Featured
-
-
Article
| Open Access
Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function
A systemically administered peptide (CARSKNKDC) that homes to injured tissues, has inherent ability to promote wound healing. Here, the authors show that this peptide binds to syndecan-4 and activates ARF6 to trigger re-epithelialisation and the naturally occurring wound repair pathway.
- Horacio Maldonado
- , Bryan D. Savage
- & Tero A. H. Järvinen
-
Article
| Open Access
Occlusive membranes for guided regeneration of inflamed tissue defects
Symbiosis should be maintained during the oral regeneration period. Herein, authors develop an occlusive membrane that induces symbiosis, thereby improving the performance of guided bone generation therapy.
- Woojin Choi
- , Utkarsh Mangal
- & Jinkee Hong
-
Article
| Open Access
Enhanced pericyte-endothelial interactions through NO-boosted extracellular vesicles drive revascularization in a mouse model of ischemic injury
Treatment alternatives are not available for a significant portion of critical limb ischemia patients. Here, the authors show a strategy to engineer mesenchymal stem cells-derived extracellular vesicles to induce revascularization in mice.
- Ling Guo
- , Qiang Yang
- & Min Feng
-
Article
| Open Access
Emergence of task-related spatiotemporal population dynamics in transplanted neurons
Cell therapy is a promising treatment for brain injury, but it is unclear if transplanted neurons demonstrate population dynamics. By monitoring transplanted neurons in injured mice, here the authors show the emergence of dynamics resembling intact networks.
- Harman Ghuman
- , Kyungsoo Kim
- & Karunesh Ganguly
-
Article
| Open Access
Unaltered hepatic wound healing response in male rats with ancestral liver injury
How much the environment influences inherited adaptive traits is debated and challenging to demonstrate in mammals. Here the authors performed a multigeneration study that failed to morphologically replicate enhanced wound healing response following ancestral liver injury in rats. However, heritable transcriptional effects suggest transmission at the molecular level, albeit of unclear functional relevance.
- Johanna Beil
- , Juliane Perner
- & Rémi Terranova
-
Article
| Open Access
Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice
Brain injuries can result in significant damage to the cerebral cortex, and restoring the cellular architecture of the tissue remains challenging. Here, the authors use a droplet printing technique to fabricate a simplified human cerebral cortical column and demonstrate its functionality and potential for future personalized therapy approaches.
- Yongcheng Jin
- , Ellina Mikhailova
- & Hagan Bayley
-
Article
| Open Access
Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing
Chronic wounds impose a significant burden to a broad patient population. Here, the authors use CRISPR/Cas9 to enhance the regenerative capacity of dendritic cells by knocking out the gene Ndrg2, and show that seeding these engineered dendritic cells on hydrogels constitutes an effective therapy for chronic wounds in diabetic and non-diabetic conditions.
- Dominic Henn
- , Dehua Zhao
- & Geoffrey C. Gurtner
-
Article
| Open Access
Transplanting FVIII/ET3-secreting cells in fetal sheep increases FVIII levels long-term without inducing immunity or toxicity
The authors show in a preclinical large animal model that in utero delivery of FVIII-secreting human placental cells is feasible, safe, and yields elevated plasma FVIII activity for at least three years without triggering immunity, affirming prenatal treatment of hemophilia A.
- Martin Rodriguez
- , Brady Trevisan
- & Graça Almeida-Porada
-
Article
| Open Access
In situ activation of flexible magnetoelectric membrane enhances bone defect repair
Biomaterials that can be non-invasively activated to promote bone growth would be useful tools to repair bone defects in patients with comorbidities like inflammation or impaired osteogenesis. Here, the authors develop a composite membrane that can be stimulated by an external magnetic field and use it to correct skull defects in rats treated to reflect such comorbidities.
- Wenwen Liu
- , Han Zhao
- & Xuliang Deng
-
Article
| Open Access
Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect
Allogeneic iPSC-derived cartilage organoids survive and integrate with surrounding native cartilage without immune reactions in a primate model of chondral defects in the knee joints, being remodeled and functioning as articular cartilage.
- Kengo Abe
- , Akihiro Yamashita
- & Noriyuki Tsumaki
-
Article
| Open Access
Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation
Bioengineered livers using decellularized scaffolds have been considered as an alternative to donor organs. Here, the authors modulate biophysical properties of decellularized scaffolds by crosslinking with nano-graphene oxide, thereby greatly enhancing therapeutic efficacy of bioengineered livers.
- Da-Hyun Kim
- , Min-Ji Kim
- & Kyung-Sun Kang
-
Article
| Open Access
Bead-jet printing enabled sparse mesenchymal stem cell patterning augments skeletal muscle and hair follicle regeneration
Current mesenchymal stem cell (MSC) transplantation practices are limited by the loss or reduced performance of MSCs. Here the authors develop a bead-jet printer for intraoperative formulation and printing of MSCs-laden Matrigel beads to improve skeletal muscle and hair follicle regeneration.
