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Update on Cancer Related Issues of Mesenchymal Stem Cell-based Therapies
Dechun Wang, Shuguang Wang and Chunmeng Shi
[Abstract] [FULL-TEXT INQUIRY] [PMID: 22329585 PubMed - indexed for MEDLINE] [BSP/CSCRT/E-Pub/00115]


Isolation and phenotypic characterisation of stem cells from late stage osteoarthritic mesenchymal tissues
Luminita Labusca, Georgina Shaw, Paul Botez, Florin Zugun-Eloae, Kaveh Mashayekhi and Frank Barry
[Abstract] [FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00116]


CCR5-targeted hematopoietic stem cell gene approaches for HIV disease: current progress and future prospects
Yu Lai
[Abstract] [FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00117]


Transplantation of Adipose Derived Stem Cells for Peripheral Nerve Regeneration in Sciatic Nerve Defects of the Rat
Ja Hea Gu, Yi Hwa Ji, Eun-Sang Dhong, Dong Hwee Kim and Eul-Sik Yoon
[Abstract] [FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00118]


Editorial: Stem Cell Therapy and Tissue Engineering Applications for Cartilage Regeneration
Malik A and Khan WS
[BSP/CSCRT/E-Pub/00119]


Chondrogenesis and developments in our understanding
Nigel Mabvuure, Sandip Hindocha, Daniel Jordan and Wasim S. Khan
[Abstract] [FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00120]


Chondrogenic differentiation of adult MSCs
Griffin M, Hindocha S and Khan WS
[Abstract] [FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00121]


Expression of the Two Pore Domain Potassium Channel TREK-1 in Human Intervertebral Disc Cells
Pankaj Sharma, Stephen Hughes, Alicia El Haj and Nicola Maffulli
[Abstract] [FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00122]


Stem Cells From Umbilical Cord And Placenta For Musculoskeletal Tissue Engineering
Umile Giuseppe Longo, Mattia Loppini, Alessandra Berton, Luca La Verde, Wasim S Khan and Vincenzo Denaro
[Abstract] [FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00123]


The Effects Of Ageing On Proliferation Potential, Differentiation Potential And Cell Surface Characterisation Of Human Mesenchymal Stem Cells
Fossett E, Khan WS, Pastides P and Adesida AB
[Abstract] [FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00124]


The Role Of Bioreactors In Cartilage Tissue Engineering
Nigel Mabvuure, Sandip Hindocha and Wasim S. Khan
[Abstract] [FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00125]


Endothelial Progenitor Cells (Epcs) And Mesenchymal Stem Cells (Mscs) In Bone Healing
Nikolaos C Keramaris, Sarandos Kaptanis, Helen Lucy Moss, Mattia Loppini, Spyridon Pneumaticos and Nicola Maffulli
[Abstract] [FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00126]


Evaluation of biological protein-based collagen scaffolds in cartilage and musculoskeletal tissue engineering- A systematic Review of the Literature
Mafi P, Hindocha S, Mafi R and Khan WS
[Abstract] [FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00127]



Abstracts


Update on Cancer Related Issues of Mesenchymal Stem Cell-based Therapies
Dechun Wang, Shuguang Wang and Chunmeng Shi
[FULL-TEXT INQUIRY] [PMID: 22329585 PubMed - indexed for MEDLINE] [BSP/CSCRT/E-Pub/00115]

Mesenchymal stem cells (also known as multipotent stromal cells, MSCs) are considered as promising candidate cells for stem cell-based therapy. However, the applications of MSCs are facing controversial concerns of potential tumorigenic risks. There is also increasing evidence that MSCs may play a modulatory role in the development and progression of tumors. MSCs have the potential to migrate to tumor sites and promote tumor cell proliferation, invasion and metastasis. In addition to these risks, MSCs also have shown to be an attractive target for gene/cell-mediated anti-tumor therapy. These complicated behaviors of MSCs in cancer warrant furthre study to evaluate the benefits of MSCs treatment and the long-term risk of tumor origin or incidence from MSCs under different pathological conditions.
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Isolation and phenotypic characterisation of stem cells from late stage osteoarthritic mesenchymal tissues
Luminita Labusca, Georgina Shaw, Paul Botez, Florin Zugun-Eloae, Kaveh Mashayekhi and Frank Barry
[FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00116]

Introduction: Osteoarthritis represents an increasing health issue worldwide. Regenerative medicine (RM) has raised the hope for introducing revolutionary therapies in clinical practice. Detection of autologus cell sources can improve accessibility to RM strategies.

