Expression of nAG and Prod-1 in Terminal Phalanx Amputation Stumps of Adult Mice

Al‐Qattan, Mohammad M.; Abd-Alwahed, Mervat M.; Arafah, Maha; Al-Qattan, Ahmed M.; Shier, Medhat K.

doi:10.1097/01.prs.0000479994.27126.4a

Cited by 5 publications

(4 citation statements)

References 12 publications

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“…177,178 Prod1 and nAG and genes suitable for humans have been designed, cloned, and successfully expressed in a distal phalanx model in mice, resulting in a quicker and more mature bony regeneration. 179 The same group previously demonstrated that injection of recombinant nAG protein reduced scar hypertrophy in rabbits 179 and liver fibrosis in rats, 180 supporting the relationship between regenerative mechanisms and antifibrotic mechanisms. Releasing these recombinant proteins in a controlled manner from biomaterial implants may be able to induce a more stable, sustained, and localized regenerative response in mammals.…”

Section: Controlled Immune Responsementioning

confidence: 83%

“…Two regeneration-specific proteins expressed in salamanders are Prod1 and newt-anterior gradient protein (nAG), which are crucial for blastema formation and proliferation of progenitor cells. , Prod1 and nAG and genes suitable for humans have been designed, cloned, and successfully expressed in a distal phalanx model in mice, resulting in a quicker and more mature bony regeneration . The same group previously demonstrated that injection of recombinant nAG protein reduced scar hypertrophy in rabbits and liver fibrosis in rats, supporting the relationship between regenerative mechanisms and antifibrotic mechanisms. Releasing these recombinant proteins in a controlled manner from biomaterial implants may be able to induce a more stable, sustained, and localized regenerative response in mammals.…”

Section: Potential Strategies For Biomaterials Design Inspired By Re...mentioning

confidence: 99%

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Biomaterial Design Inspired by Regenerative Research Organisms

Sapru

Dill

Simmons

2022

ACS Biomater. Sci. Eng.

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The efficacy of implanted biomaterials is largely dependent on the response of the host's immune and stromal cells. Severe foreign body response (FBR) can impede the integration of the implant into the host tissue and compromise the intended mechanical and biochemical function. Many features of FBR, including late-stage fibrotic encapsulation of implants, parallel the formation of fibrotic scar tissue after tissue injury. Regenerative organisms like zebrafish and salamanders can avoid fibrosis after injury entirely, but FBR in these research organisms is rarely investigated because their immune competence is much lower than humans. The recent characterization of a regenerative mammal, the spiny mouse (Acomys), has inspired us to take a closer look at cellular regulation in regenerative organisms across the animal kingdom for insights into avoiding FBR in humans. Here, we highlight how major features of regeneration, such as blastema formation, macrophage polarization, and matrix composition, can be modulated across a range of regenerative research organisms to elucidate common features that may be harnessed to minimize FBR. Leveraging a deeper understanding of regenerative biology for biomaterial design may help to reduce FBR and improve device integration and performance.

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Section: Controlled Immune Responsementioning

confidence: 83%

Section: Potential Strategies For Biomaterials Design Inspired By Re...mentioning

confidence: 99%

Biomaterial Design Inspired by Regenerative Research Organisms

Sapru

Dill

Simmons

2022

ACS Biomater. Sci. Eng.

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“…Regrowth of amputated limbs in salamanders is regulated by the up regulation of expression of the nAG protein in the stump. We described a nAG gene for higher vertebrates (salamanders are lower vertebrates) and showed that the novel nAG protein is a strong inhibitor of scarring of the skin (Al-Qattan et al., 2013d), is an effective method of treating spinal cord injuries in the rat model (Al-Qattan et al., 2017a) and it mediates digital tip regeneration in higher vertebrate ( Al-Qattan et al., 2014, 2016). I am currently working on my ‘nAG Project’ at the CMRC, which will continue as my retirement project.…”

Section: Other Hand Conditionsmentioning

confidence: 99%

My journey in hand surgery: combining patient care, clinical and basic science research

Al‐Qattan

2023

J Hand Surg Eur Vol

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This review is about my clinical and research journey in hand surgery. The journey has been a worthwhile and meaningful one, especially when I felt there were areas I could influence management, whether this be rare cases, common conditions or where a suggested algorithm may be helpful. I also had the unique privilege of working with geneticists, which has resulted in clinical-pathological publications that could influence patient management, as shared from a clinician’s perspective. It is hoped this article will inspire young clinician scientists to pursue a journey of collaboration with other researchers.

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“…nAG expression was found to suppress the expression of collagen in human fibroblasts regardless of the presence of Transforming Growth Factor Beta (TGF β ) [2]. The antifibrotic properties of the nAG protein were later shown in several animal models such as a rabbit model of hypertrophic scar [3], a mouse model of digital tip amputation [4], and a rat spinal cord crush injury model [5]. The antifibrotic effects of nAG on liver fibrosis have not been previously investigated.…”

Section: Introductionmentioning

confidence: 99%

The Use of Antifibrotic Recombinant nAG Protein in a Rat Liver Fibrosis Model

Arafah

Al‐Qattan

Abdulmaged-Ahmed

et al. 2019

BioMed Research International

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Objectives. The “nAG” protein is the key protein mediating the regeneration of amputated limbs in salamanders. The senior author (MMA) developed the original hypothesis that since “nAG” is a “regenerative” protein, it must be also an “antifibrotic’ protein. The antifibrotic properties were later confirmed in a rabbit skin hypertrophic scar model as well as in a rat spinal cord injury model. The aim of this study is to evaluate the potential therapeutic properties of the nAG protein in a rat liver fibrosis model. Methodology. Liver fibrosis was induced using intraperitoneal injections of carbon tetrachloride (CCL4). A total of 45 rats were divided equally into 3 groups: Group I (the control group) received normal saline injections for 8 weeks, Group II received CCL4 for 8 weeks, and Group III received CCL4 and nAG for 8 weeks. At the end of the experiment, the serum levels of 6 proteins (hyaluronic acid, PDGF-AB, TIMP-1, laminin, procollagen III N-terminal peptide, and collagen IV-alpha 1 chain) were measured. Liver biopsies were also taken and the stages of live fibrosis were assessed histologically. Results. The CCL4 treatment resulted in a significant increase in the serum levels of all 6 measured proteins. The nAG treatment significantly reduced these high levels. The degree of liver fibrosis was also significantly reduced in the CCL4/nAG group compared to the CCL4 group. Conclusions. nAG treatment was able to significantly reduce the serum levels of several protein markers of liver fibrosis and also significantly reduced the histological degree of liver fibrosis.

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Expression of nAG and Prod-1 in Terminal Phalanx Amputation Stumps of Adult Mice

Abstract: Injection of nAG and Prod-1 into the footpad will result in their expression in the distal amputation stumps, and this will enhance bone regeneration in the model described.

Cited by 5 publications

References 12 publications

Biomaterial Design Inspired by Regenerative Research Organisms

Biomaterial Design Inspired by Regenerative Research Organisms

My journey in hand surgery: combining patient care, clinical and basic science research

The Use of Antifibrotic Recombinant nAG Protein in a Rat Liver Fibrosis Model

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