Regeneration (Oxford, England)最新文献

{"title":"Analogous cellular contribution and healing mechanisms following digit amputation and phalangeal fracture in mice.","authors":"Lindsay A Dawson,&nbsp;Jennifer Simkin,&nbsp;Michelle Sauque,&nbsp;Maegan Pela,&nbsp;Teresa Palkowski,&nbsp;Ken Muneoka","doi":"10.1002/reg2.51","DOIUrl":"https://doi.org/10.1002/reg2.51","url":null,"abstract":"<p><p>Regeneration of amputated structures is severely limited in humans and mice, with complete regeneration restricted to the distal portion of the terminal phalanx (P3). Here, we investigate the dynamic tissue repair response of the second phalangeal element (P2) post amputation in the adult mouse, and show that the repair response of the amputated bone is similar to the proximal P2 bone fragment in fracture healing. The regeneration-incompetent P2 amputation response is characterized by periosteal endochondral ossification resulting in the deposition of new trabecular bone, corresponding to a significant increase in bone volume; however, this response is not associated with bone lengthening. We show that cells of the periosteum respond to amputation and fracture by contributing both chondrocytes and osteoblasts to the endochondral ossification response. Based on our studies, we suggest that the amputation response represents an attempt at regeneration that ultimately fails due to the lack of a distal organizing influence that is present in fracture healing.</p>","PeriodicalId":90316,"journal":{"name":"Regeneration (Oxford, England)","volume":"3 1","pages":"39-51"},"PeriodicalIF":0.0,"publicationDate":"2016-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/reg2.51","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34737332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ear wound regeneration in the African spiny mouse Acomys cahirinus.","authors":"Dino Matias Santos,&nbsp;Ana Martins Rita,&nbsp;Ignasi Casanellas,&nbsp;Adélia Brito Ova,&nbsp;Inês Maria Araújo,&nbsp;Deborah Power,&nbsp;Gustavo Tiscornia","doi":"10.1002/reg2.50","DOIUrl":"https://doi.org/10.1002/reg2.50","url":null,"abstract":"<p><p>While regeneration occurs in a number of taxonomic groups across the Metazoa, there are very few reports of regeneration in mammals, which generally respond to wounding with fibrotic scarring rather than regeneration. A recent report described skin shedding, skin regeneration and extensive ear punch closure in two rodent species, Acomys kempi and Acomys percivali. We examined these striking results by testing the capacity for regeneration of a third species, Acomys cahirinus, and found a remarkable capacity to repair full thickness circular punches in the ear pinna. Four-millimeter-diameter wounds closed completely in 2 months in 100% of ear punches tested. Histology showed extensive formation of elastic cartilage, adipose tissue, dermis, epidermis and abundant hair follicles in the repaired region. Furthermore, we demonstrated abundant angiogenesis and unequivocal presence of both muscle and nerve fibers in the reconstituted region; in contrast, similar wounds in C57BL/6 mice simply healed the borders of the cut by fibrotic scarring. Our results confirm the regenerative capabilities of Acomys, and suggest this model merits further attention.</p>","PeriodicalId":90316,"journal":{"name":"Regeneration (Oxford, England)","volume":"3 1","pages":"52-61"},"PeriodicalIF":0.0,"publicationDate":"2016-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/reg2.50","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34737333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional joint regeneration is achieved using reintegration mechanism in Xenopus laevis.","authors":"Rio Tsutsumi, Shigehito Yamada, Kiyokazu Agata","doi":"10.1002/reg2.49","DOIUrl":"10.1002/reg2.49","url":null,"abstract":"<p><p>A functional joint requires integration of multiple tissues: the apposing skeletal elements should form an interlocking structure, and muscles should insert into skeletal tissues via tendons across the joint. Whereas newts can regenerate functional joints after amputation, Xenopus laevis regenerates a cartilaginous rod without joints, a \"spike.\" Previously we reported that the reintegration mechanism between the remaining and regenerated tissues has a significant effect on regenerating joint morphogenesis during elbow joint regeneration in newt. Based on this insight into the importance of reintegration, we amputated frogs' limbs at the elbow joint and found that frogs could regenerate a functional elbow joint between the remaining tissues and regenerated spike. During regeneration, the regenerating cartilage was partially connected to the remaining articular cartilage to reform the interlocking structure of the elbow joint at the proximal end of the spike. Furthermore, the muscles of the remaining part inserted into the regenerated spike cartilage via tendons. This study might open up an avenue for analyzing molecular and cellular mechanisms of joint regeneration using Xenopus.