Nicholas Wragg - Academia.edu (original) (raw)
Papers by Nicholas Wragg
Molecular Neurobiology, 2019
Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to ... more Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer's disease is characterised by the accumulation of amyloid-beta plaques and hyperphosphorylated tau in the brain causing a progressive decline in cognitive impairment. Small non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. A systematic review was conducted to extract all miRNA found to be significantly deregulated in the peripheral blood. These deregulated miRNAs were cross-referenced against the miRNAs deregulated in the brain at Braak Stage III. This resulted in a panel of 10 miRNAs (hsa-mir-107, hsa-mir-26b, hsa-mir-30e, hsa-mir-34a, hsa-mir-485, hsa-mir200c, hsa-mir-210, hsa-mir-146a, hsa-mir-34c, and hsa-mir-125b) hypothesised to be deregulated early in Alzheimer's disease, nearly 20 years before the onset of clinical symptoms. After network analysis of the 10 miRNAs, they were found to be associated with the immune system, cell cycle, gene expression, cellular response to stress, neuron growth factor signalling, wnt signalling, cellular senescence, and Rho GTPases.
Supplementary files for article Cryopreservation of mesenchymal stem cells using medical grade ic... more Supplementary files for article Cryopreservation of mesenchymal stem cells using medical grade ice nucleation inducer. Mesenchymal stem cells (MSCs) can differentiate into multiple different tissue lineages and have favourable immunogenic potential making them an attractive prospect for regenerative medicine. As an essential part of the manufacturing process, preservation of these cells whilst maintaining potential is of critical importance. An uncontrolled area of storage remains the rate of change of temperature during freezing and thawing. Controlled-rate freezers attempted to rectify this; however, the change of phase from liquid to solid introduces two extreme phenomena; a rapid rise and a rapid fall in temperature in addition to the intended cooling rate (normally -1 °C/min) as a part of the supercooling event in cryopreservation. Nucleation events are well known to initiate the freezing transition although their active use in the form of ice nucleation devices (IND) are in th...
This is an abstract of a conference paper presented at the Tissue and Cell Engineering Society (T... more This is an abstract of a conference paper presented at the Tissue and Cell Engineering Society (TCES) meeting 2015, University of Southampton, 19-21 July. This is an Open Access Article. It is published by European Cells & Materials Ltd under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/by-sa/4.0/
This is a conference abstract presented at the Tissue and Cell Engineering Society (TCES) meeting... more This is a conference abstract presented at the Tissue and Cell Engineering Society (TCES) meeting 23rd - 25th July 2013, Cardiff Institute of Tissue Engineering and Repair (CITER), Cardiff University. This is an Open Access Article. It is published by European Cells & Materials Ltd under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/by-sa/4.0/
This is an abstract of a conference paper presented at the Tissue and Cell Engineering Society (T... more This is an abstract of a conference paper presented at the Tissue and Cell Engineering Society (TCES) meeting 2014, Newcastle University. This is an Open Access Article. It is published by European Cells & Materials Ltd under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/by-sa/4.0/
The widening gap between organ availability and need is resulting in a worldwide crisis, particul... more The widening gap between organ availability and need is resulting in a worldwide crisis, particularly concerning kidney transplantation. Regenerative medicine options are becoming increasingly advanced and are taking advantage of progress in novel manufacturing techniques, including 3D bioprinting, to deliver potentially viable alternatives. Cell-integrated and wearable artificial kidneys aim to create convenient and efficient systems of filtration and restore elements of immunoregulatory function. Whilst preliminary clinical trials demonstrated promise, manufacturing and trial design issues and identification of suitable and sustainable cell sources have shown that more development is required for market progression. Tissue engineering and advances in biomanufacturing techniques offer potential solutions for organ shortages; however, due to the complex kidney structure, previous attempts have fallen short. With the recent development and progression of 3D bioprinting, cell position...
