Esophageal tissue engineering:A new approach for esophageal replacement

A number of congenital and acquired disorders require esophageal tissue replacement.Various surgical techniques,such as gastric and colonic interposition,are standards of treatment,but frequently complicated by stenosis and other problems.Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function.We review the literature of esophageal tissue engineering,discuss its implications,compare the methodologies that have been employed and suggest possible directions for the future.Medline,Embase,the Cochrane Library,National Research Register and ClinicalTrials.gov databases were searched with the following search terms:stem cell and esophagus,esophageal replacement,esophageal tissue engineering,esophageal substitution.Reference lists of papers identified were also examined and experts in this field contacted for further information.All full-text articles in English of all potentially relevant abstracts were reviewed.Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation.When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality.Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration,whilst omental wrapping to induce vascularization of the construct has an uncertain benefit.Decellularized matrices have been recently suggested as the optimal choice for scaffolds,but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution.Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement.Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus.Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease,important barriers remain that need to be addressed.

Development of stem cell-based therapy for Parkinson’s disease

Parkinson’s disease(PD)is one of the most common neurodegenerative disorders of aging,characterized by the degeneration of dopamine neurons(DA neurons)in the substantial nigra,leading to the advent of both motor symptoms and non-motor symptoms.Current treatments include electrical stimulation of the affected brain areas and dopamine replacement therapy.Even though both categories are effective in treating PD patients,the disease progression cannot be stopped.The research advance into cell therapies provides exciting potential for the treatment of PD.Current cell sources include neural stem cells(NSCs)from fetal brain tissues,human embryonic stem cells(hESCs),induced pluripotent stem cells(iPSCs)and directly induced dopamine neurons(iDA neurons).Here,we evaluate the research progress in different cell sources with a focus on using iPSCs as a valuable source and propose key challenges for developing cells suitable for large-scale clinical applications in the treatment of PD.

Differentiated cells derived from fetal neural stem cells improve motor deficits in a rat model of Parkinson's disease

Objective: Parkinson's disease(PD), which is one of the most common neuro‐degenerative disorders, is characterized by the loss of dopamine(DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells(NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods: NSCs were isolated from 14‐week‐old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers: βⅢ‐tubulin and microtubule‐associated protein 2(neurons), tyrosine hydroxylase(DA neurons), and glial fibrillary acidic protein(glial cells). After a 6‐hydroxydopamine(6‐OHDA)‐lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6‐OHDA‐lesioned PD rats. Results: The motor behaviors of the PD rats were assessed by the number of apomorphine‐induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine‐induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions: Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.

Continuous live imaging reveals a subtle pathological alteration with cell behaviors in congenital heart malformation

To form fully functional four-chambered structure,mammalian heart development undergoes a transient finger-shaped trabeculae,crucial for efficient contraction and exchange for gas and nutrient.Although its developmental origin and direct relevance to congenital heart disease has been studied extensively,the time-resolved cellular mechanism underlying hypotrabeculation remains elusive.Here,we employed in toto live imaging and reconstructed the holistic cell lineages and cellular behavior landscape of control and hypotrabeculed hearts of mouse embryos from E9.5 for up to 24 h.Compared to control,hypotrabeculation in ErbB2 mutants arose mainly through dual mechanisms:both reduced proliferation of trabecular cardiomyocytes from early cell fate segregation and markedly impaired oriented cell division and migration.Further examination of mosaic mutant hearts confirmed alterations in cellular behaviors in a cell autonomous manner.Thus,our work offers a framework for continuous live imaging and digital cell lineage analysis to better understand subtle pathological alterations in congenital heart disease.

表面等离激元共振成像技术在识别和确认诱导多能干细胞生物标记中的应用(英文)

诱导多能干细胞(i PSCs)是再生医学领域,尤其是细胞治疗和药物筛选研究中非常有吸引力的细胞来源.然而,再生医学需要对i PSCs进行快速、精准鉴别.在本研究中,我们开发了针对多能性生物标记物的抗体阵列,分别以胚胎干细胞(ESCs)和鼠成纤维细胞(MEF)裂解液作为阳性和阴性对照,应用快速且无需标记的表面等离激元共振成像(SPRi)技术对i PSCs裂解液中的多种抗原进行检测.每一种抗体都与i PSC裂解液中相应的抗原显示出特异性识别.这一结果表明,SPRi技术适合于检测i PSCs裂解液中的多种抗原,并具有通用性,利用SPRi技术可以用于对干细胞裂解液中生物标志物的高通量鉴别分析.