. 2010 Nov 4; Authors: Hwang IT, Jung CH, Choi JH, Nho YC A noncytotoxic procedure for the spatial organization of multiple cell types remains as a major challenge in tissue engineering. In this study, a simple and biocompatible micropatterning method of multiple cell types on a polymer surface is developed by using ion implantation. The cell-resistant Pluronic surface can be converted into a cell-adhesive one by ion implantation. In addition, cells show different behaviors on the ion-implanted Pluronic surface. Thus this process enables the micropatterning of two different cell types on a polymer substrate. The micropatterns of the Pluronic were formed on a polystyrene surface. Primary cells adhered to the spaces of the bare polystyrene regions separated by the implanted Pluronic patterns. Secondary cells then adhered onto the implanted Pluronic patterns, resulting in micropatterns of two different cells on the polystyrene surface. PMID: 21049964 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | What's new in orthopaedic research. J Bone Joint Surg Am. 2010 Oct;92(14):2491-501 Authors: Rodeo SA, Delos D, Weber A, Ju X, Cunningham ME, Fortier L, Maher S PMID: 20962201 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Periurethral Injection of Autologous Adipose-Derived Stem Cells with Controlled-Release Nerve Growth Factor for the Treatment of Stress Urinary Incontinence in a Rat Model. Eur Urol. 2010 Oct 26; Authors: Zhao W, Zhang C, Jin C, Zhang Z, Kong D, Xu W, Xiu Y BACKGROUND: Stem cell therapy is a promising therapeutic strategy for stress urinary incontinence (SUI). However, its current efficacy is insufficient. OBJECTIVE: We designed a stem cell transplantation system that contains autologous adipose-derived stem cells (ADSC) and controlled-release nerve growth factor (NGF). We evaluated whether this system could enhance the therapeutic efficacy of ADSCs by periurethral coinjection in SUI rats. DESIGN, SETTING, AND PARTICIPANTS: We first tested for the presence of NGF receptors in rat ADSCs and observed the effect of NGF on ADSCs in vitro and in vivo. NGF was encapsulated within poly(lactic-co-glycolic acid-PLGA) microspheres (PLGA/NGF) to control its release. SUI was created in rats, and ADSCs were harvested, cultured from fat tissue, and retained for later transplantation. SUI rats then received different forms of periurethral injection therapy. Their urodynamic index was monitored. Eight weeks after injection, the SUI rats were sacrificed and their urethra removed for histologic evaluation. INTERVENTION: Forty SUI rats were allocated to five groups for receiving periurethral injection with phosphate-buffered saline (PBS), ADSC, ADSC+PLGA, ADSC+NGF, or ADSC+PLGA/NGF. Bladder capacities, abdominal leak point pressure (ALPP), and retrograde urethral perfusion pressure (RUPP) were reassessed at 2, 6, and 8 wk after injection. MEASUREMENTS: The rat SUI model was generated by bilateral pudendal nerve transection (PNT). Real-time polymerase chain reaction (RT-PCR) and western blotting detected the NGF receptor Ark-A. The regeneration of muscles and peripheral nerves was evaluated by Masson's trichrome and immunohistochemical staining. RESULTS AND LIMITATIONS: Results revealed the presence of the NGF receptor Trk-A on rat ADSCs. Short-term observations showed that NGF could improve ADSCs' viability in vitro and in vivo. ADSCs delivered intramuscularly into the urethra in combination with PLGA/NGF resulted in significant improvements in ALPP and RUPP as well as the amount of muscle and ganglia. There was a significant difference between the ADSC+PLGA/NGF group and other groups. CONCLUSIONS: Periurethral coinjection of autologous ADSCs with controlled-release NGF may be a potential strategy for SUI treatment. PMID: 21050657 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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