Regenerative medicine

  • Article
    | Open Access

    Mesenchymal stromal cells enhance bone and cartilage repair, but are limited by poor survival and retention after transplantation. Here, the authors show that synthetic hydrogels presenting integrin-specific peptides enhance the survival and persistence of human mesenchymal stromal cells after transplant, as well as bone repair.

    • Amy Y. Clark
    • , Karen E. Martin
    • , José R. García
    • , Christopher T. Johnson
    • , Hannah S. Theriault
    • , Woojin M. Han
    • , Dennis W. Zhou
    • , Edward A. Botchwey
    •  & Andrés J. García
  • Article
    | Open Access

    Extracellular matrix (ECM) is an ideal scaffold for tissue engineering but tends to lack hierarchical structure. Here the authors implant sacrificial templates subcutaneously to build an organised ECM scaffold, and following template removal and decellularisation use these scaffolds to create functionally integrated muscle, nerve and artery in vivo.

    • Meifeng Zhu
    • , Wen Li
    • , Xianhao Dong
    • , Xingyu Yuan
    • , Adam C. Midgley
    • , Hong Chang
    • , Yuhao Wang
    • , Haoyu Wang
    • , Kai Wang
    • , Peter X. Ma
    • , Hongjun Wang
    •  & Deling Kong
  • Article
    | Open Access

    Islet transplantation is a feasible approach to treat type I diabetes, however inflammation and poor vascularisation impair long-term engraftment. Here the authors show that incorporating human amniotic epithelial cells into islet organoids improves engraftment and function of organoids, through enhanced revascularisation.

    • Fanny Lebreton
    • , Vanessa Lavallard
    • , Kevin Bellofatto
    • , Romain Bonnet
    • , Charles H. Wassmer
    • , Lisa Perez
    • , Vakhtang Kalandadze
    • , Antonia Follenzi
    • , Michel Boulvain
    • , Julie Kerr-Conte
    • , David J. Goodman
    • , Domenico Bosco
    • , Thierry Berney
    •  & Ekaterine Berishvili
  • Article
    | Open Access

    The liver parenchyma consists of several cell types, but the origin of this tissue in humans is unclear. Here, the authors perform single cell RNA sequencing of human fetal and adult liver to identify a hepatobiliary hybrid progenitor population of cells, which have a similar gene signature to mouse oval cells.

    • Joe M. Segal
    • , Deniz Kent
    • , Daniel J. Wesche
    • , Soon Seng Ng
    • , Maria Serra
    • , Bénédicte Oulès
    • , Gozde Kar
    • , Guy Emerton
    • , Samuel J. I. Blackford
    • , Spyros Darmanis
    • , Rosa Miquel
    • , Tu Vinh Luong
    • , Ryo Yamamoto
    • , Andrew Bonham
    • , Wayel Jassem
    • , Nigel Heaton
    • , Alessandra Vigilante
    • , Aileen King
    • , Rocio Sancho
    • , Sarah Teichmann
    • , Stephen R. Quake
    • , Hiromitsu Nakauchi
    •  & S. Tamir Rashid
  • Article
    | Open Access

    The incorporation of cells into tissue engineering scaffolds can be a major challenge. Here, the authors report on anchoring thrombin to cell membranes for the in situ formation of fibrin scaffolds around the modified cells, demonstrate scaffold formation in vitro and show cell survival in vivo.

    • Robert C. Deller
    • , Thomas Richardson
    • , Rebecca Richardson
    • , Laura Bevan
    • , Ioannis Zampetakis
    • , Fabrizio Scarpa
    •  & Adam W. Perriman
  • Article
    | Open Access

    The use of pluripotent-stem cell derived organs for transplantation would be promising, if organs can be grown in a suitable host. Here, the authors use interspecific blastocyst complementation to generate a mouse pluripotent stem cell-derived kidney in anephric Sall1 mutant rats.

    • Teppei Goto
    • , Hiromasa Hara
    • , Makoto Sanbo
    • , Hideki Masaki
    • , Hideyuki Sato
    • , Tomoyuki Yamaguchi
    • , Shinichi Hochi
    • , Toshihiro Kobayashi
    • , Hiromitsu Nakauchi
    •  & Masumi Hirabayashi
  • Article
    | Open Access

    Heart grafts need good vascularization to survive. Here, the authors engineer perfusable constructs of human embryonic stem cell-derived endothelial cells seeded in collagen matrix in patterned microchannels that form anastomosed vessels in vitro and have increased coronary vascular perfusion on transplantation in rats.