Pre-clinical studies are a necessary step in the process of material and drug testing. For this, ... more Pre-clinical studies are a necessary step in the process of material and drug testing. For this, high-throughput monolayer cell cultures are conducted followed by in vivo animal experiments. However, animal use is ethically questionable and in many cases yields misleading results. In vitro three dimensional (3D) tissue engineered (TE) structures have been shown to better represent in vivo tissue morphology and biochemical pathways than monolayer cultures and are less ethically questionable than animal models. Therefore, an in vitro biomimetic musculoskeletal junction (MSKjct) is required as a more relevant pre-clinical testbed. This thesis describes the steps taken to co-culture 3D TE skeletal muscle and bone models as a material testbed and towards an in vitro MSKjct. [Continues.]
This is an abstract of a conference paper presented at the Advancing Tissue and Regenerative Engi... more This is an abstract of a conference paper presented at the Advancing Tissue and Regenerative Engineering in UK Medicine (ATREUM) 2017.
Molecular Therapy - Methods & Clinical Development
SN Comprehensive Clinical Medicine
The prevalence of the rotator cuff (RC) tears is ~ 21% in the general population, with higher inc... more The prevalence of the rotator cuff (RC) tears is ~ 21% in the general population, with higher incidences in individuals over 50. Irrespective of surgical repair techniques employed, re-tear rates are alarmingly high, indicating the need for improvement to the current treatment methods. A method that has recently increased in popularity is the administration of platelet-rich-plasma (PRP), as it has been proposed to significantly encourage and improve healing in a plethora of musculoskeletal tissues, although experimental conditions and results are often variable. This review aims to critically evaluate current literature concerning the use of PRP, specifically for the treatment of RC tears. There are ongoing conflicts debating the effectiveness of PRP to treat RC tears; with literature both in favour and against its use either having profound methodological weaknesses and/or limited applicability to most individuals with RC tears. There are numerous factors that may influence effecti...
Current Osteoporosis Reports
Purpose of Review The treatment of non-union fractures represents a significant challenge for ort... more Purpose of Review The treatment of non-union fractures represents a significant challenge for orthopaedic surgeons. In recent years, biologic agents have been investigated and utilised to support and improve bone healing. Among these agents, platelet-rich plasma (PRP) is an emerging strategy that is gaining popularity. The aim of this review is to evaluate the current literature regarding the application and clinical effectiveness of PRP injections, specifically for the treatment of non-union fractures. Recent Findings The majority of published studies reported that PRP accelerated fracture healing; however, this evidence was predominantly level IV. The lack of randomised, clinical trials (level I–II evidence) is currently hampering the successful clinical translation of PRP as a therapy for non-union fractures. This is despite the positive reports regarding its potential to heal non-union fractures, when used in isolation or in combination with other forms of treatment. Summary Fut...
International Journal of Molecular Sciences
Mesenchymal stem cells (MSCs) can differentiate into multiple different tissue lineages and have ... more Mesenchymal stem cells (MSCs) can differentiate into multiple different tissue lineages and have favourable immunogenic potential making them an attractive prospect for regenerative medicine. As an essential part of the manufacturing process, preservation of these cells whilst maintaining potential is of critical importance. An uncontrolled area of storage remains the rate of change of temperature during freezing and thawing. Controlled-rate freezers attempted to rectify this; however, the change of phase from liquid to solid introduces two extreme phenomena; a rapid rise and a rapid fall in temperature in addition to the intended cooling rate (normally −1 °C/min) as a part of the supercooling event in cryopreservation. Nucleation events are well known to initiate the freezing transition although their active use in the form of ice nucleation devices (IND) are in their infancy in cryopreservation. This study sought to better understand the effects of ice nucleation and its active in...
