MIMIT seminar series - bone regeneration

Regeneration of bone using off-the-shelf injectables: In-vivo homing of stem cells –
Professor Jons Hilborn

Bone conduction requires three main components; cells, matrix and growth factors. Bone is good at repairing itself, however severe injuries require therapy. Using human or animal tissue involves risk of virus transfer and ethical issues, but tissue engineering produces unique polymers with biological properties. The basic problem with foreign materials is the reaction of surrounding tissue i.e. formation of scar tissue/ poor vascularisation of the bone etc, therefore materials must be able to promote cell colonisation, nutrient diffusion and vascularisation.

There are two main approaches; in-vivo techniques that involve bone grafts, signalling molecules or cell/gene therapy or in vitro techniques i.e. culture system with scaffolds and a cell source. Traditionally stem cells are harvested, isolated, differentiated, seeded into a scaffold and then multiplied. Cells need a nutrient supply and can be stimulated to produce more protein and guide growth direction. Previous studies illustrate how bone can be fabricated from patient muscle, where CT scans demonstrate the ectopic bone formation. However poor vascularisation is still a problem, illustrating that formation of bone at the defect site is better than moving it.

Bone regeneration uses protein initiators called bone morphogenetic proteins (BMP’s); which regulate cartilage and bone differentiation. These proteins have specific cell surface receptors that bind to target receptors, initiating a cascade of events in the cell. The nucleic DNA is activated, gene products are produced and the cell transforms into osteoblasts and so forth. Clinical trials commonly use collagenous bone matrix, however other studies used heparin/chitosan injectables with BMP2 induced bone, on a titanium mesh covering the defect area. Side effects such as inflammation and fever indicate that a better carrier matrix is required. The ultimate goal is to produce a non animal, safe, bioresorbable composite of polymer and ECM with biochemical info to trigger tissue regeneration.

Prof Hilborn’s group used hyaluronan as a carrier for BMP2 which is advantageous as it is identical in all vertebrates, water soluble, biocompatible/biodegradable and functional groups can be modified. As a liquid, it is injected into the area to form a hydrogel (98-99% water) at pH 7.4/37c. The gel forms in less than 1 minute, by cross linkage in situ and hardens in 2-3 hours. Rapid gelation is vital in order to retain shape and prevent spreading after the subcutaneous injection. The gel degrades after staying in the muscle for 4 weeks and there is no indication of toxicity to surrounding cells. In vivo experiments were also carried out investigating the homing of stem cells, an osteoconductive nano-sized hydroxyapaptile filler was used as high density bone. The product was tested in mini-pigs, where a defect of 4cm x 2cm was created, no spontaneous healing occurred and then the gel was injected to form fully vascularised bone. There are proposed clinical trials for the use of this product in patients with cleft palates as they show more consistency compared to skull defects.

This hyaluronan based injectable has the necessary biocompatible properties and is much preferred than surgery. Pre clinical data is good and there is also the possibility of introducing ascorbic acid/ vitamin C in clinical trials to promote growth. It also has the potential to be used for other problems such as bone disease, formation of cartilage i.e. rheumatism and possibly repair in the nerves, muscle and brain.

Security at Manchester uni. Stopford building

The Stopford building, situated on Oxford road – home to the School of Medicine at The University of Manchester.

In addition to attending to my placement at Wythenshawe hospital, which I do like except it is so out of the way, it’s ridiculous. I mean I have to catch another train or bus to get there... anyway back to my main point, lol. As well as the hospital, the MIB (Manchester interdisciplinary biocentre – very nice place, kitted out with top tech stuff etc) and the John Rylands library, I also go to the Stopford building on a regular basis. My course administrator, my lectures and most of my professors/ lecturers are situated within the building and so I regularly need to see them.