    • Meredith A. Redd
    • , Nicole Zeinstra
    • , Wan Qin
    • , Wei Wei
    • , Amy Martinson
    • , Yuliang Wang
    • , Ruikang K. Wang
    • , Charles E. Murry
    •  & Ying Zheng
  • Article
    | Open Access

    Lineage segregation from conception to gastrulation has been mapped at the single cell level in mouse, human and monkey. Here, the authors provide a comprehensive analysis of porcine preimplantation development using single cell RNA-seq; mapping metabolic changes, X chromosome inactivation and signalling pathways.

    • Priscila Ramos-Ibeas
    • , Fei Sang
    • , Qifan Zhu
    • , Walfred W. C. Tang
    • , Sarah Withey
    • , Doris Klisch
    • , Liam Wood
    • , Matt Loose
    • , M. Azim Surani
    •  & Ramiro Alberio
  • Article
    | Open Access

    Engineering 3D tissues faces the challenge of adequate vascularisation for nutrient delivery and gas exchange deep inside the construct. Here the authors use surface acoustic waves to create an aligned array of blood vessels in a hyaluronic acid hydrogel and use it to improve function in a mouse hindlimb ischemia model.

    • Byungjun Kang
    • , Jisoo Shin
    • , Hyun-Ji Park
    • , Chanryeol Rhyou
    • , Donyoung Kang
    • , Shin-Jeong Lee
    • , Young-sup Yoon
    • , Seung-Woo Cho
    •  & Hyungsuk Lee
  • Article
    | Open Access

    Combining decellularised scaffolds with patient-derived cells holds promise for bioengineering of functional tissues. Here the authors develop a two-stage approach to engineer an oesophageal graft that retains the structural organisation of native oesophagus.

    • Luca Urbani
    • , Carlotta Camilli
    • , Demetra-Ellie Phylactopoulos
    • , Claire Crowley
    • , Dipa Natarajan
    • , Federico Scottoni
    • , Panayiotis Maghsoudlou
    • , Conor J. McCann
    • , Alessandro Filippo Pellegata
    • , Anna Urciuolo
    • , Koichi Deguchi
    • , Sahira Khalaf
    • , Salvatore Ferdinando Aruta
    • , Maria Cristina Signorelli
    • , David Kiely
    • , Edward Hannon
    • , Matteo Trevisan
    • , Rui Rachel Wong
    • , Marc Olivier Baradez
    • , Dale Moulding
    • , Alex Virasami
    • , Asllan Gjinovci
    • , Stavros Loukogeorgakis
    • , Sara Mantero
    • , Nikhil Thapar
    • , Neil Sebire
    • , Simon Eaton
    • , Mark Lowdell
    • , Giulio Cossu
    • , Paola Bonfanti
    •  & Paolo De Coppi
  • Article
    | Open Access

    In vivo reprogramming of somatic cells is hampered by the need for vectors to express the OKSM factors in selected organs. Here the authors report new AAV-based vectors capable of in vivo reprogramming at low doses.

    • Elena Senís
    • , Lluc Mosteiro
    • , Stefan Wilkening
    • , Ellen Wiedtke
    • , Ali Nowrouzi
    • , Saira Afzal
    • , Raffaele Fronza
    • , Henrik Landerer
    • , Maria Abad
    • , Dominik Niopek
    • , Manfred Schmidt
    • , Manuel Serrano
    •  & Dirk Grimm
  • Article
    | Open Access

    Laminins are important regulators of epidermal wound healing. Here, the authors show that laminins bind to multiple growth factors via their heparin-binding domains, and that incorporation of these domains into fibrin matrices increases growth factor retention, promoting wound healing in type 2 diabetic mouse models.

    • Jun Ishihara
    • , Ako Ishihara
    • , Kazuto Fukunaga
    • , Koichi Sasaki
    • , Michael J. V. White
    • , Priscilla S. Briquez
    •  & Jeffrey A. Hubbell
  • Article
    | Open Access

    Personalised medicine requires cell cultures from defined genetic backgrounds, but providing sufficient numbers of cells is a challenge. Here the authors develop gene cocktails to expand primary cells from a variety of different tissues and species, and show that expanded endothelial and hepatic cells retain properties of the differentiated phenotype.