</p>","PeriodicalId":90316,"journal":{"name":"Regeneration (Oxford, England)","volume":"3 1","pages":"26-38"},"PeriodicalIF":0.0,"publicationDate":"2016-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34737331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide analysis reveals conserved transcriptional responses downstream of resting potential change in Xenopus embryos, axolotl regeneration, and human mesenchymal cell differentiation.","authors":"Vaibhav P Pai,&nbsp;Christopher J Martyniuk,&nbsp;Karen Echeverri,&nbsp;Sarah Sundelacruz,&nbsp;David L Kaplan,&nbsp;Michael Levin","doi":"10.1002/reg2.48","DOIUrl":"https://doi.org/10.1002/reg2.48","url":null,"abstract":"<p><p>Endogenous bioelectric signaling via changes in cellular resting potential (V mem) is a key regulator of patterning during regeneration and embryogenesis in numerous model systems. Depolarization of V mem has been functionally implicated in dedifferentiation, tumorigenesis, anatomical re-specification, and appendage regeneration. However, no unbiased analyses have been performed to understand genome-wide transcriptional responses to V mem change in vivo. Moreover, it is unknown which genes or gene networks represent conserved targets of bioelectrical signaling across different patterning contexts and species. Here, we use microarray analysis to comparatively analyze transcriptional responses to V mem depolarization. We compare the response of the transcriptome during embryogenesis (Xenopus development), regeneration (axolotl regeneration), and stem cell differentiation (human mesenchymal stem cells in culture) to identify common networks across model species that are associated with depolarization. Both subnetwork enrichment and PANTHER analyses identified a number of key genetic modules as targets of V mem change, and also revealed important (well-conserved) commonalities in bioelectric signal transduction, despite highly diverse experimental contexts and species. Depolarization regulates specific transcriptional networks across all three germ layers (ectoderm, mesoderm, and endoderm) such as cell differentiation and apoptosis, and this information will be used for developing mechanistic models of bioelectric regulation of patterning. Moreover, our analysis reveals that V mem change regulates transcripts related to important disease pathways such as cancer and neurodegeneration, which may represent novel targets for emerging electroceutical therapies. </p>","PeriodicalId":90316,"journal":{"name":"Regeneration (Oxford, England)","volume":"3 1","pages":"3-25"},"PeriodicalIF":0.0,"publicationDate":"2015-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/reg2.48","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34737330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regeneration and repair of human digits and limbs: fact and fiction.","authors":"Shyh-Jou Shieh,&nbsp;Tsun-Chih Cheng","doi":"10.1002/reg2.41","DOIUrl":"https://doi.org/10.1002/reg2.41","url":null,"abstract":"<p><p>A variety of digit and limb repair and reconstruction methods have been used in different clinical settings, but regeneration remains an item on every plastic surgeon's \"wish list.\" Although surgical salvage techniques are continually being improved, unreplantable digits and limbs are still abundant. We comprehensively review the structural and functional salvage methods in clinical practice, from the peeling injuries of small distal fingertips to multisegmented amputated limbs, and the developmental and tissue engineering approaches for regenerating human digits and limbs in the laboratory. Although surgical techniques have forged ahead, there are still situations in which digits and limbs are unreplantable. Advances in the field are delineated, and the regeneration processes of salamander limbs, lizard tails, and mouse digits and each component of tissue engineering approaches for digit- and limb-building are discussed. Although the current technology is promising, there are many challenges in human digit and limb regeneration. We hope this review inspires research on the critical gap between clinical and basic science, and leads to more sophisticated digit and limb loss rescue and regeneration innovations.