Objectives: to assess the presence and biological potential of mesehchymal stem cells in three tissues (subchondral bone, synovial layer, periarticular adipose tissue) in late stages osteoarthritic patients.

Material and Methods: samples were collected from subjects undergoing total knee replacement (TKR).. MSCs were isolated and cultured in complete αMEM with β FGF. Cell morphology and growth potential was assessed. Flow cytometry was used for detection of cell surface markers. Quantitative and qualitative assessment of differentiation potential towards three mesenchymal lineages (osteogenesis adipogenesis chondrogenesis) was performed. Time lapse life cell imaging of nondiferentiated cells over 24 hours period was used to determine cell kinetics.

Results: mesenchymal cells derived from all donors and tissue types showed morphology, growth and surface cell markers associated with stemness. All cell types underwent differentiation toward three mesenchymal lineages with significant differences between tissues of origin, not between donors. Cell kinetics, as derived from life imaging records, was variable with tissue of origin, significant higher for adipose derived MSCS.

Conclusion: Human late stage OA mesenchymal tissues, contain progenitors with proliferative and differentiation potential of MSCs. These populations can be used for research and autologus regenerative therapies. Further comparative studies with age matched non OA samples has the potential of contributing to deepening knowledge about disease occurrence and progression.
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CCR5-targeted hematopoietic stem cell gene approaches for HIV disease: current progress and future prospects
Yu Lai
[FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00117]

Despite substantial progress that has been made in understanding many aspects regarding biology and pathogenesis of human immunodeficiency virus type 1 (HIV-1), there is currently no vaccine or curative treatment available. HIV-1 continues to be a major global health problem. In this regard, new strategies are required for promoting a complete immune reconstitution and eradicating the virus from the body. The rationale for the use of hematopoietic stem cell (HSC)-based gene therapy against HIV infection is that, after transplantation, genetically modified HSCs carrying anti-HIV transgenes would engraft, divide and differentiate into large numbers of mature myeloid and lymphoid cells that express antiviral genes and thus are protected from HIV invasion or productive replication. HIV-1 attachment to susceptible cells involves binding of gp120 to CD4 receptor and subsequently to a HIV co-receptor, either CCR5 or CXCR4. The pivotal role of CCR5 in HIV-1 acquisition and disease progression has been established by the discovery of a naturally occurring 32-bp deletion in CCR5 (CCR5Δ32) which generates a nonfunctional gene product. Homozygosity for CCR5Δ32 confers profound resistance against HIV infection, and heterozygous mutation that induces a decrease in CCR5 surface expression is associated with lower plasma viral load and delayed progression to AIDS. This, together with the fact of R5 dominance during the acute and asymptomatic phase suggests that CCR5 is an attractive target for HIV gene therapeutics. The present review addresses recent advances of CCR5-targeted HSC gene approaches to treat HIV infection, discusses the future prospects and postulates potential strategies in the field.
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Transplantation of Adipose Derived Stem Cells for Peripheral Nerve Regeneration in Sciatic Nerve Defects of the Rat
Ja Hea Gu, Yi Hwa Ji, Eun-Sang Dhong, Dong Hwee Kim and Eul-Sik Yoon
[FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00118]

Tissue engineering approaches for promoting the repair of peripheral nerve injuries have focused on cell-based therapies involving Adipose-derived stem cells (ASCs). The authors evaluated the effects of undifferentiated ASCs and of neurally differentiated ASCs on the regenerating abilities of peripheral nerves. We hope that this would demonstrate the feasibility of using adipose derived stem cells for peripheral nerve regeneration and provide clues regarding the use of adipose-derived stem cells.