    • Christoph Lipps
    • , Franziska Klein
    • , Tom Wahlicht
    • , Virginia Seiffert
    • , Milada Butueva
    • , Jeannette Zauers
    • , Theresa Truschel
    • , Martin Luckner
    • , Mario Köster
    • , Roderick MacLeod
    • , Jörn Pezoldt
    • , Jochen Hühn
    • , Qinggong Yuan
    • , Peter Paul Müller
    • , Henning Kempf
    • , Robert Zweigerdt
    • , Oliver Dittrich-Breiholz
    • , Thomas Pufe
    • , Rainer Beckmann
    • , Wolf Drescher
    • , Jose Riancho
    • , Carolina Sañudo
    • , Thomas Korff
    • , Bertram Opalka
    • , Vera Rebmann
    • , Joachim R. Göthert
    • , Paula M. Alves
    • , Michael Ott
    • , Roland Schucht
    • , Hansjörg Hauser
    • , Dagmar Wirth
    •  & Tobias May
  • Article
    | Open Access

    There is a need for humanised grafts to treat patients with intestinal failure. Here, the authors generate intestinal grafts by recellularizing native intestinal matrix with human induced pluripotent stem cell-derived epithelium and human endothelium, and show nutrient absorption after transplantation in rats.

    • Kentaro Kitano
    • , Dana M. Schwartz
    • , Haiyang Zhou
    • , Sarah E. Gilpin
    • , Gregory R. Wojtkiewicz
    • , Xi Ren
    • , Cesar A. Sommer
    • , Amalia V. Capilla
    • , Douglas J. Mathisen
    • , Allan M. Goldstein
    • , Gustavo Mostoslavsky
    •  & Harald C. Ott
  • Article
    | Open Access

    Soluble vascular endothelial growth factor (VEGF) enhances vascular engraftment of transplanted cells but the efficacy is low. Here, the authors show that VEGF-immobilized microparticles prolong survival of endothelial progenitors in vitro and in vivo by downregulating miR17 and upregulating CDKN1A and ZNF652.

    • Sezin Aday
    • , Janet Zoldan
    • , Marie Besnier
    • , Laura Carreto
    • , Jaimy Saif
    • , Rui Fernandes
    • , Tiago Santos
    • , Liliana Bernardino
    • , Robert Langer
    • , Costanza Emanueli
    •  & Lino Ferreira
  • Article
    | Open Access

    Integration of transplanted photoreceptors into the host retina has been assumed as the underlying mechanism for vision improvement in pre-clinical studies. Here, the authors show that the majority of transplanted photoreceptors do not structurally integrate but exchange intercellular material with host cells.

    • Tiago Santos-Ferreira
    • , Sílvia Llonch
    • , Oliver Borsch
    • , Kai Postel
    • , Jochen Haas
    •  & Marius Ader
  • Article
    | Open Access

    Transplantation of healthy photoreceptor cells has been shown to rescue blindness. Here, the authors show that rather than donor cells integrating into the host retina, the predominant mechanism underlying this rescue involves exchange of cytoplasmic material between donor and host cells in vivo.

    • R. A. Pearson
    • , A. Gonzalez-Cordero
    • , E. L. West
    • , J. R. Ribeiro
    • , N. Aghaizu
    • , D. Goh
    • , R. D. Sampson
    • , A. Georgiadis
    • , P. V. Waldron
    • , Y. Duran
    • , A. Naeem
    • , M. Kloc
    • , E. Cristante
    • , K. Kruczek
    • , K. Warre-Cornish
    • , J. C. Sowden
    • , A. J. Smith
    •  & R. R. Ali
  • Article
    | Open Access

    Current vessel grafts must be surgically replaced when the recipient outgrows them. Here, Syedain et al.bioengineer a tube of acellular matrix produced from sheep fibroblasts that is capable of cellularizaton and somatic growth when transplanted into growing lambs, eliminating the need for multiple graft surgeries.

    • Zeeshan Syedain
    • , Jay Reimer
    • , Matthew Lahti
    • , James Berry
    • , Sandra Johnson
    • , Richard Bianco
    •  & Robert T. Tranquillo
  • Article
    | Open Access

    Synthetic biology offers the potential for the design and implementation of rationally designed, complex genetic programmes. Here the authors design a genetic network to trigger the differentiation of patient derived IPSCs into beta-like cells.

    • Pratik Saxena
    • , Boon Chin Heng
    • , Peng Bai
    • , Marc Folcher
    • , Henryk Zulewski
    •  & Martin Fussenegger
  • Article
    | Open Access

    Cell therapy requires sufficient amounts of therapeutic cells to be delivered to the injured tissue. Here the authors use magnetic iron nanoparticles conjugated with antibodies that bind therapeutic cells and cardiomyocytes to treat myocardial ischemia/reperfusion injury in rats and show that targeting to the heart is enhanced upon local application of a magnetic field.

    • Ke Cheng
    • , Deliang Shen
    • , M. Taylor Hensley
    • , Ryan Middleton
    • , Baiming Sun
    • , Weixin Liu
    • , Geoffrey De Couto
    •  & Eduardo Marbán
  • Article |

    Induced pluripotent stem cells (iPSCs) hold great potential for modelling human developmental processes and diseases. Here the authors induce human iPSCs to spontaneously form fully laminated three-dimensional retinal tissue containing functional photoreceptor cells.