Just one problem I have with the Stopford building, the over the top security system that they have in place. I mean I understand why you have to swipe your student card to get into the library or into restricted areas within the university, but why Stopford? My course administrator told me it was because they apparently store cadavers in the building for our anatomy classes etc and the uni feared that they might get stolen. Which brings me to the question, who in their right minds would steal a cadaver? Also if someone for some bizarre reason did want to steal one, I’m pretty sure somebody would notice as Stopford is quite a busy place and seeing someone drag a dead body along is not a common sight!

Ok so fine, we have the over the top security system... but it would be nice if it would work properly. Having to swipe your card through over and over again is time consuming, highly annoying, makes you late and puts you in a foul mood for the rest of the day. With the ever growing queue behind you and despite numerous swipe card attempts, the barrier still refuses to let you pass. Inevitably you let out an exasperated sigh/ wail/ squeak (whatever it is that you do when your stressed!), which makes the reception staff looks up from their newspapers. They either take pity on you and let you through (thank god!) OR remove you from the queue (Argh!), march you back to the reception desk, grill you on why your card isn’t working (ironically it works fine in the library!), provide some ID (Hello! you have a student card in your hand!) and then finally let you enter the building but extremely late for whatever lecture you were going to or person you were planning to meet.

I usually get away with just looking extremely harassed and so the staff just let me by with no problems, lol. However some of my friends get hassled so much and on a regular basis. I mean how many times do you have to prove that you are in fact a student? Seriously Stopford, sort it out!

Brain functions: Boys Vs Girls

I’m studying a lot about brain anatomy and function these days due to my MSc project and whilst searching for suitable brain images on Google, I came across a funny cartoon which got me thinking. About how brain functions in men and women can differ so much – more in terms of logic and thought processes as opposed to actual scientific differences.

It always makes me laugh how a simple situation, everyday common things, can evoke such different response from men and women. For example; I was recently walking with friends to some place or other at uni. Up ahead, someone had had a road accident, at rush hour which slowed traffic right down. After learning that it may have been a pedestrian walking out in front of a car – possible suicide attempt, the following responses of the group were:

Females – Oh my god! I hope he or she is ok. How sad that they tried to take their own life. Things must have been really bad, etc … u get the general gist of it.

Males – Idiot! Look at the traffic! Why did they choose rush hour to do it? Bloody attention seekers! Now we’re gonna be soo late. Argh.

Ok so maybe that’s not all men and women and I’m exaggerating slightly but my point was to illustrate the difference in responses over something so unexpected. Also the image in this post may be slightly unfair to the male population… but hey it made me laugh! :D

Also here's an article I found that I thought was an interesting read. For some bizarre reason, the link wouldn’t work so I've copied and pasted the content :)

ARTICLE:

5. Girls perform better at school
Girls are more likely to achieve higher grades than boys at GCSE and A-level. Among the suggested explanations for this disparity is the tendency for girls to mature earlier than boys, and therefore to be easier to teach. Adolescence for girls usually begins at age 12, whereas boys start to mature, on average, two years later at age 14. Boys are also more prone to hyperactivity (ADD) and dyslexia, which may affect their performance in school.

4. Women live longer
UK life expectancy figures have increased dramatically over the past century (men and women born in 1901 were only expected to reach the ages of 48 and 51.6 respectively). But the gap separating the sexes still remains prominent. Figures for 2008 show life expectancy for men to be 77.2 years, while the average woman can expect to live until she is 81.5. Men are also much more likely to commit suicide: three-quarters of the suicides in 2007 were committed by men. This has been blamed on social expectations for men not to verbalise their emotions.

3. Women make better citizens
In the UK, women make up less than 6 per cent of the total prison population (2005 statistics). It has been argued that the substantial gap between the number of male and female prisoners exists because judges show greater leniency towards female offenders in order to avoid separating mothers from children. Yet the nature of the crimes committed by women—the most common are shop-lifting, fraud and drug offences—differ from those committed by men, and suggest that female offenders pose less threat to public safety.

