Urine-derived stem cells(USCs)have shown potentials for the treatment of skeletal and urological disorders.Based on published literature and our own data,USCs consist of heterogeneous populations of cells.In this pape...Urine-derived stem cells(USCs)have shown potentials for the treatment of skeletal and urological disorders.Based on published literature and our own data,USCs consist of heterogeneous populations of cells.In this paper,we identify and characterize two morphologically distinct subpopulations of USCs from human urine samples,named as spindle-shaped USCs(SS-USCs)and rice-shaped USCs(RS-USCs)respectively.The two subpopulations showed similar clone-forming efficiency,while SS-USCs featured faster proliferation,higher motility,and greater potential for osteogenic and adipogenic differentiation,RS-USCs showed greater potential for chondrogenic differentiation.POU5F1 was strongly expressed in both subpopulations,but MYC was weakly expressed.Both subpopulations showed similar patterns of CD24,CD29,CD34,CD44,CD73,CD90 and CD105 expression,while a higher percentage of RS-USCs were positive for CD133.SS-USCs were positive for VIM,weakly positive for SLC12A1 and UMOD,and negative for KRT18,NPHS1,AQP1 and AQP2,indicating a renal mesenchyme origin;while RSUSCs are positive for VIM,partially positive for KRT18,NPHS1,AQP1,SLC12A1 and UMOD,and negative for AQP2,indicating a nephron tubule origin.The above results can facilitate understanding of the biological characteristics of subpopulations of USCs,and provide a basis for further research and applications of such cells.展开更多
Currently the standard surgical treatment for bladder defects is augmentation cystoplasty with autologous tissues,which has many side effects.Biomaterials such as small intestine submucosa(SIS)can provide an alternati...Currently the standard surgical treatment for bladder defects is augmentation cystoplasty with autologous tissues,which has many side effects.Biomaterials such as small intestine submucosa(SIS)can provide an alternative scaffold for the repair as bladder patches.Previous studies have shown that SIS could enhance the capacity and compliance of the bladder,but its application is hindered by issues like limited smooth muscle regeneration and stone formation since the fast degradation and poor mechanical properties of the SIS.Procyanidins(PC),a natural bio-crosslinking agent,has shown anti-calcification,anti-inflammatory and anti-oxidation properties.More importantly,PC and SIS can crosslink through hydrogen bonds,which may endow the material with enhanced mechanical property and stabilized functionalities.In this study,various concentrations of PC-crosslinked SIS(PC-SIS)were prepared to repair the full-thickness bladder defects,with an aim to reduce complications and enhance bladder functions.In vitro assays showed that the crosslinking has conferred the biomaterial with superior mechanical property and anti-calcification property,ability to promote smooth muscle cell adhesion and upregulate functional genes expression.Using a rabbit model with bladder defects,we demonstrated that the PC-SIS scaffold can rapidly promote in situ tissue regrowth and regeneration,in particular smooth muscle remodeling and improvement of urinary functions.The PC-SIS scaffold has therefore provided a promising material for the reconstruction of a functional bladder.展开更多
The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes.Biomaterials such as submucosa of small intestine(SIS)have been widel...The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes.Biomaterials such as submucosa of small intestine(SIS)have been widely used as patches for bladder repair,but the outcomes are not fully satisfactory.To capture stem cells in situ has been considered as a promising strategy to speed up the process of re-cellularization and functionalization.In this study,we have developed an anti-CD29 antibody-conjugated SIS scaffold(AC-SIS)which is capable of specifically capturing urine-derived stem cells(USCs)in situ for tissue repair and regeneration.The scaffold has exhibited effective capture capacity and sound biocompatibility.In vivo experiment proved that the AC-SIS scaffold could promote rapid endothelium healing and smooth muscle regeneration.The endogenous stem cell capturing scaffolds has thereby provided a new revenue for developing effective and safer bladder patches.展开更多