ASCs were isolated and cultured then the cells were cultured with neuronal induction agents for neural differentiation. ASCs and neurally differentiated ASCs were transplanted into sciatic nerve defects. After 12 weeks, the number and diameter of the myelinated fibers are measured and nerve conduction study was done.

The extent of regeneration of myelinated fibers in the neurally differentiated ASCs transplanted group was greater than that in the ASCs transplanted group or the control group. However, thickness of myelin sheath and diameter of nerve fibers in the ASCs transplanted group were greater than that in the neutrally differentiated ASCs transplanted group or the control group. Nerve conduction study showed good recovery in the neurally differentiated ASCs transplanted groups.

Muscles can atrophy and contract if denervation has started. It would be difficult to recover muscle function even if the nerve was reinnervated. Therefore, although neurally differentiated ASCs were found to have a greater functional effect than non-differentiated ASCs, time constraint is important when considering a method of ASCs transplantation.
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Editorial: Stem Cell Therapy and Tissue Engineering Applications for Cartilage Regeneration
Malik A and Khan WS
[BSP/CSCRT/E-Pub/00119]

Cartilage disorders and injuries range from acute injuries to chronic, debilitating diseases and significantly affect an individual’s well-being. This results in a significant disease burden on society as a whole. In recent years there has been great interest in the cell-based treatment strategies and the potential of stem cell-based treatment options for the repair of cartilage. Being an avascular, aneural and alymphatic tissue, it is well suited to stem cell and tissue engineering applications. In this issue, we look at stem cells from various sources and discuss their isolation, proliferation and differentiation. We also consider the associated use of bioreactors, biomaterials, scaffolds and growth factors. We cover the use of stem cell applications for cartilage, and discuss the basic sciences, pre-clinical and clinical studies in the field.

In this series we discuss advances in our understanding of chondrogenesis. Conditions affecting cartilage through damage or age-related degeneration pose significant challenges to individual patients and their healthcare systems. The disease burden will rise in the future as life expectancy increases. This has resulted in vigorous efforts to develop novel therapies to meet current and future needs. Due to the limited regenerative capacity of cartilage, in vitro tissue engineering techniques have emerged as the favoured technique by which to develop replacements. Tissue engineering is mainly concerned with developing cartilage replacements in the form of chondrocyte suspensions and three-dimensional scaffolds seeded with chondrocytes. One major limiting factor in the development of clinically useful cartilage constructs is our understanding of the process by which cartilage is formed, chondrogenesis. For example, techniques of culturing chondrocytes in vitro have been used for decades, resulting in chondrocyte-like cells which produce an extracellular matrix of similar composition to native cartilage, but with inferior physical properties. It has now been realised that one aspect of chondrogenesis which had been ignored was the physical context in which cartilage exists in vivo. This has resulted in the development of bioreactor systems which aim to introduce various physical stresses to engineered cartilage in a controlled environment. This has resulted in some improvements in the quality of tissue engineered cartilage. This is but one example of how the knowledge of chondrogenesis has been translated into research practice. In this series, we review what is currently known about the process of chondrogenesis and discusses how this knowledge can be applied to tissue engineering.

Chondrogenesis is a vital part of adult life, as cartilage is important not only for articulation of joints but also maintenance functions of the body. Chondrogenesis is a five way process of intricate events controlled by specific genes and cell-cell interactions which has been documented over recent years. This review highlights the current literature regarding the process of endochondral ossification and covers the different level of control at agent level. Due to the proliferative nature of chondrogenesis and using chondrocytes for self renewal and repair, current research involves finding ways in which to improve and replicate expansion of chondrocytes. In this series, we summarise ways in which ex vitro expansion can be manipulated using growth factors, external sources and scaffolds.