2. Women are safer drivers
Contrary to the popular stereotype, women are in fact safer drivers than men. In 2006 an overwhelming majority, 97 per cent, of motorists convicted of dangerous driving were male. While women are more likely to make low-level mistakes, such as stalling at a junction, men are prone to taking greater and more life-threatening risks, such as drink-driving or speeding.

1. Women are more cooperative
How the different genders interact with others has been the focal point of repeated studies, and most have shown that women are less competitive and focus more on cooperation than men. In one study held in 2007 participants played "The Prisoner's Dilemma," a game where contestants must choose between the desire to be selfish and the need for compromise. (The premise of the game is that you and your partner in crime are arrested for stealing a painting, which is spattered with blood. You are held in separate cells and do not know what your partner will say. If you both stay silent and cooperate, you will both serve short jail sentences for theft. If you inform and accuse your partner of murder, you will get away scot-free. If, however, you and your partner inform on each other, you will both serve long jail-sentences.) Women consistently chose to cooperate with each other, thereby achieving higher payoffs than men.

Even in situations of stress, women appear to react in a more cooperative manner. Brain scans of 16 men and 16 women put in situations of moderate tension showed that blood flow in women's brains increased in the limbic area, the part of the brain associated with a nurturing and friendly response. Men's blood flow, meanwhile, increased in the area of the brain responsible for the "flight and fight" reaction.

Year 2

It’s amazing how quickly time flies by and yet those memories that I have, still seem so fresh in my mind. It’s as if the whole thing only just happened yesterday.

I recently saw another family member leave us this year, uncle Mirza Sahib. He passed away near the end of Ramzan and his 40 day khatum fell close to Aisha’s 2 year anniversary. I still can’t believe that he’s actually gone, I mean it was just so sudden. They had been round to deliver Shazia baji’s wedding invites and we were all sat laughing and joking, teasing Bilal, all the usual stuff, Bilal running off to fetch his draughts set (his favourite game that he loves playing with all my uncles). Basically a good evening with family. The next thing I know is that I was woken up at 1am, to be informed that uncle had passed away an hour after he left our house. I don’t think it really sunk in until I got up for Sehri the next morning and tears started to flow as I remembered the events from last night.

The day progressed through all the various traditions and customs but I still had this feeling of disbelief. Even after seeing all those people at the house gathered together to say their goodbyes, even after seeing his face with my own eyes; where a smile was ever present. Yet I still couldn't quite grasp the situation at hand. But I think seeing uncle’s grave near Aishi’s is when it really hit home; the fact that I wouldn’t actually see him ever again and that really got to me. My relationship with uncle actually changed significantly over the time I had known him. I spent my childhood a bit afraid him as he seemed like the strict disciplinarian type, but how wrong was I? :) As the years went by, I got to know him better and I actually found it easier to have a conversation with him than with my own father at times. I guess in a way he was like another father figure, just like Tyagee and Saeed Mamoo are to me; which has been very comforting to me especially over these last few years.

It became a regular thing to have uncle pop over in the evenings after work. Whilst having his usual cup of coffee, he’d have a quick game of draughts with Bilal and talk to me at the same time. With uncle Mirza Sahib, I was able to switch between joking around to discussing issues such as politics, education, science, everyday life... basically you name it and we could sit down and have a discussion on it for hours. I also improved my draughts game as well and quoting uncle I was a worthy opponent, but still needed some more practice apparently, lol. I think I actually beat him once (just the once!) and even then I think he let me win, something I'm still not sure about.

I know my father will miss him a lot as well. I know for a fact that uncle was my dad’s favourite “go-to” guy whether it be personal issues or otherwise. Uncle was one of the first people that dad stayed with when he moved over to the UK and everything started from there really. He may not have been the most religious or the most out spoken but he was a good man and well respected. He will be dearly missed by all and may his soul enter Janaah (Ameen).

