Skeletal tissue engineering using mesenchymal or embryonic stem cells: clinical and experimental data.

INTRODUCTION: Mesenchymal stem cells (MSCs) can be obtained from a wide variety of tissues for bone tissue engineering such as bone marrow, adipose, birth-associated, peripheral blood, periosteum, dental and muscle. MSCs from human fetal bone marrow and embryonic stem cells (ESCs) are also promising cell sources. AREAS COVERED: In vitro, in vivo and clinical evidence was collected using MEDLINE® (1950 to January 2014), EMBASE (1980 to January 2014) and Google Scholar (1980 to January 2014) databases. EXPERT OPINION: Enhanced results have been found when combining bone marrow-derived mesenchymal stem cells (BMMSCs) with recently developed scaffolds such as glass ceramics and starch-based polymeric scaffolds. Preclinical studies investigating adipose tissue-derived stem cells and umbilical cord tissue-derived stem cells suggest that they are likely to become promising alternatives. Stem cells derived from periosteum and dental tissues such as the periodontal ligament have an osteogenic potential similar to BMMSCs. Stem cells from human fetal bone marrow have demonstrated superior proliferation and osteogenic differentiation than perinatal and postnatal tissues. Despite ethical concerns and potential for teratoma formation, developments have also been made for the use of ESCs in terms of culture and ideal scaffold.

West Yorkshire Mentor Scheme: teaching and development.

BACKGROUND: The West Yorkshire Mentoring Scheme (WYMS) was created to provide a framework for clinical supervision, teaching and support by foundation year (FY) doctors for final-year medical students. Although established literature highlights the benefits of near-peer teaching, the accompanying mentoring role has little been explored. This study explored the impact of the WYMS for FY doctors and final-year medical students. METHOD: FY1 mentors were individually paired with fifth-year medical students from the University of Leeds. The scheme aims to provide support, teaching and skills development for both mentors and mentees, as students rotate through clinical placements and assistantships. At the end of each academic year, FY1s and medical students are invited to complete an online questionnaire to highlight their experiences. These data were used to explore the impact of the scheme, and thematic analysis was employed to determine the results. RESULTS: Forty-nine medical students and 122 FY1s responded: 98 per cent of mentors and 100 per cent of mentees would recommend the scheme to their peers. Thematic analysis demonstrated that the scheme proved useful in skills development, teaching supervision and increasing preparedness for work. DISCUSSION: WYMS is well received, beneficial and an excellent, local adjunct to clinical placements. It is of significant value to final-year students and their FY mentors, assisting in the development of student assistantships and clinical placement design. For FY doctors, it is a rewarding scheme that develops essential attributes of time management, communication and leadership for mentors and for the junior doctors who organise the scheme.

Stem cells combined with bone graft substitutes in skeletal tissue engineering.

INTRODUCTION: Bone grafting is used to repair large bone defects and autograft is recognised as producing the best clinical outcome, which is partly due to its cellular component. When autograft is unavailable, allograft and bone graft substitutes can be used; however, they rely on the host bed to provide cellular osteogenic activity. AREAS COVERED: Bone graft substitutes have the potential to benefit from the addition of stem cells aimed at enhancing the rate and quality of defect repair. Mesenchymal stem cells (MSCs) can be isolated from bone marrow or periosteum and culture expanded. Other sources of primary cells include muscle, adipose tissue, human umbilical cord and the pluripotent embryonic stem cells (ESCs). EXPERT OPINION: MSCs isolated from bone marrow have been the best characterised approach for osteogenic differentiation. Their use with synthetic scaffolds such as hydroxyapatite and tricalcium phosphate has produced promising clinical results. MSCs derived from adipose tissue, muscle or human umbilical cord cells combined with various scaffolds are an attractive option. Further in vivo and clinical investigation of their potential is required. Pluripotent ESCs have a theoretical advantage over MSCs; however, purification, cell-specific differentiation, effective delivery vehicles-scaffolds and teratogenesis control are still under in vitro and in vivo evaluation.

Growth hormone: does it have a therapeutic role in fracture healing?

BACKGROUND: The role of growth hormone (GH) in augmenting fracture healing has been postulated for over half a century. GH has been shown to play a role in bone metabolism and this can be mediated directly or indirectly through IGF-I. OBJECTIVES: The use of GH was evaluated as a possible therapeutic agent in augmenting fracture healing. METHOD: A literature search was undertaken on GH and its effect on bone fracture healing primarily using MEDLINE/OVID (1950 to January 2009). Key words and phrases including 'growth hormone', 'insulin like growth factor', 'insulin like growth factor binding protein', 'insulin like growth factor receptor', 'fracture repair', 'bone healing', 'bone fracture', 'bone metabolism', 'osteoblast' and 'osteoclast' were used in different combinations. Manual searches of the bibliography of key papers were also undertaken. RESULTS: Current evidence suggests a positive role of GH on fracture healing as demonstrated by in vitro studies on osteoblasts, osteoclasts and the crosstalk between the two. Animal studies have demonstrated a number of factors influencing the effect of GH in vivo such as dose, timing and method of administration. Application of this knowledge in humans is limited but clearly demonstrates a positive effect on fracture healing. Concern has been raised in the past regarding the safety profile of the pharmacological use of GH when used in critically ill patients. CONCLUSION: The optimal dose and method of administration is still to be determined, and the safety profile of this novel use of GH needs to be investigated prior to establishing its widespread use as a fracture-healing agent.

Statins: under investigation for increasing bone mineral density and augmenting fracture healing.

BACKGROUND: Statins are 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors and have been shown to possess anti-lipidaemic properties effective in lowering cholesterol. Recent evidence has suggested beneficial pleiotropic effects, including that of fracture healing, alongside its widely accepted ability to reduce the incidence of cardiovascular disease. OBJECTIVES: A comprehensive review of the recent literature on the effect of statins on bone mineral density and fracture healing. METHODS: Medline/Ovid and EMBASE search and manual search of bibliography of key papers, on the effects of statins on bone metabolism including in vitro and in vivo studies, as well as clinical trials on the effects of statins on bone mineral density and fracture risk. RESULTS/CONCLUSIONS: There is robust in vitro and in vivo evidence to suggest the anabolic effects of statins on bone metabolism. Although evidence in patients with osteoporosis is conflicting, several studies have shown that the use of statins is associated with increases in bone mass density and reduction in fracture risk. Conflicting studies identified may be due to different routes of administration, types of statins employed and low doses used. Taken together, there is strong evidence to suggest that statins have beneficial effects on fracture healing that would support further clinical trials investigating such properties.