Use of photosynthetic transgenic cyanobacteria to promote lymphangiogenesis in scaffolds for dermal regeneration

Chávez, Myra N.; Fuchs, Benedikt; Moellhoff, Nicholas; Hofmann, Daniel; Zhang, Lifang; Selão, Tiago Toscano; Giunta, Riccardo E.; Egaña, José Tomás; Nickelsen, Jörg; Schenck, Thilo L.

doi:10.1016/j.actbio.2021.03.033

Cited by 28 publications

(33 citation statements)

References 77 publications

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“…Based on this, photosynthetic therapies aim to generate a local symbiotic relationship between animal and photosynthetic cells where, in the presence of light, both metabolisms could be coupled with each other ( Chávez et al, 2020 ). This approach has been described by our group in recent in vitro ( Hopfner et al, 2014 ; Centeno-Cerdas et al, 2018 ; Chávez et al, 2021 ) and in vivo ( Schenck et al, 2015 ; Chávez et al, 2016 ) studies, and further confirmed by other independent groups, highlighting its potential application in several medical fields, including tissue engineering and regeneration ( Yamaoka et al, 2012 ; Evron et al, 2015 ; Haraguchi et al, 2017 ; Chen et al, 2020 ), heart ischemia ( Cohen et al, 2017 ), and tumor treatment ( Huo et al, 2020 ; Liu et al, 2020 ; Qiao et al, 2020 ). Moreover, an ongoing clinical trial is confirming its safety for tissue regeneration in humans ( Obaíd et al (2021) accepted for publication.…”

Section: Introductionsupporting

confidence: 71%

“…In this proof-of-concept study, we demonstrate the feasibility to incorporate photosynthetic microorganisms in organ perfusion solutions to provide an alternative intravascular source of oxygen to isolated organs. This concept is based on our previous research in implantable photosynthetic biomaterials ( Hopfner et al, 2014 ; Schenck et al, 2015 ; Chávez et al, 2016 ; Chávez et al, 2021 ; Centeno-Cerdas et al, 2018 ), and could potentially generate a new physiological state of normoxic ischemia , where the lack of blood supply may not necessarily trigger hypoxia. The use of photosynthetic microorganisms as local oxygen factories may have significant advantages compared to the standard approaches.…”

Section: Discussionmentioning

confidence: 99%

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Development of a Novel Perfusable Solution for ex vivo Preservation: Towards Photosynthetic Oxygenation for Organ Transplantation

Veloso-Giménez

Escamilla

Necuñir

et al. 2021

Front. Bioeng. Biotechnol.

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Oxygen is the key molecule for aerobic metabolism, but no animal cells can produce it, creating an extreme dependency on external supply. In contrast, microalgae are photosynthetic microorganisms, therefore, they are able to produce oxygen as plant cells do. As hypoxia is one of the main issues in organ transplantation, especially during preservation, the main goal of this work was to develop the first generation of perfusable photosynthetic solutions, exploring its feasibility for ex vivo organ preservation. Here, the microalgae Chlamydomonas reinhardtii was incorporated in a standard preservation solution, and key aspects such as alterations in cell size, oxygen production and survival were studied. Osmolarity and rheological features of the photosynthetic solution were comparable to human blood. In terms of functionality, the photosynthetic solution proved to be not harmful and to provide sufficient oxygen to support the metabolic requirement of zebrafish larvae and rat kidney slices. Thereafter, isolated porcine kidneys were perfused, and microalgae reached all renal vasculature, without inducing damage. After perfusion and flushing, no signs of tissue damage were detected, and recovered microalgae survived the process. Altogether, this work proposes the use of photosynthetic microorganisms as vascular oxygen factories to generate and deliver oxygen in isolated organs, representing a novel and promising strategy for organ preservation.

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Section: Introductionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Development of a Novel Perfusable Solution for ex vivo Preservation: Towards Photosynthetic Oxygenation for Organ Transplantation

Veloso-Giménez

Escamilla

Necuñir

et al. 2021

Front. Bioeng. Biotechnol.