基金supported by the National Key Research&Development Program of China(2017YFC1104702)the National Natural Science Foundation of China(31771065,31600792,81473446)+1 种基金the Sichuan Science and Technology Program(2019JDRC0020)the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYJC18002)。
文摘Urine-derived stem cells(USCs)have shown potentials for the treatment of skeletal and urological disorders.Based on published literature and our own data,USCs consist of heterogeneous populations of cells.In this paper,we identify and characterize two morphologically distinct subpopulations of USCs from human urine samples,named as spindle-shaped USCs(SS-USCs)and rice-shaped USCs(RS-USCs)respectively.The two subpopulations showed similar clone-forming efficiency,while SS-USCs featured faster proliferation,higher motility,and greater potential for osteogenic and adipogenic differentiation,RS-USCs showed greater potential for chondrogenic differentiation.POU5F1 was strongly expressed in both subpopulations,but MYC was weakly expressed.Both subpopulations showed similar patterns of CD24,CD29,CD34,CD44,CD73,CD90 and CD105 expression,while a higher percentage of RS-USCs were positive for CD133.SS-USCs were positive for VIM,weakly positive for SLC12A1 and UMOD,and negative for KRT18,NPHS1,AQP1 and AQP2,indicating a renal mesenchyme origin;while RSUSCs are positive for VIM,partially positive for KRT18,NPHS1,AQP1,SLC12A1 and UMOD,and negative for AQP2,indicating a nephron tubule origin.The above results can facilitate understanding of the biological characteristics of subpopulations of USCs,and provide a basis for further research and applications of such cells.
基金This work was supported by the National Key R&D Program of China(No.2017YFC1104702)Sichuan Science and Technology Program(No.2019JDRC0020)1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYJC18002).
文摘Currently the standard surgical treatment for bladder defects is augmentation cystoplasty with autologous tissues,which has many side effects.Biomaterials such as small intestine submucosa(SIS)can provide an alternative scaffold for the repair as bladder patches.Previous studies have shown that SIS could enhance the capacity and compliance of the bladder,but its application is hindered by issues like limited smooth muscle regeneration and stone formation since the fast degradation and poor mechanical properties of the SIS.Procyanidins(PC),a natural bio-crosslinking agent,has shown anti-calcification,anti-inflammatory and anti-oxidation properties.More importantly,PC and SIS can crosslink through hydrogen bonds,which may endow the material with enhanced mechanical property and stabilized functionalities.In this study,various concentrations of PC-crosslinked SIS(PC-SIS)were prepared to repair the full-thickness bladder defects,with an aim to reduce complications and enhance bladder functions.In vitro assays showed that the crosslinking has conferred the biomaterial with superior mechanical property and anti-calcification property,ability to promote smooth muscle cell adhesion and upregulate functional genes expression.Using a rabbit model with bladder defects,we demonstrated that the PC-SIS scaffold can rapidly promote in situ tissue regrowth and regeneration,in particular smooth muscle remodeling and improvement of urinary functions.The PC-SIS scaffold has therefore provided a promising material for the reconstruction of a functional bladder.
基金supported by the National Natural Science Foundation of China(Grant No.32171351,31771065)National Key Research and Development Program of China(Grant No.2017YFC1104702)the“1.3.5”Project for Disciplines of Excellence,West China Hospital,Sichuan University(Grant No.ZYJC18002).
文摘The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes.Biomaterials such as submucosa of small intestine(SIS)have been widely used as patches for bladder repair,but the outcomes are not fully satisfactory.To capture stem cells in situ has been considered as a promising strategy to speed up the process of re-cellularization and functionalization.In this study,we have developed an anti-CD29 antibody-conjugated SIS scaffold(AC-SIS)which is capable of specifically capturing urine-derived stem cells(USCs)in situ for tissue repair and regeneration.The scaffold has exhibited effective capture capacity and sound biocompatibility.In vivo experiment proved that the AC-SIS scaffold could promote rapid endothelium healing and smooth muscle regeneration.The endogenous stem cell capturing scaffolds has thereby provided a new revenue for developing effective and safer bladder patches.