</p>","PeriodicalId":90316,"journal":{"name":"Regeneration (Oxford, England)","volume":"2 4","pages":"149-68"},"PeriodicalIF":0.0,"publicationDate":"2015-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/reg2.41","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34349782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positional information in axolotl and mouse limb extracellular matrix is mediated via heparan sulfate and fibroblast growth factor during limb regeneration in the axolotl (Ambystoma mexicanum).","authors":"Anne Q Phan,&nbsp;Jangwoo Lee,&nbsp;Michelle Oei,&nbsp;Craig Flath,&nbsp;Caitlyn Hwe,&nbsp;Rachele Mariano,&nbsp;Tiffany Vu,&nbsp;Cynthia Shu,&nbsp;Andrew Dinh,&nbsp;Jennifer Simkin,&nbsp;Ken Muneoka,&nbsp;Susan V Bryant,&nbsp;David M Gardiner","doi":"10.1002/reg2.40","DOIUrl":"https://doi.org/10.1002/reg2.40","url":null,"abstract":"<p><p>Urodele amphibians are unique among adult vertebrates in their ability to regenerate complex body structures after traumatic injury. In salamander regeneration, the cells maintain a memory of their original position and use this positional information to recreate the missing pattern. We used an in vivo gain-of-function assay to determine whether components of the extracellular matrix (ECM) have positional information required to induce formation of new limb pattern during regeneration. We discovered that salamander limb ECM has a position-specific ability to either inhibit regeneration or induce de novo limb structure, and that this difference is dependent on heparan sulfates that are associated with differential expression of heparan sulfate sulfotransferases. We also discovered that an artificial ECM containing only heparan sulfate was sufficient to induce de novo limb pattern in salamander limb regeneration. Finally, ECM from mouse limbs is capable of inducing limb pattern in axolotl blastemas in a position-specific, developmental-stage-specific, and heparan sulfate-dependent manner. This study demonstrates a mechanism for positional information in regeneration and establishes a crucial functional link between salamander regeneration and mammals. </p>","PeriodicalId":90316,"journal":{"name":"Regeneration (Oxford, England)","volume":"2 4","pages":"182-201"},"PeriodicalIF":0.0,"publicationDate":"2015-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/reg2.40","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34349783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal callus formation is a nerve-independent regenerative response to limb amputation in mice and Xenopus.","authors":"Shinichirou Miura,&nbsp;Yumiko Takahashi,&nbsp;Akira Satoh,&nbsp;Tetsuya Endo","doi":"10.1002/reg2.39","DOIUrl":"https://doi.org/10.1002/reg2.39","url":null,"abstract":"<p><p>To clarify the mechanism of limb regeneration that differs between mammals (non-regenerative) and amphibians (regenerative), responses to limb amputation and the accessory limb inducible surgery (accessory limb model, ALM) were compared between mice and Xenopus, focusing on the events leading to blastema formation. In both animals, cartilaginous calluses were formed around the cut edge of bones after limb amputation. They not only are morphologically similar but show other similarities, such as growth driven by undifferentiated cell proliferation and macrophage-dependent and nerve-independent induction. It appears that amputation callus formation is a common nerve-independent regenerative response in mice and Xenopus. In contrast, the ALM revealed that the wound epithelium (WE) in Xenopus was innervated by many regenerating axons when a severed nerve ending was placed underneath it, whereas only a few axons were found within the WE in mice. Since nerves are involved in induction of the regeneration-permissive WE in amphibians, whether or not nerves can interact with the WE might be one of the key processes separating successful nerve-dependent blastema formation in Xenopus and failure in mice. </p>","PeriodicalId":90316,"journal":{"name":"Regeneration (Oxford, England)","volume":"2 4","pages":"202-16"},"PeriodicalIF":0.0,"publicationDate":"2015-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/reg2.39","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34737329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Principles and mechanisms of regeneration in the mouse model for wound-induced hair follicle neogenesis.","authors":"Xiaojie Wang,&nbsp;Tsai-Ching Hsi,&nbsp;Christian Fernando Guerrero-Juarez,&nbsp;Kim Pham,&nbsp;Kevin Cho,&nbsp;Catherine D McCusker,&nbsp;Edwin S Monuki,&nbsp;Ken W Y Cho,&nbsp;Denise L Gay,&nbsp;Maksim V Plikus","doi":"10.1002/reg2.38","DOIUrl":"https://doi.org/10.1002/reg2.38","url":null,"abstract":"<p><p>Wound induced hair follicle neogenesis (WIHN) describes a regenerative phenomenon in adult mammalian skin, wherein fully functional hair follicles regenerate <i>de novo</i> in the center of large excisional wounds. Originally described in rats, rabbits, sheep, and humans in 1940-60, the WIHN phenomenon was reinvestigated in mice only recently. The process of <i>de novo</i> hair regeneration largely duplicates the morphological and signaling features of normal embryonic hair development. Similar to hair development, WIHN critically depends on the activation of