Hip Replacements- Made Real by Surgery and Stem Cells

When my friend's mum fell and broke her femur about 3 years ago, she had to have almost complete bed rest for six months and physiotherapy and rehabilitation for close to three months after that. With a metal screw pin in her thigh bone and a cast around her leg, it was probably the most uncomfortable and frustrating experience for someone who was living a very active lifestyle (tai chi, walking in parks, overseas travel etc.) prior the incident. She has since recovered from the injury but mentions feeling occasional discomfort and tightness in her thigh.

Most people live their early and active life not expecting any bone surgery (unless it is cosmetic) and most fractures tend to happen in osteoporosing elders over sixty. However, hip fractures are far worse than femur fractures the incidence of hip fractues increase with age, doubling for each decade after fifty. Most people who fracture their hips in old age have a poor quality of life and often get depressed and there are estimates that one in four people who fracture their hips completely heal while 20% of those who fracture their hips do not survive the year of their injury.

Given these considerations, it is therefore not surprising that doctors and bio-engineers are often looking at ways to make prostheses more natural and better accepted by the body. In the reported work that is currently being done at University College London (UCL), the doctors are keen on ensuring that people who require a second hip replacement (about 25% undergo a second surgery) will have a better outcome rather than suffer a crumbling joint with a high probability of trauma (apart from a nasty scar) and protracted recovery period involved.


Professor Gordon Blunn's team at UCL's Institute of Orthopaedics collaborates with Dr. John Skinner's group from the Royal National Orthopaedic Hospital in Stanmore, are conducting a trial with a GBP 130,000 (approx. RM 897, 150) grant from the UK Stem Cell Foundation and the Medical Research Council for a preliminary trial -to boost patient's bone growth by 75%- which will lead to a larger trial of 80 patients next year.

The current method of surgery requires bone chips to be packed into damaged hip joints to rebuild, followed by the insertion of the artificial replacement hip. What the research team will do is to improve the quality of the implants by infusing the bone chips with the patient's own stem cells, which they believe might act as a better cement and cause less inflammation.

The cells would be obtained from each individual patient's bone marrow which is extracted from the patient's hip bone under anaesthesia, isolated and grown in the laboratory and used to seed the bone chips.

The cell culture is estimated to cost approximately GBP 2,000 (approx. RM 14,000) and this probably excludes the cost of the surgery and any ancillary medical care.

The Chief Executive of the Medical Research Council, Sir Leszek Borysiewicz summarized this work most clearly when he said:

"The idea is to use autologous stem cells [taken from the patient themselves] to accelerate healing and outcome."



QUESTIONS AND THOUGHTS

I thought that there were a few interesting points to take from the concept and the trial.


APPLICATION IN OTHER BONES

Firstly, that marrow stem cells were being infused into the interior of artificial bone as seeding for normal bone structures to form.
-This is not the first time that stem cells have been used to seed bone growth and to kickstart the healing process. It would be interesting to see this method applied in other bones too.


AGE IS NOT AN ISSUE

Secondly, that the autologous stem cells harvested from the patient (usually 60-80 years of age) would still be clearly functional for this purpose, demonstrating that stem cells obtained from an older individual is still useful.


ENOUGH FROM THE SOURCE?

Thirdly and curiously, I wondered where the stem cells would be harvested from in these patients. One has to bear in mind that marrow stem cells are usually collected by puncturing the hip bone. Hence, if these patients are already having their second hip replacement, there can't be much left after all the inflammation and debris to harvest. This might provide the reason why stem cell isolation and growth in the lab becomes an important factor.

The number of stem cells infused needs to be optimal in order for the healing to accelerate and outpace the degenerating tissue, by signalling the required repair factors. I would be most interested to know what that optimal number might be in these cases.



*An renown South African orthopaedic surgeon that I spoke to recently told me that at a recent medical convention, he asked the audience (all doctors) who would undergo and prefer a prosthesis vis-a-vis a natural joint. The answer? Nobody raised their hands for a prosthesis.

Verdict: 100% of doctors themselves would opt for a natural method of joint salvage than have a prosthesis inserted.


If you'd like to watch a hip replacement procedure, here's one I found which gives you an idea of what happens but is censored so that there is none of the gore...

Viacell ABANDONS Cord Blood Stem Cell Expansion Program

IS IT ENOUGH?

Whilst many cord blood banks rather unscrupulously hype up the possibilities of stem cell expansion (in order to get clients to store whatever they have and believe in their technology), I've always asked the StemLife team to take a very careful view of the science and the practical realities*.