- Yuanxiong Cao
- , Jiayi Tan
- & Shaohua Ma
-
Article
| Open Access
Rapid joule heating improves vitrification based cryopreservation
Lower concentrations of toxic cryoprotective agents require rapid and scalable rewarming techniques. Here, the authors report on a joule heating–based platform where samples are rapidly rewarmed by contact with a voltage pulsed electrical conductor and demonstrate the preservation of Drosophila embryos and rat kidney slices.
- Li Zhan
- , Zonghu Han
- & John C. Bischof
-
Article
| Open Access
In situ 3D bioprinting with bioconcrete bioink
Bioinks used in current in-situ bioprinting have limitations when applied to complex operational environments. Here, the authors report on the creation of a microgel reinforced GelMA bioink which can be simply prepared and used in different biomedical settings. The application is demonstrated in a cranial defect model.
- Mingjun Xie
- , Yang Shi
- & Yong He
-
Article
| Open Access
An instantly fixable and self-adaptive scaffold for skull regeneration by autologous stem cell recruitment and angiogenesis
Limited stem cells and mismatched interface fusion have plagued biomaterial-mediated cranial reconstruction. Here, the authors engineer an instantly fixable and self-adaptive scaffold to promote calcium chelation and interface integration, regulate macrophage M2 polarization, and recruit endogenous stem cells.
- Gonggong Lu
- , Yang Xu
- & Xingdong Zhang
-
Article
| Open Access
CRISPR-enhanced human adipocyte browning as cell therapy for metabolic disease
Worldwide pandemics of obesity and diabetes prompt an urgent need for new approaches to their prevention and cure. Here the authors present a CRISPR-based strategy that enhances the therapeutic potential of human adipocytes when implanted in obese mice.
- Emmanouela Tsagkaraki
- , Sarah M. Nicoloro
- & Michael P. Czech
-
Article
| Open Access
Nuclear S-nitrosylation impacts tissue regeneration in zebrafish
The role of the post-translational modifications in tissue regeneration is still not clearly understood. Here, the authors show that many nuclear proteins change S-nitrosylation state in the regenerating zebrafish tailfin, highlighting the importance of Kdm1a S-nitrosylation in the repair process.
- Gianfranco Matrone
- , Sung Yun Jung
- & John P. Cooke
-
Article
| Open Access
Disrupting biological sensors of force promotes tissue regeneration in large organisms
Humans and other large mammals heal wounds by forming fibrotic scar tissue with diminished function. Here, the authors show that disrupting mechanotransduction through the focal adhesion kinase pathway in large animals accelerates healing, prevents fibrosis, and enhances skin regeneration.
- Kellen Chen
- , Sun Hyung Kwon
- & Geoffrey C. Gurtner
-
Article
| Open Access
Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture
Tendon self-renewal occurs rarely and reconstructive surgery comes with significant limitations. Here the authors present an induced pluripotent stem cell-based method to generate tenocytes, analyze their developmental trajectory using scRNA-seq, and demonstrate their contribution to motor function recovery after Achilles tendon injury via engraftment and paracrine effects.
- Taiki Nakajima
- , Akihiro Nakahata
- & Makoto Ikeya
-
Article
| Open Access
Development of selective bispecific Wnt mimetics for bone loss and repair
Antibody-based Wnt agonists are able to phenocopy Wnt signaling in vivo resulting in increased bone density, repair, and strength. Here, the authors show that Wnt agonists can reverse bone loss associated with ovariectomy and build stronger bone when administered after fracture.
- Tristan W. Fowler
- , Troy L. Mitchell
- & Yang Li
-
Article
| Open Access
A human antibody selective for transthyretin amyloid removes cardiac amyloid through phagocytic immune cells
Analyzing memory B cell repertoires of the healthy elderly enabled Michalon et al. to develop a recombinant human antibody selective for transthyretin amyloid. This antibody removes cardiac amyloid through recruitment of phagocytic immune cells.
- Aubin Michalon
- , Andreas Hagenbuch
- & Jan Grimm
-
Article
| Open Access
A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy
T-cell immunotherapies, such as CAR-T immunotherapy, are being developed against a wide variety of diseases. Here the authors report the feeder-free, scalable differentiation of human induced pluripotent cells (iPSCs) to T-cells with T-cell receptor dependent anti-tumour function in vitro and in vivo.
- Shoichi Iriguchi
- , Yutaka Yasui
- & Shin Kaneko
-
Article
| Open Access
Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds
The thymus is essential for T cell maturation and selection, and thymic defects result in severe immune problems. Here the authors identify a thymus cell population that is expandable in vitro, and can repopulate natural thymic matrix to generate tissue that supports mature T cell development in vitro and in vivo.