Knee Surgery, Sports Traumatology, Arthroscopy
Purpose This review aimed to evaluate the efficacy of intra-articular injections of bone marrow d... more Purpose This review aimed to evaluate the efficacy of intra-articular injections of bone marrow derived mesenchymal stem cells (BM-MSCs) for the treatment of knee osteoarthritis (KOA). Methods This narrative review evaluates recent English language clinical data and published research articles between 2014 and 2019. Key word search strings of (((“bone marrow-derived mesenchymal stem cell” OR “bone marrow mesenchymal stromal cell” OR “bone marrow stromal cell”)) AND (“osteoarthritis” OR “knee osteoarthritis”)) AND (“human” OR “clinical”))) AND “intra-articular injection” were used to identify relevant articles using PMC, Cochrane Library, Web Of Science and Scopus databases. Results Pre-clinical studies have demonstrated successful, safe and encouraging results for articular cartilage repair and regeneration. This is concluded to be due to the multilineage differential potential, immunosuppressive and self-renewal capabilities of BM-MSCs, which have shown to augment pain and improve ...
Biotechnology and Bioengineering
Renal Replacement Therapy
Cell and Tissue Research
Osteoarthritis (OA) is a degenerative disease involving joint damage, an inadequate healing respo... more Osteoarthritis (OA) is a degenerative disease involving joint damage, an inadequate healing response and progressive deterioration of the joint architecture that commonly affects the knee and/or hip joints. It is a major world public health problem and is predicted to increase rapidly with an ageing population and escalating rate of obesity. Autologous blood-derived products possess much promise in the repair and regeneration of tissue and have important roles in inflammation, angiogenesis, cell migration and metabolism in pathological conditions, including OA. Utilising platelet-rich plasma (PRP) to treat tendon, ligament and skeletal muscle has shown variable results across many studies with the current evidence base for the efficacy of PRP in treating sports injuries remaining inconclusive. More uniformly positive results have been observed by various studies for PRP in OA knee in comparison to hyaluronic acid, other intra-articular injections and placebo than in other musculoskeletal tissue. However, methodological concerns as well as satisfactory PRP product classification prevent the true characterisation of this treatment. Thus, further research is required to investigate how leukocyte inclusion, activation and platelet concentration affect therapeutic efficacy. Furthermore, the optimisation of timing, dosage, volume, frequency and rehabilitation strategies need to be ascertained. For knee OA management, these concerns must be addressed before this promising treatment can be widely implemented.
SN Comprehensive Clinical Medicine
Rotator cuff injuries (RCIs) present a major health problem due to high incidences of degenerativ... more Rotator cuff injuries (RCIs) present a major health problem due to high incidences of degenerative tears greater than 3 cm and prevalence of re-tears following surgical procedures. Since healing and functional restoration relies upon bone ingrowth into the tendon, it is hypothesised that sustained delivery of osteoinductive factors including bone morphogenetic proteins (BMPs), specifically BMP2-7, may significantly improve RCI tendon-bone healing. Here, growth factor candidates and delivery mechanisms are reviewed, specifically for improved RCI healing through enhanced bone ingrowth. In addition to BMPs, other potentially osteogenic factors including platelet-derived growth factors (PDGF), fibroblast growth factor (FGF), transforming growth beta isoforms (TGF-β1 and TGF-3) and parathyroid hormone (PTH) are evaluated since they can induce bone formation at the healing tendon attachment site. Several challenges must be addressed prior to clinical translation. The majority of published studies utilise in vivo animal models. In general, BMP-7 demonstrates a stronger stimulating effect when compared to BMP-2; the reported effectiveness of BMP-2 is often conflicting. Alternative factors, including PDGF and PTH, also demonstrate potential for assisting bone growth in enthesis healing. The use of sustained and biomimetic delivery systems appears to have the greatest positive effects. Some studies have demonstrated a dose-dependent effect, in conjunction with varying age, indicating that stratified therapies could be a viable solution for RCI healing. To adequately resolve potential treatments for RCI, further expanded and correlated animal trials must be undertaken, and indicative human trials are required with consideration of surgical and patient-specific influences.