canonical WNT signaling. However, unlike hair development, WNT activation in WIHN is dependent on Fgf9 signaling generated by the immune system's gamma delta (γδ) T cells. The cellular bases of WIHN remain to be fully characterized, however, the available evidence leaves open the possibility for a blastema-like mechanism, wherein epidermal and/or dermal wound cells undergo epigenetic reprogramming toward a more plastic, embryonic-like state. <i>De novo</i> hair follicles do not regenerate from preexisting hair-fated bulge stem cells. This suggests that hair neogenesis is not driven by preexisting lineage-restricted progenitors, as is the case for amputation-induced mouse digit tip regeneration, but rather may require a blastema-like mechanism. The WIHN model is characterized by several intriguing features, which await further explanation. These include: (i) minimum wound size requirement for activating neogenesis, (ii) restriction of hair neogenesis to the wound's center, (iii) imperfect patterning outcomes, both in terms of neogenic hair positioning within the wound and in terms of their orientation. Future inquires into the WIHN process, made possible by a wide array of the available skin-specific genetic tools, will undoubtedly expand our understanding of the regeneration mechanisms in adult mammals.</p>","PeriodicalId":90316,"journal":{"name":"Regeneration (Oxford, England)","volume":"2 4","pages":"169-181"},"PeriodicalIF":0.0,"publicationDate":"2015-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/reg2.38","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34187769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mammalian blastema: regeneration at our fingertips.","authors":"Jennifer Simkin,&nbsp;Mimi C Sammarco,&nbsp;Lindsay A Dawson,&nbsp;Paula P Schanes,&nbsp;Ling Yu,&nbsp;Ken Muneoka","doi":"10.1002/reg2.36","DOIUrl":"https://doi.org/10.1002/reg2.36","url":null,"abstract":"<p><p>In the mouse, digit tip regeneration progresses through a series of discrete stages that include inflammation, histolysis, epidermal closure, blastema formation, and redifferentiation. Recent studies reveal how each regenerative stage influences subsequent stages to establish a blastema that directs the successful regeneration of a complex mammalian structure. The focus of this review is on early events of healing and how an amputation wound transitions into a functional blastema. The stepwise formation of a mammalian blastema is proposed to provide a model for how specific targeted treatments can enhance regenerative performance in humans. </p>","PeriodicalId":90316,"journal":{"name":"Regeneration (Oxford, England)","volume":"2 3","pages":"93-105"},"PeriodicalIF":0.0,"publicationDate":"2015-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/reg2.36","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34349780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidermal closure regulates histolysis during mammalian (Mus) digit regeneration.","authors":"Jennifer Simkin,&nbsp;Mimi C Sammarco,&nbsp;Lindsay A Dawson,&nbsp;Catherine Tucker,&nbsp;Louis J Taylor,&nbsp;Keith Van Meter,&nbsp;Ken Muneoka","doi":"10.1002/reg2.34","DOIUrl":"https://doi.org/10.1002/reg2.34","url":null,"abstract":"<p><p>Mammalian digit regeneration progresses through consistent stages: histolysis, inflammation, epidermal closure, blastema formation, and finally redifferentiation. What we do not yet know is how each stage can affect others. Questions of stage timing, tissue interactions, and microenvironmental states are becoming increasingly important as we look toward solutions for whole limb regeneration. This study focuses on the timing of epidermal closure which, in mammals, is delayed compared to more regenerative animals like the axolotl. We use a standard wound closure device, Dermabond (2-octyl cyanoacrylate), to induce earlier epidermal closure, and we evaluate the effect of fast epidermal closure on histolysis, blastema formation, and redifferentiation. We find that fast epidermal closure is reliant upon a hypoxic microenvironment. Additionally, early epidermal closure eliminates the histolysis stage and results in a regenerate that more closely replicates the amputated structure. We show that tools like Dermabond and oxygen are able to independently influence the various stages of regeneration enabling us to uncouple histolysis, wound closure, and other regenerative events. With this study, we start to understand how each stage of mammalian digit regeneration is controlled.</p>","PeriodicalId":90316,"journal":{"name":"Regeneration (Oxford, England)","volume":"2 3","pages":"106-19"},"PeriodicalIF":0.0,"publicationDate":"2015-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/reg2.34","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34349781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}