MIMIT seminar series - curing baldness

Curing Baldness –

Professor Ralf Paus

Hair loss/unwanted growth reflects problems in the hair follicle cycling due to problems i.e. malnutrition. The hair cycle is controlled by chemical signals and has three distinct phases; anagen (production), catagen (apoptosis) and telogen (rest). It was previously thought that hair follicles were only formed during fetal development, which is not true. Hair transplantations are used to fill in thinned scalp hair using micrografts and products that alter hair growth by conservation/preservation are available. The aim of hair research is to find a cure which is safe, inexpensive and minimally invasive.

Stem cells (SC’s) are responsible for producing hair follicles (HF’s) and the two SC populations are found in the bulge area and dermal papilla of the hair shaft. There are two main theories for hair restoration: cloning and regeneration/reactivation. General approach to cloning is to remove stem cells, multiply in suitable media and reinject new stem cells back to stimulate/produce new follicles. The SC populations can also be mixed together in culture to produce primitive follicle structures which are injected back into the scalp. Neogenesis (a fetal event) has been successful in mouse studies but not human whereas adult neogenesis is possible but problematic. Cell processing outside the body may produce undesirable results. Clinical problems such as painful cysts, granuloma and even skin cancer and cosmetic problems can occur; therefore hair needs to be strong, full pigmentation, voluminous and of correct orientation. On the other hand, current FDA approved drugs such as minoxidil and finasteride, prove follicular regeneration is possible. Even when hair follicles aren’t visible, stem cells are still present i.e. alopecia. Injecting these steroids into bald areas initiated re-growth, suggesting a reversible event; as follicles can be switched on/off.

An alternative approach would be to find biochemical messengers that control the on/off process of follicles. Other studies used mice experiments to investigate follicle behaviour where wounds were created in mouse skin, certain genes were turned on/off and during healing processes it was found that new hairs were formed. Prof Paus’ team suggest that regeneration of dormant follicles is a better method than travelling in a new direction like cloning and are currently working on TGFB/BMP signals during hair follicle development. Animal studies have been completed and the next stage is to start human clinical trials.

Prof Paus suggests that as well as looking regeneration of hair follicles, adult epithelial and mysenchymal hair follicle stem cells could be used for in vitro production of skin to cover defects via transplantation. Using potentially useful markers of the mouse system, immunohistochemistry, immunofluorescence, microarrays and proteomic analyses are used to select epithelial and mysenchymal stem cells containing hair follicle compartments. The discovery of epithelial stem cells (eSC’s) near the bulge region of the hair follicle have lead to the identification of a number of SC populations that are crucial to wound healing; providing an ideal model system for stem cell biology and identification of reliable stem cell markers.

To conclude; it is easier to conserve rather than surgically restore hair and hair cures are more likely to be found via methods of regeneration i.e. identifying biological chemical mediators for reactivation, as opposed to cloning of follicles. Stem cells have the potential to become anything and the hair follicle itself is a cell farm that is ideal for research in this rapidly advancing field.

MIMIT seminar series - nerve repair

Regenerating nerves after injury: A novel polymer conduit for peripheral nerve repair –
Professor Sandra Downes

The human nervous system is made of the peripheral and the central nervous system. Damage to the peripheral nerve can lead to loss of sensation and function and affects about 1 in 1000 people. Nerve repair is an ongoing area of research and damage to the peripheral nerve can be repaired and regenerated unlike the central nerves. Current methods involve nerve autography but this process is ineffective with a number of problems such as loss of function at the donor site, sub optimal recovery and grafts are often the wrong diameter. A better method is required and tissue engineering allows the combination of cell based therapies with biomaterials.

Previous work has shown that nerve regeneration can be enhanced by using artificial nerve conduits to transplant Schwann cells; which are essential for repair as they multiply rapidly, secret growth factors and clear debris. Clinical use of Schwann cells is limited however as sufficient numbers are hard to produce in a short time and so methods are being sought to solve this problem. Alternative methods would be to use adult multi-potent stem cells that can be differentiated into functional Schwann cells for therapeutic use. There are other ongoing projects investigating nerve repair and results from different materials used will hopefully help to produce a scaffold with the best properties. The aim of this study was to create a polymer conduit that protects the nerve during healing and as the nerve repairs itself, the conduit degrades overtime.