    • Xiufeng Zhong
    • , Christian Gutierrez
    • , Tian Xue
    • , Christopher Hampton
    • , M. Natalia Vergara
    • , Li-Hui Cao
    • , Ann Peters
    • , Tea Soon Park
    • , Elias T. Zambidis
    • , Jason S. Meyer
    • , David M. Gamm
    • , King-Wai Yau
    •  & M. Valeria Canto-Soler
  • Article
    | Open Access

    Lacrimal glands maintain a healthy corneal epithelium but are dysfunctional for example in dry-eye disease. Here, the authors transplant bioengineered lacrimal and harderian gland germs into mice, where they connect to the host duct and nervous system and restore lacrimal gland function.

    • Masatoshi Hirayama
    • , Miho Ogawa
    • , Masamitsu Oshima
    • , Yurie Sekine
    • , Kentaro Ishida
    • , Kentaro Yamashita
    • , Kazutaka Ikeda
    • , Shigeto Shimmura
    • , Tetsuya Kawakita
    • , Kazuo Tsubota
    •  & Takashi Tsuji
  • Article
    | Open Access

    Salivary gland dysfunction as a result of diseases or ageing reduces the quality of life and causes various oral health problems. Here the authors show that the salivary gland function of mice can be recovered by orthotopic transplantation of a bioengineered salivary gland germ.

    • Miho Ogawa
    • , Masamitsu Oshima
    • , Aya Imamura
    • , Yurie Sekine
    • , Kentaro Ishida
    • , Kentaro Yamashita
    • , Kei Nakajima
    • , Masatoshi Hirayama
    • , Tetsuhiko Tachikawa
    •  & Takashi Tsuji
  • Article |

    Artificial heart tissue may find application in novel therapies of cardiac disease in the future. Here, Lu et al. take a step towards the creation of personalized heart tissue by repopulating decellularized mouse hearts with cells derived from human induced pluripotent stem cells.

    • Tung-Ying Lu
    • , Bo Lin
    • , Jong Kim
    • , Mara Sullivan
    • , Kimimasa Tobita
    • , Guy Salama
    •  & Lei Yang
  • Article |

    The potential tumorigenicity of human pluripotent stem cells (hPSCs) limits their application in cell therapies. Ben-David et al.identify the tight-junction protein Claudin-6 as a cell-surface marker of hPSCs, and demonstrate three Claudin-6-based strategies to remove tumorigenic hPSCs from mixed cell cultures.

    • Uri Ben-David
    • , Neta Nudel
    •  & Nissim Benvenisty
  • Article |

    Stem cells have raised hopes of developing regenerative therapies of renal disease. Here, Osafune et al.provide a protocol for the differentiation of induced human pluripotent stem cells into renal lineages with the capacity to form tubular renal structures in mice.

    • Shin-Ichi Mae
    • , Akemi Shono
    • , Fumihiko Shiota
    • , Tetsuhiko Yasuno
    • , Masatoshi Kajiwara
    • , Nanaka Gotoda-Nishimura
    • , Sayaka Arai
    • , Aiko Sato-Otubo
    • , Taro Toyoda
    • , Kazutoshi Takahashi
    • , Naoki Nakayama
    • , Chad A. Cowan
    • , Takashi Aoi
    • , Seishi Ogawa
    • , Andrew P. McMahon
    • , Shinya Yamanaka
    •  & Kenji Osafune
  • Article
    | Open Access

    Signalling inputs to neural progenitors regulate the differentiation of the stem cell pool. By analysing the mechanisms occuring during neurogenesis, Cambrayet al. report that activin is the pivotal factor regulating the differentiation of telencephalic neural precursors towards a cortical interneuron fate.

    • Serafí Cambray
    • , Charles Arber
    • , Graham Little
    • , Antonios G. Dougalis
    • , Vincenzo de Paola
    • , Mark A. Ungless
    • , Meng Li
    •  & Tristan A. Rodríguez
  • Article
    | Open Access

    Bioengineered hair follicles can be produced from embryonic follicle germ cells, but whether these follicles can interact with the surrounding tissue and function normally is unknown. Here, bioengineered hair follicles transplanted into mouse dermis make connections with the surrounding tissue and show normal hair cycles.

    • Koh-ei Toyoshima
    • , Kyosuke Asakawa
    • , Naoko Ishibashi
    • , Hiroshi Toki
    • , Miho Ogawa
    • , Tomoko Hasegawa
    • , Tarou Irié
    • , Tetsuhiko Tachikawa
    • , Akio Sato
    • , Akira Takeda
    •  & Takashi Tsuji