[As a side note, here in Malaysia cord blood banks claiming to compete with us - operate on the cheap using non-FDA approved storage systems- promote the usage of vials as a storage medium on the pretext that cells can be selectively taken one vial at a time for future expansion. Read on to see why this is a disingenuous marketing ploy...]


THE CHALLENGES OF EXPANSION

The reason why StemLife has taken a cautious approach towards the expansion technology are three fold.

Firstly, in order to expand stem cells, you'll need enough cells -the more the better- in the first place. As a crude analogy, you'll need enough lactobacilli to make yoghurt (too little and it will take too long, allowing other bacteria to destroy the process).

Secondly, sterile technique is absolutely critical; when you're growing the cells, you have to make sure that it contains only the cells that you're growing and nothing else. This requires not only human precision, expensive facilities and sterile reagents, but most importantly, the money to maintain everything in exactly this pristine sterile condition (many, many zeros in any currency).

Thirdly, knowledge of cellular morphology and function is also very important. No one I know would like to risk having cells injected into the heart forming liver or kidney tissue instead. This means identifying the cells and providing the assurance that the cells are indeed stem cells and nothing else.

Hence, any organization, private or public has to be prepared to have deep pockets and a lot of patience when venturing into this technology.


HOW DEEP ARE YOUR POCKETS?

I've been following Viacell's (VIAC) progress in this area for some time, not only because they were one of the first stem cell companies to announce their sincere interest and demonstrate their financial committment in this area, but also because I was kindly shown around their big and beautiful facilities two years ago in Boston.

It is unfortunate therefore to see this press release by Viacell on their decision to terminate the cord blood stem cell expansion project CB001 despite its apparent reported success but on the grounds that the process and product was unaffordable and commercially inviable due to other alternatives.

"What's the alternative?" I hear you ask. The reason why Viacell made the tough commercial decision to cut their losses was that the preferred methodology by transplanters in the US is a dual cord stem cell transplant (using 2 cord blood stem cell units instead of just 1). The results of the expanded product were as good as and in some ways slightly better in the initial trial, but I suspect that the cost did not justify only small improved outcomes. I would say that it was a wise commercial decision by Viacell, and an acknowledgement that what scientists dream and love to do, is not always feasible for clinical practice.

I learned this a long time ago when I was still in research, that what looks good on paper does not necessarily transform into a money spinner despite the winning ideas and long hours of toil.


A GOOD CEO KNOWS WHEN TO QUIT

By cutting the budget for this research and focusing on service improvements, Viacell expects to finally achieve profitability in 2008 for the first time since their listing a few years ago (this is probably also true of many of the other cord blood banks which have committed much of their funding to very costly research, sacrificing their bottom line).


"Given these results and the shift in the treatment paradigm in transplant medicine from single cord to two cord transplants, ViaCell has made the decision not to advance CB001 in future clinical trials. As a result of the reduced clinical and development costs related to CB001, along with anticipated continued growth in its operating business, ViaCell expects to become cash flow positive in the first half of 2008."


Now, Viacell intend to focus on cord blood stem cells for cardiac applications, which I think is probably more interesting and may pose less life-threatening consequences for patients.


"We are committed to continuing to grow our operating business, advancing ViaCyte(SM) through a pivotal clinical trial, which, if successfully developed, will leverage our sales and marketing infrastructure, and working to advance our cord blood-derived cardiac program," said Mr. Beer. "We are already generating cash flow within our ViaCord business and we anticipate continued growth in 2007. As a result, given our reduction in clinical and development costs related to CB001, we expect ViaCord's contributions to the overall operation will allow us to turn cash flow positive in the first half of 2008."


So if you are specifically told by any stem cell company that stem cell expansion technology is available today, they aren't lying, but don't forget to ASK them whether:

1. Your unit baby's cord blood unit has sufficient stem cells to be expanded,

2. Who's offering the service (full due diligence here) and how successful the treatments outcomes have been and what assurances they provide otherwise;

3. And, specifically at what cost.


STEMLIFE BELIEVES IN CHOICES

The way I read the cord blood stem cell tea leaves, if you banked a unit of stem cells and it is not enough, seek other matching units to combine with your own or consider joining StemLife's adult stem cell banking program.

We believe in continually providing affordable and accessible options to our clients... and making stem cell banking a more than once in a lifetime opportunity. :)



*We do not turn away clients who express their wish to proceed but provide them with a cautious advisory to indicate if the stem cell counts are below what we would normally expect. StemLife also provides a full refund for those clients who decide not to proceed to store, and we usually ask them to let us know when they'll be having the next baby (success second time round).

StemLife has a joint research project with the National University of Singapore at very initial stages which differs from Viacell's approach, you can read more about it here.