The biocompatibility and biodegradability of the conduit are essential points and the group produced a novel material composition along with a new seal of the conduit. The material has a unique molecular structure that allows the conduit to degrade from the surface inwards, thus avoiding an acidic burst of polymers such as PCA. The conduit is minimally invasive, non toxic, sterilized, low cost, highly efficient and has a controllable microenvironment. It allows the ability to control surfaces, grow Schwann cells and nerve cells together and attract the appropriate growth factors. Early preclinical work in rats has shown no scarring, correct muscle attachment and a lack of inflammation. The nerve regeneration was illustrated by staining nerves with antibodies to show the area of cell repair. This early work has allowed FDA approval and further physiology tests, such as the grip test can be run on animals to see of the functionality of the nerves has been restored.

With FDA approval already in place, the conduits can be patented and have tremendous commercial potential. The route to market has been identified as producing a cluster of patents that can be licensed out to appropriate manufacturers. Future aims are to develop the material to improve directional growth and patent these new surfaces. Work on topographical nerve direction has already begun using processes such as in vitro testing, photolithography and wet etching. There is also the possibility of making the conduits electro-conductive in order to help directional growth and kick start nerve activity. Other ideas are to use the conduit to repair nerves in the central nervous system and tackling problems such as optical nerve blindness in newborns. To conclude, the conduit is a suitable solution to a current clinical problem and has many opportunities for future development and applications.

Aah Facebook, you do make me laugh

This blog post made me literally laugh out loud. Facebook strikes again.

http://maniacmuslim.com/2006/11/27/facebook-profile-ruins-marriage-proposal/

If only the girl in article had a dislike button, that way she could accurately detail when and where he went wrong. Lol.

On second thoughts, why limit it to just this case? I think Facebook needs to introduce a ’dislike’ for everyone just the same as the ‘like’ button. Some status updates are just plain odd.

Selling myself...

lol. No not that kind...

I meant in terms of filling in applications for jobs or further uni courses can be so stressful. Am I the only one who finds it hard to sell themselves on a single side of A4? Also when I write something down I’m concerned as to how the reader will perceive it... will they think I am arrogant or that I don’t know how to sell myself effectively? I suppose it’s one of those things that will never end and I will have to repeatedly have to do it throughout the rest of my life. Well I can only hope it gets easier over time! Urgh... right then. Rant over. Back I go to filling in endless forms!!!

Caller ID

Wonder who's calling - time to run or be direct?

I know, I should probably get caller ID as it would avoid scenes like this;

*Phone rings, dad answers*
Dad: “Hello”
Caller: “Hello Mr Ahmed. How are you?”
Dad: “Yes fine thank you. Sorry who is this?”
Caller: “Mr Ahmed, we’ve heard that someone in your household has had a car accident recently.”
Dad: *Puts the phone down and looks at me* “Anything you need to tell me? Forgotten perhaps?”
Me: “Err, not that I can remember. Why?”
Dad: “Someone said you had a car accident”
Me: “Who?”
Dad: “The woman on the phone”
Me: *Being sarcastic* “Yes, because cold callers are never wrong and know EVERYTHING”
Dad: ”Sooo… is that a NO then?”

Or this
*Phone rings, mum answers*
Mum: “Hello”
Caller: “Hello Mrs Ahmed. How are you?”
Mum: “I’m fine, thank you”
Caller: “Mrs Ahmed did you know that *insert number* (hundreds/ thousands/ millions) of (people/ cats/ dogs/ any living thing) dying every (second/minute/week/hour/month/year)?
Mum: “Oh really? That is terrible”
Caller: “Yes I know Mrs Ahmed, which is why…”

And so the caller follows this up with a bombardment of more facts and figures etc which keeps my poor mum on the phone for at least a good 20 to 30 minutes. Quite often they manage to persuade my mum into doing whatever they want her to do (bless her) whilst my dad just puts the phone down on them (he just doesn’t have the time, lol).