Molecular Neurobiology, 2019
Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to ... more Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer's disease is characterised by the accumulation of amyloid-beta plaques and hyperphosphorylated tau in the brain causing a progressive decline in cognitive impairment. Small non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. A systematic review was conducted to extract all miRNA found to be significantly deregulated in the peripheral blood. These deregulated miRNAs were cross-referenced against the miRNAs deregulated in the brain at Braak Stage III. This resulted in a panel of 10 miRNAs (hsa-mir-107, hsa-mir-26b, hsa-mir-30e, hsa-mir-34a, hsa-mir-485, hsa-mir200c, hsa-mir-210, hsa-mir-146a, hsa-mir-34c, and hsa-mir-125b) hypothesised to be deregulated early in Alzheimer's disease, nearly 20 years before the onset of clinical symptoms. After network analysis of the 10 miRNAs, they were found to be associated with the immune system, cell cycle, gene expression, cellular response to stress, neuron growth factor signalling, wnt signalling, cellular senescence, and Rho GTPases.
Supplementary files for article Cryopreservation of mesenchymal stem cells using medical grade ic... more Supplementary files for article Cryopreservation of mesenchymal stem cells using medical grade ice nucleation inducer. Mesenchymal stem cells (MSCs) can differentiate into multiple different tissue lineages and have favourable immunogenic potential making them an attractive prospect for regenerative medicine. As an essential part of the manufacturing process, preservation of these cells whilst maintaining potential is of critical importance. An uncontrolled area of storage remains the rate of change of temperature during freezing and thawing. Controlled-rate freezers attempted to rectify this; however, the change of phase from liquid to solid introduces two extreme phenomena; a rapid rise and a rapid fall in temperature in addition to the intended cooling rate (normally -1 °C/min) as a part of the supercooling event in cryopreservation. Nucleation events are well known to initiate the freezing transition although their active use in the form of ice nucleation devices (IND) are in th...
This is an abstract of a conference paper presented at the Tissue and Cell Engineering Society (T... more This is an abstract of a conference paper presented at the Tissue and Cell Engineering Society (TCES) meeting 2015, University of Southampton, 19-21 July. This is an Open Access Article. It is published by European Cells & Materials Ltd under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/by-sa/4.0/
This is a conference abstract presented at the Tissue and Cell Engineering Society (TCES) meeting... more This is a conference abstract presented at the Tissue and Cell Engineering Society (TCES) meeting 23rd - 25th July 2013, Cardiff Institute of Tissue Engineering and Repair (CITER), Cardiff University. This is an Open Access Article. It is published by European Cells & Materials Ltd under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/by-sa/4.0/
This is an abstract of a conference paper presented at the Tissue and Cell Engineering Society (T... more This is an abstract of a conference paper presented at the Tissue and Cell Engineering Society (TCES) meeting 2014, Newcastle University. This is an Open Access Article. It is published by European Cells & Materials Ltd under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/by-sa/4.0/
The widening gap between organ availability and need is resulting in a worldwide crisis, particul... more The widening gap between organ availability and need is resulting in a worldwide crisis, particularly concerning kidney transplantation. Regenerative medicine options are becoming increasingly advanced and are taking advantage of progress in novel manufacturing techniques, including 3D bioprinting, to deliver potentially viable alternatives. Cell-integrated and wearable artificial kidneys aim to create convenient and efficient systems of filtration and restore elements of immunoregulatory function. Whilst preliminary clinical trials demonstrated promise, manufacturing and trial design issues and identification of suitable and sustainable cell sources have shown that more development is required for market progression. Tissue engineering and advances in biomanufacturing techniques offer potential solutions for organ shortages; however, due to the complex kidney structure, previous attempts have fallen short. With the recent development and progression of 3D bioprinting, cell position...