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“…72.5 µE m −2 s −1 ) (23,24). This particular strain of C. reinhardtii was chosen because our preliminary data showed its safety in in vitro and in vivo settings (13)(14)(15)(16). Afterwards, photosynthetic scaffolds were fabricated following our previously optimized protocols, with minor modifications (14).…”

Section: Photosynthetic Scaffold Fabricationmentioning

confidence: 99%

“…This approach was then validated in vivo in full thickness animal skin defects, demonstrating its safety and proposing that such oxygen-producing biomaterials could be a promising platform toward autotrophic engineered tissues ( 14 ). In addition to targeted oxygen delivery, photosynthetic microalgae engineered to release recombinant growth factors in situ demonstrated novel utility as vehicles for gene therapies in tissue regeneration in vivo ( 15 , 16 ). These developments led to the generation of photosynthetic sutures for local and controlled delivery of oxygen and recombinant growth factors in wounds ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

A First in Human Trial Implanting Microalgae Shows Safety of Photosynthetic Therapy for the Effective Treatment of Full Thickness Skin Wounds

et al. 2021

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Insufficient oxygen supply represents a relevant issue in several fields of human physiology and medicine. It has been suggested that the implantation of photosynthetic cells can provide oxygen to tissues in the absence of a vascular supply. This approach has been demonstrated to be successful in several in vitro and in vivo models; however, no data is available about their safety in human patients. Here, an early phase-1 clinical trial (ClinicalTrials.gov identifier: NCT03960164, https://clinicaltrials.gov/ct2/show/NCT03960164) is presented to evaluate the safety and feasibility of implanting photosynthetic scaffolds for dermal regeneration in eight patients with full-thickness skin wounds. Overall, this trial shows that the presence of the photosynthetic microalgae Chlamydomonas reinhardtii in the implanted scaffolds did not trigger any deleterious local or systemic immune responses in a 90 days follow-up, allowing full tissue regeneration in humans. The results presented here represent the first attempt to treat patients with photosynthetic cells, supporting the translation of photosynthetic therapies into clinics.Clinical Trial Registration:www.clinicaltrials.gov/ct2/show/NCT03960164, identifier: NCT03960164.

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“…Enhanced lymphangiogenesis (lymphatic vessel formation and expansion) has been shown to accelerate inflammation resolution [13]. Lymphangiogenesis is being considered as an effective therapeutic target beneficial for chronic wound healing [18][19][20]. For example, gene therapy approaches aiming at promoting lymphangiogenesis have been shown to significantly reduce chronic inflammation of the skin and accelerate the healing of wounds in diabetic mice [21,22].…”

Section: Introductionmentioning

confidence: 99%

Cerium-Containing Bioactive Glasses Promote In Vitro Lymphangiogenesis

Xie

Sha

et al. 2022

Pharmaceutics

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The lymphatic system is crucial for the regeneration of many tissues due to its fundamental role in immune cell trafficking, protein transport, and tissue homeostasis maintenance. Strategies stimulating lymphangiogenesis can provide new therapeutic approaches for tissue repair and regeneration (e.g., chronic wound healing). Here, we explored the effects of cerium-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) on lymphangiogenesis. The results showed that the extracts of Ce-MBGNs (1, 5, or 10 wt/v%) were non-cytotoxic toward lymphatic endothelial cells (LECs), while they enhanced the proliferation of LECs. Moreover, as evidenced by the scratch wound healing and Transwell migration assays, conditioned media containing the extract of Ce-MBGNs (1 wt/v%) could enhance the migration of LECs in comparison to the blank control and the media containing vascular endothelial growth factor-C (VEGF-C, 50 ng/mL). Additionally, a tube-formation assay using LECs showed that the extract of Ce-MBGNs (1 wt/v%) promoted lymphatic vascular network formation. Western blot results suggested that Ce-MBGNs could induce lymphangiogenesis probably through the HIF-1α/VEGFR-3 pathway. Our study for the first time showed the effects of Ce-MBGNs on stimulating lymphangiogenesis in vitro, highlighting the potential of Ce-MBGNs for wound healing.

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Use of photosynthetic transgenic cyanobacteria to promote lymphangiogenesis in scaffolds for dermal regeneration

Cited by 28 publications

References 77 publications

Development of a Novel Perfusable Solution for ex vivo Preservation: Towards Photosynthetic Oxygenation for Organ Transplantation

Development of a Novel Perfusable Solution for ex vivo Preservation: Towards Photosynthetic Oxygenation for Organ Transplantation

A First in Human Trial Implanting Microalgae Shows Safety of Photosynthetic Therapy for the Effective Treatment of Full Thickness Skin Wounds

Cerium-Containing Bioactive Glasses Promote In Vitro Lymphangiogenesis

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