There is much interest in intervertebral disc degeneration and, in a research paper included in this series, we explore role of the TREK-1 ion channel. Potassium channels play a major role in intracellular homeostasis and regulation of cell volume. Intervertebral disc cells respond to mechanical loading in a complex manner. Mechanical loading may play a role in disc degeneration. In lumbar intervertebral disc samples from five patients, cells from the nucleus pulposus and the annulus fibrosus were investigated to determine RNA expression and protein expression. Analysis of mRNA expression by RT-PCR demonstrated that TREK 1 was expressed by nucleus pulposus and annulus fibrosus cells. Currently, TREK-1 is the only potassium channel known to be activated by intracellular acidosis, and responds to mechanical and chemical stimuli. Whilst the precise role of potassium channels in cellular homeostasis remains to be determined, TREK-1 may be important to protect disc cells against ischaemic damage, and subsequent disc degeneration, and may also play a role in effecting mechanotransduction. Further research is required to fully elucidate the role of the TREK-1 ion channel in intervertebral disc cells.

Mesenchymal stem cells isolated from amnion/amniotic fluid, umbilical cord blood, placental tissue, umbilical cord vein and the Wharton’s Jelly are promising candidate for musculoskeletal tissue engineering of bone and cartilage tissues. These sources are explored in a review paper. The extracorporeal nature of this source avoids the ethical concerns that plague the isolation of embryonic stem cells. Moreover, the harvesting does not require the invasive and discomfort extraction procedures as well as patient risks that attend adult stem cell isolation. Current preclinical studies support the application of these cell-based therapies for the regeneration of musculoskeletal tissues. A literature review focuses on actual knowledge and the future perspectives of the stem cells deriving from umbilical cord and placenta for musculoskeletal tissue engineering. Although mesenchymal stem cells have a great capacity for use in regenerative medicine and other clinical applications, one questions creating curiosity of their use is how they are affected by ageing. As we now live within an ageing population, the prevalence of age related disorders is increasing, so it is important to investigate how effectively mesenchymal stem, cells from older patients can be expanded and differentiated in vitro before their use in autologous transplantation. We include in our series a paper that looks at how ageing effects proliferation potential, differentiation potential and cell surface characterisation of human mesenchymal stem cells.

We discuss the role of bioreactors in cartilage tissue engineering. Cartilage tissue engineering is concerned with developing in vitro cartilage implants that closely match the properties of native cartilage, for eventual implantation to replace damaged cartilage.  The three components to cartilage tissue engineering are cell source, such as in vitro expanded autologous chondrocytes or mesenchymal progenitor cells, a scaffold onto which the cells are seeded and a bioreactor which attempts to recreate the in vivo physicochemical conditions in which cartilage develops. Although much progress has been made towards the goal of developing clinically useful cartilage constructs, current constructs have inferior physicochemical properties than native cartilage. One of the reasons for this is the neglect of mechanical forces in cartilage culture.  Bioreactors have been defined as devices in which biological or biochemical processes can be re-enacted under controlled conditions e.g. pH, temperature, nutrient supply, oxygen tension and waste removal. In the review, we detail the role of bioreactors in the engineering of cartilage, including a discussion of bioreactor designs, current state of the art and future perspectives.

Endothelial Progenitor Cells (EPCs) and other Endothelial Cellular populations (ECs) could constitute a valid alternative to mesenchymal stem cells for musculoskeletal applications. We include in our series a systematic literature review that examines the importance of co-implantation of mesenchymal stem cells and EPCs/ECs for bone healing. The review concludes that ECs could be of value for the treatment of critical size bone defects as they are known to be capable of forming ectopic, vascularised bone. The co-implantation of ECs with mesenchymal stem cells is more intriguing when we take into account the vast array of complex reciprocal interactions between ECs and mesenchymal stem cells.