Pre-clinical studies are a necessary step in the process of material and drug testing. For this, ... more Pre-clinical studies are a necessary step in the process of material and drug testing. For this, high-throughput monolayer cell cultures are conducted followed by in vivo animal experiments. However, animal use is ethically questionable and in many cases yields misleading results. In vitro three dimensional (3D) tissue engineered (TE) structures have been shown to better represent in vivo tissue morphology and biochemical pathways than monolayer cultures and are less ethically questionable than animal models. Therefore, an in vitro biomimetic musculoskeletal junction (MSKjct) is required as a more relevant pre-clinical testbed. This thesis describes the steps taken to co-culture 3D TE skeletal muscle and bone models as a material testbed and towards an in vitro MSKjct. [Continues.]
This is an abstract of a conference paper presented at the Advancing Tissue and Regenerative Engi... more This is an abstract of a conference paper presented at the Advancing Tissue and Regenerative Engineering in UK Medicine (ATREUM) 2017.
Molecular Therapy - Methods & Clinical Development
SN Comprehensive Clinical Medicine
The prevalence of the rotator cuff (RC) tears is ~ 21% in the general population, with higher inc... more The prevalence of the rotator cuff (RC) tears is ~ 21% in the general population, with higher incidences in individuals over 50. Irrespective of surgical repair techniques employed, re-tear rates are alarmingly high, indicating the need for improvement to the current treatment methods. A method that has recently increased in popularity is the administration of platelet-rich-plasma (PRP), as it has been proposed to significantly encourage and improve healing in a plethora of musculoskeletal tissues, although experimental conditions and results are often variable. This review aims to critically evaluate current literature concerning the use of PRP, specifically for the treatment of RC tears. There are ongoing conflicts debating the effectiveness of PRP to treat RC tears; with literature both in favour and against its use either having profound methodological weaknesses and/or limited applicability to most individuals with RC tears. There are numerous factors that may influence effecti...
Current Osteoporosis Reports
Purpose of Review The treatment of non-union fractures represents a significant challenge for ort... more Purpose of Review The treatment of non-union fractures represents a significant challenge for orthopaedic surgeons. In recent years, biologic agents have been investigated and utilised to support and improve bone healing. Among these agents, platelet-rich plasma (PRP) is an emerging strategy that is gaining popularity. The aim of this review is to evaluate the current literature regarding the application and clinical effectiveness of PRP injections, specifically for the treatment of non-union fractures. Recent Findings The majority of published studies reported that PRP accelerated fracture healing; however, this evidence was predominantly level IV. The lack of randomised, clinical trials (level I–II evidence) is currently hampering the successful clinical translation of PRP as a therapy for non-union fractures. This is despite the positive reports regarding its potential to heal non-union fractures, when used in isolation or in combination with other forms of treatment. Summary Fut...
International Journal of Molecular Sciences
Mesenchymal stem cells (MSCs) can differentiate into multiple different tissue lineages and have ... more Mesenchymal stem cells (MSCs) can differentiate into multiple different tissue lineages and have favourable immunogenic potential making them an attractive prospect for regenerative medicine. As an essential part of the manufacturing process, preservation of these cells whilst maintaining potential is of critical importance. An uncontrolled area of storage remains the rate of change of temperature during freezing and thawing. Controlled-rate freezers attempted to rectify this; however, the change of phase from liquid to solid introduces two extreme phenomena; a rapid rise and a rapid fall in temperature in addition to the intended cooling rate (normally −1 °C/min) as a part of the supercooling event in cryopreservation. Nucleation events are well known to initiate the freezing transition although their active use in the form of ice nucleation devices (IND) are in their infancy in cryopreservation. This study sought to better understand the effects of ice nucleation and its active in...