I can usually detect when a caller is selling me something so I usually make up some excuse (bad I know!) or quietly cut them all off whilst they’re running through their spiel. Recently however I have been tricked on more than once occasion! People will ring and upon answering the phone they will usually respond with “Assalamu Alaikum” the islamic equivalent of hello. It tricks me into thinking it might be someone my parents may know etc and so I will continue the conversation until I’m pretty sure it’s not someone I know. However by this point it’s harder to cut the call off as I’ve been talking to them for a while (sneaky eh?) and so I will continue talking to them and wait for them to come up for air/ take a pause so that I can interrupt and tell them politely to go away.

It’s not all bad though and you do get funny sales people as well, sometimes. Tom from O2 and Hassan from Sky TV – I’m looking at you guys! Making idle chit chat or telling me how lovely my voice sounds over the phone will not make me increase the value of my mobile phone package or sign up to new TV packages. Yet they still don’t get and will ring again every couple of months. And it’s the same guys every time – I think they are being trained to break my spirit! Bring on the caller ID!

Getting back into it...

Hmm I haven't blogged in a while so I thought I'd get back into blogging by writing up some of my preferred seminar reviews from the MIMIT series at university. Oh yea, did I mention I was back at uni again? lol

Rather randomly, I’ve suddenly found prank phone calls funny again – no that’s not an invitation for everyone to start ringing from withheld numbers! I think it’s something to do with being very bored and a uni student. Sixth form – not funny, uni – funny, working – not so funny, uni – funny. I can see a pattern forming, can you? Urgh... I need to get out more, lol!

Divisions between Facebook and Twitter

Like I said before, I do like using new technology and services as opposed to some friends who are just a tiny bit hesitant... but I’m working on them ;) So far I’ve got those friends to join Facebook and I think they like using it. Therefore I thought the next thing I should get them signed up to is Twitter and explained what it was all about. Except I don’t think they liked this idea as much, but I’m not sure why. I’m on both Facebook and Twitter and essentially they are both ‘social networking’ sites, but I feel like there is a difference between the two services.

Twitter is all about keeping in touch with people but on a much larger scale and it may not feel as personal as Facebook as some people have many thousands of followers. It allows you to update everyone on what you’re up to and in return you keep up to date on everyone else you follow. It’s a bit like a newsfeed but it has more of a community feel as you get to pick and choose who you do and don’t follow. However with twitter, it’s become more of a family thing for me as most of my followers and the people that I’m following are close family members. For me it’s nice to be able to see at a glance what most of my family are up to, especially if I’ve been busy and haven’t had the chance to meet up with them properly.

On the other hand, I feel that Facebook is more of a personal service as the people that you add to your profile are usually real family and friends, people that you know and have probably met face to face. It’s usually a close group of people, though there are exceptions as some people have like over a 1000 friends added to their accounts. The point is that that you may not meet these people very often, but being able to write on each other’s walls, tagging friends in various photos and using apps like superpoke, makes it a lot more fun than exchanging normal emails to keep in touch. It’s the ‘in’ thing at the moment and if you like is the acceptable face of the emailing as it’s cool at this moment in time.

So there, that’s my opinion on the topic. Does anyone else feel like that or is it just me?

Does what happen in Facebook stay in Facebook?

http://www.albumoftheday.com/facebook/  

In one word. No

A little obvious but I’d be careful of what you put up on Facebook, because once it’s out there, it is out of your control. An obvious statement but if just take a moment to scroll through your friends list you always be able to pinpoint the people that will regret posting that status or tagging that picture... and you never know who might find it later on.