Lastly we include a systematic literature review that evaluates the biological protein-based collagen scaffolds in cartilage and musculoskeletal tissue engineering. Several criteria were identified as the most desirable characteristics of an ideal scaffold. These state that an ideal scaffolds needs to be biodegradable, possess mechanical strength, be highly porous, biocompatible, non-cytotoxic, non antigentic, stuitable for cell attachment, proliferation and differentiation, flexible and elastic, three dimensional, osteoconductive and support the transport of nutrients and metabolic waste. Subsequently, studies reporting on the various advantages and disadvantages of using collagen based scaffolds in musculoskeletal and cartilage tissue engineering were identified. The purpose of this review was to provide a list of ideal characteristics of a scaffold as identified in the literature, identify different types of biological protein-based collagen scaffolds used in musculoskeletal and cartilage tissue engineering, assess how many of the criteria each scaffold type meets, and weigh different scaffolds against each other according to their relative properties and shortcomings. The rationale behind this approach is that the ideal scaffold material has not yet been identified. Hence, this review defines how many of the identified ideal characteristics are fulfilled by natural collagen-based scaffolds and address the shortcomings of its use as found in the literature.
[Back to top]


Chondrogenesis and developments in our understanding
Nigel Mabvuure, Sandip Hindocha, Daniel Jordan and Wasim S. Khan
[FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00120]

Conditions affecting cartilage through damage or age-related degeneration pose significant challenges to individual patients and their healthcare systems. The disease burden will rise in the future as life expectancy increases. This has resulted in vigorous efforts to develop novel therapies to meet current and future needs. Due to the limited regenerative capacity of cartilage, in vitro tissue engineering techniques have emerged as the favoured technique by which to develop replacements. Tissue engineering is mainly concerned with developing cartilage replacements in the form of chondrocyte suspensions and three-dimensional scaffolds seeded with chondrocytes. One major limiting factor in the development of clinically useful cartilage constructs is our understanding of the process by which cartilage is formed, chondrogenesis. For example, techniques of culturing chondrocytes in vitro have been used for decades, resulting in chondrocyte-like cells which produce an extracellular matrix of similar composition to native cartilage, but with inferior physical properties. It has now been realised that one aspect of chondrogenesis which had been ignored was the physical context in which cartilage exists in vivo. This has resulted in the development of bioreactor systems which aim to introduce various physical stresses to engineered cartilage in a controlled environment. This has resulted in some improvements in the quality of tissue engineered cartilage. This is but one example of how the knowledge of chondrogenesis has been translated into research practice. This paper aims to review what is currently known about the process of chondrogenesis and discusses how this knowledge can be applied to tissue engineering.

In the present study, a computational based pharmacophore and structural analysis were performed on a series of piperidinyl urea derivatives, a limited number of compounds which have variation in structure and activities that exhibit hERG blocking and H3 antagonistic activities. The conducted QSAR studies demonstrated that the developed models are statistically significant, which have been confirmed through validation. The Q2 values for the models developed with hERG blocking activity are >0.8 and with the H3 antagonistic activity are >0.6. The descriptors contributed in the models show that the distributed polar properties on the vdW surface of the molecules are important for the hERG blocking activity. The vsurf_ descriptors (surface area, volume and shape) such as vsurf_DD13 and vsurf_Wp4 correlate with the H3 antagonistic activity of these compounds. The distances between the pharmacophore sites were measured in order to confirm their significance to the activities. The results reveal that the acceptor (acc), donor (don), hydrophobic (hyd) and aromatic/hydrophobic (aro/hyd) pharmacophore properties are favorable contours sites for both the activities. Also, our study reveals that the distance between the polar contours (acc, don, etc) has to be small for better hERG blocking activity. The distances between the aro/hyd to the polar groups should be higher for better hERG blocking activity. However, the H3 antagonistic activity for these series depends upon hydrophobic property of the molecules, particularly the hyd and the hyd/aro contours of the molecules. Hence, these results reveal the requirements on the structural properties and the distances between the pharmacophore contour sites of the molecules responsible for their hERG and H3 antagonistic activities.
[Back to top]