Knee Surgery, Sports Traumatology, Arthroscopy
Purpose This review aimed to evaluate the efficacy of intra-articular injections of bone marrow d... more Purpose This review aimed to evaluate the efficacy of intra-articular injections of bone marrow derived mesenchymal stem cells (BM-MSCs) for the treatment of knee osteoarthritis (KOA). Methods This narrative review evaluates recent English language clinical data and published research articles between 2014 and 2019. Key word search strings of (((“bone marrow-derived mesenchymal stem cell” OR “bone marrow mesenchymal stromal cell” OR “bone marrow stromal cell”)) AND (“osteoarthritis” OR “knee osteoarthritis”)) AND (“human” OR “clinical”))) AND “intra-articular injection” were used to identify relevant articles using PMC, Cochrane Library, Web Of Science and Scopus databases. Results Pre-clinical studies have demonstrated successful, safe and encouraging results for articular cartilage repair and regeneration. This is concluded to be due to the multilineage differential potential, immunosuppressive and self-renewal capabilities of BM-MSCs, which have shown to augment pain and improve ...
Biotechnology and Bioengineering
Renal Replacement Therapy
Cell and Tissue Research
Osteoarthritis (OA) is a degenerative disease involving joint damage, an inadequate healing respo... more Osteoarthritis (OA) is a degenerative disease involving joint damage, an inadequate healing response and progressive deterioration of the joint architecture that commonly affects the knee and/or hip joints. It is a major world public health problem and is predicted to increase rapidly with an ageing population and escalating rate of obesity. Autologous blood-derived products possess much promise in the repair and regeneration of tissue and have important roles in inflammation, angiogenesis, cell migration and metabolism in pathological conditions, including OA. Utilising platelet-rich plasma (PRP) to treat tendon, ligament and skeletal muscle has shown variable results across many studies with the current evidence base for the efficacy of PRP in treating sports injuries remaining inconclusive. More uniformly positive results have been observed by various studies for PRP in OA knee in comparison to hyaluronic acid, other intra-articular injections and placebo than in other musculoskeletal tissue. However, methodological concerns as well as satisfactory PRP product classification prevent the true characterisation of this treatment. Thus, further research is required to investigate how leukocyte inclusion, activation and platelet concentration affect therapeutic efficacy. Furthermore, the optimisation of timing, dosage, volume, frequency and rehabilitation strategies need to be ascertained. For knee OA management, these concerns must be addressed before this promising treatment can be widely implemented.
SN Comprehensive Clinical Medicine
Rotator cuff injuries (RCIs) present a major health problem due to high incidences of degenerativ... more Rotator cuff injuries (RCIs) present a major health problem due to high incidences of degenerative tears greater than 3 cm and prevalence of re-tears following surgical procedures. Since healing and functional restoration relies upon bone ingrowth into the tendon, it is hypothesised that sustained delivery of osteoinductive factors including bone morphogenetic proteins (BMPs), specifically BMP2-7, may significantly improve RCI tendon-bone healing. Here, growth factor candidates and delivery mechanisms are reviewed, specifically for improved RCI healing through enhanced bone ingrowth. In addition to BMPs, other potentially osteogenic factors including platelet-derived growth factors (PDGF), fibroblast growth factor (FGF), transforming growth beta isoforms (TGF-β1 and TGF-3) and parathyroid hormone (PTH) are evaluated since they can induce bone formation at the healing tendon attachment site. Several challenges must be addressed prior to clinical translation. The majority of published studies utilise in vivo animal models. In general, BMP-7 demonstrates a stronger stimulating effect when compared to BMP-2; the reported effectiveness of BMP-2 is often conflicting. Alternative factors, including PDGF and PTH, also demonstrate potential for assisting bone growth in enthesis healing. The use of sustained and biomimetic delivery systems appears to have the greatest positive effects. Some studies have demonstrated a dose-dependent effect, in conjunction with varying age, indicating that stratified therapies could be a viable solution for RCI healing. To adequately resolve potential treatments for RCI, further expanded and correlated animal trials must be undertaken, and indicative human trials are required with consideration of surgical and patient-specific influences.