- Sara Campinoti
- , Asllan Gjinovci
- & Paola Bonfanti
-
Article
| Open Access
Direct reprogramming of human umbilical vein- and peripheral blood-derived endothelial cells into hepatic progenitor cells
The conditions to induce human hepatic progenitor cells from other cell types are unclear. Here, the authors reprogram human endothelial cells to hepatic progenitor cells by expressing FOXA3, HNF1A and HNF6, capable of giving rise to hepatocytes and cholangiocytes that reconstitute damaged liver tissues on transplantation.
- Hiroki Inada
- , Miyako Udono
- & Atsushi Suzuki
-
Article
| Open Access
Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson’s disease
Induced pluripotent stem cell (iPSC) derived dopaminergic neurons are a promising source for cell-based Parkinson’s disease (PD) therapy. Here the authors report a comprehensive pre-clinical evaluation of the safety and efficacy of dopaminergic progenitors derived from a clinical-grade human iPSC line.
- Daisuke Doi
- , Hiroaki Magotani
- & Jun Takahashi
-
Article
| Open Access
Long-term culture of human pancreatic slices as a model to study real-time islet regeneration
The ability to culture live pancreatic tissue slices for long periods of time would enable longitudinal studies ex vivo. Here the authors culture human and mouse pancreatic slices in a perfluorocarbon-based culture system and show stable endocrine and exocrine function for up to ten days in culture.
- Mirza Muhammad Fahd Qadir
- , Silvia Álvarez-Cubela
- & Juan Domínguez-Bendala
-
Article
| Open Access
Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities
Production of a safe and manufacturable material to mimic anabolic bone for tissue engineering has been hard to achieve to date. Here the authors use a mesenchymal stem cell line generated from induced pluripotent stem cells to produce osteogenic cell-matrix, displaying significant healing properties in mice.
- Eoin P. McNeill
- , Suzanne Zeitouni
- & Carl A. Gregory
-
Article
| Open Access
Endothelialization of arterial vascular grafts by circulating monocytes
Acellular tissue engineered vessels functionalised with VEGF are coated with a layer of endothelial cells after in vivo implantation, but the source of the cells are unknown. Here the authors provide evidence that monocytes expressing VEGF receptors can transdifferentiate into endothelial cells via a macrophage intermediate.
- Randall J. Smith Jr.
- , Bita Nasiri
- & Stelios T. Andreadis
-
Article
| Open Access
Neural cell integration into 3D bioprinted skeletal muscle constructs accelerates restoration of muscle function
3D bioprinting of skeletal muscle using primary human muscle progenitor cells results in correct muscle architecture, but functional restoration in rodent models is limited. Here the authors include human neural stem cells into bioprinted skeletal muscle and observe improved architecture and function in vivo.
- Ji Hyun Kim
- , Ickhee Kim
- & Sang Jin Lee
-
Article
| Open Access
Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities
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
- & Andrés J. García
-
Article
| Open Access
In vivo engineered extracellular matrix scaffolds with instructive niches for oriented tissue regeneration
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
- & Deling Kong
-
Article
| Open Access
Insulin-producing organoids engineered from islet and amniotic epithelial cells to treat diabetes
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
- & Ekaterine Berishvili
-
Article
| Open Access
Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors
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
- & S. Tamir Rashid
-
Article
| Open Access
Artificial cell membrane binding thrombin constructs drive in situ fibrin hydrogel formation
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
- & Adam W. Perriman
-
Article
| Open Access
Generation of pluripotent stem cell-derived mouse kidneys in Sall1-targeted anephric rats
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
- & Masumi Hirabayashi
-
Article
| Open Access
Patterned human microvascular grafts enable rapid vascularization and increase perfusion in infarcted rat hearts
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
- & Ying Zheng
-
Article
| Open Access
Pluripotency and X chromosome dynamics revealed in pig pre-gastrulating embryos by single cell analysis
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
- & Ramiro Alberio
-
Article
| Open Access
High-resolution acoustophoretic 3D cell patterning to construct functional collateral cylindroids for ischemia therapy
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
- & Hyungsuk Lee
-
Article
| Open Access
Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors
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
- & Paolo De Coppi
-
Article
| Open Access
AAV vector-mediated in vivo reprogramming into pluripotency
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
- & Dirk Grimm
-
Article
| Open Access
Laminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing
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
- & Jeffrey A. Hubbell
-
Article
| Open Access
Expansion of functional personalized cells with specific transgene combinations
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
- & Tobias May
-
Article
| Open Access
Bioengineering of functional human induced pluripotent stem cell-derived intestinal grafts
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
- & Harald C. Ott
-
Article
| Open Access
Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition
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
- & Lino Ferreira
-
Article
| Open Access
Retinal transplantation of photoreceptors results in donor–host cytoplasmic exchange
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
- & Marius Ader
-
Article
| Open Access
Donor and host photoreceptors engage in material transfer following transplantation of post-mitotic photoreceptor precursors
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
- & R. R. Ali
-
Article
| Open Access
Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs
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
- & Robert T. Tranquillo
-
Article
| Open Access
A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells
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
- & Martin Fussenegger
-
Article
| Open Access
Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting
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
- & Eduardo Marbán
Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2