Chondrogenic differentiation of adult MSCs
Griffin M, Hindocha S and Khan WS
[FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00121]

Chondrogenesis is a vital part of adult life, as cartilage is important not only for articulation of joints but also maintenance functions of the body. Chondrogenesis is a five way process of intricate events controlled by specific genes and cell-cell interactions which has been documented over recent years. This review highlights the current literature regarding the process of endochondral ossification and covers the different level of control at agent level. Due to the proliferative nature of chondrogenesis and using chondrocytes for self renewal and repair, current research involves finding ways in which to improve and replicate expansion of chondrocytes. The review summarises ways in which ex vitro expansion can be manipulated using growth factors, external sources and scaffolds.
[Back to top]


Expression of the Two Pore Domain Potassium Channel TREK-1 in Human Intervertebral Disc Cells
Pankaj Sharma, Stephen Hughes, Alicia El Haj and Nicola Maffulli
[FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00122]

Potassium channels play a major role in intracellular homeostasis and regulation of cell volume. Intervertebral disc cells respond to mechanical loading in a complex manner. Mechanical loading may play a role in disc degeneration. Lumbar intervertebral disc samples from 5 patients (average age: 47 years, range: 25-64 years) were used for this study, investigating cells from the nucleus pulposus and the annulus fibrosus duplicate samples to determine RNA expression and protein expression. Analysis of mRNA expression by RT-PCR demonstrated that TREK 1 was expressed by nucleus pulposus (n=5) and annulus fibrosus (n=5) cells. Currently, TREK-1 is the only potassium channel known to be activated by intracellular acidosis, and responds to mechanical and chemical stimuli. Whilst the precise role of potassium channels in cellular homeostasis remains to be determined, TREK-1 may be important to protect disc cells against ischaemic damage, and subsequent disc degeneration, and may also play a role in effecting mechanotransduction. Further research is required to fully elucidate the role of the TREK-1 ion channel in intervertebral disc cells.
[Back to top]


Stem Cells From Umbilical Cord And Placenta For Musculoskeletal Tissue Engineering
Umile Giuseppe Longo, Mattia Loppini, Alessandra Berton, Luca La Verde, Wasim S Khan and Vincenzo Denaro
[FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00123]

Mesenchymal stem cells isolated from amnion/amniotic fluid, umbilical cord blood, placental tissue, umbilical cord vein and the Wharton’s Jelly are promising candidates for musculoskeletal tissue engineering of bone and cartilage tissues. The extracorporeal nature of this source avoids the ethical concerns that plague the isolation of embryonic stem cells. Moreover, the harvesting does not require the invasive and discomfort extraction procedures as well as patient risks that attend adult stem cell isolation. Current preclinical studies support the application of these cell-based therapies for the regeneration of musculoskeletal tissues. We performed a review of the literature to focus on actual knowledge and the future perspectives of the stem cells deriving from umbilical cord and placenta for musculoskeletal tissue engineering.
[Back to top]


The Effects Of Ageing On Proliferation Potential, Differentiation Potential And Cell Surface Characterisation Of Human Mesenchymal Stem Cells
Fossett E, Khan WS, Pastides P and Adesida AB
[FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00124]

Mesenchymal stem cells (MSCs) have a great capacity for use in regenerative medicine and other clinical applications. However, one question creating curiosity of their use, is how they are affected by ageing. As we now live within an ageing population, the prevalence of age related disorders is increasing, so it is important to investigate how effectively MSCs from older patients can be expanded and differentiated in vitro before their use in autologous cell transplantation. This paper will look at how ageing effects proliferation potential, differentiation potential and cell surface characterisation of human mesenchymal stem cells.
[Back to top]


The Role Of Bioreactors In Cartilage Tissue Engineering
Nigel Mabvuure, Sandip Hindocha and Wasim S. Khan
[FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00125]

Cartilage tissue engineering is concerned with developing in vitro cartilage implants that closely match the properties of native cartilage, for eventual implantation to replace damaged cartilage. The three components to cartilage tissue engineering are cell source, such as in vitro expanded autologous chondrocytes or mesenchymal progenitor cells, a scaffold onto which the cells are seeded and a bioreactor which attempts to recreate the in vivo physicochemical conditions in which cartilage develops. Although much progress has been made towards the goal of developing clinically useful cartilage constructs, current constructs have inferior physicochemical properties than native cartilage. One of the reasons for this is the neglect of mechanical forces in cartilage culture. Bioreactors have been defined as devices in which biological or biochemical processes can be re-enacted under controlled conditions e.g. pH, temperature, nutrient supply, O2 tension and waste removal. The purpose of this review is to detail the role of bioreactors in the engineering of cartilage, including a discussion of bioreactor designs, current state of the art and future perspectives.
[Back to top]


Endothelial Progenitor Cells (Epcs) And Mesenchymal Stem Cells (Mscs) In Bone Healing
Nikolaos C Keramaris, Sarandos Kaptanis, Helen Lucy Moss, Mattia Loppini, Spyridon Pneumaticos and Nicola Maffulli
[FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00126]

Fracture healing is a complex physiological process. Local vascularity at the site of the fracture has been established as one of the most important factors influencing the healing process, and lack of vascularity has been implicated in atrophic non unions. Existing research has primarily involved utilising Mesenchymal Stem Cells (MSCs) to augment bone healing but there remains much scope to explore the role of stem cells in the vascularisation process. Endothelial Progenitor Cells (EPCs) and other Endothelial Cellular populations (ECs) could constitute a valid alternative to MSCs. This systematic review is examining the importance of co-implantation of MSCs and EPCs/ECs for bone healing.

A literature search was performed using the Cochrane Library, OVID Medline, OVID EMBASE and Google Scholar, searching for combinations of the terms ‘EPCs’, ‘Endothelial progenitor cells’, ‘angiogenesis’, ‘fracture’, ‘bone’ and ‘healing’. Finally 18 articles that fulfilled our criteria were included in this review.

ECs could be of value for the treatment of critical size bone defects as they are known to be capable of forming ectopic, vascularised bone. The co-implantation of ECs with MSCs is more intriguing when we take into account the vast array of complex reciprocal interactions between ECs and MSCs.
[Back to top]


Evaluation of biological protein-based collagen scaffolds in cartilage and musculoskeletal tissue engineering- A systematic Review of the Literature
Mafi P, Hindocha S, Mafi R and Khan WS
[FULL-TEXT INQUIRY] [BSP/CSCRT/E-Pub/00127]

The term tissue engineering is the technology that combines cells, engineering and biological/synthetic material in order to repair, replace or regenerate biological tissues such as bone, muscle, tendons and cartilage. The major human applications of tissue engineering are: skin, bone, cartilage, corneas, blood vessels, left mainstem bronchus and urinary structures. In this systematic review several criteria were identified as the most desirable characteristics of an ideal scaffold. These state that an ideal scaffolds needs to be biodegradable, possess mechanical strength, be highly porous, biocompatible, non-cytotoxic, non antigentic, stuitable for cell attachment, proliferation and differentiation, flexible and elastic, three dimensional, osteoconductive and support the transport of nutrients and metabolic waste. Subsequently, studies reporting on the various advantages and disadvantages of using collagen based scaffolds in musculoskeletal and cartilage tissue engineering were identified. The purpose of this review is to 1) provide a list of ideal characteristics of a scaffold as identified in the literature 2) identify different types of biological protein-based collagen scaffolds used in musculoskeletal and cartilage tissue engineering 3) assess how many of the criteria each scaffold type meets 4) weigh different scaffolds against each other according to their relative properties and shortcomings. The rationale behind this approach is that the ideal scaffold material has not yet been identified. Hence, this review will define how many of the identified ideal characteristics are fulfilled by natural collagen-based scaffolds and address the shortcomings of its use as found in the literature.
[Back to top]