As a population ages, so do its knees. Americans undergo 700,000 knee-replacement operations annually – a number expected to quintuple within two decades.
Prosthetic implants, for the most part a godsend for those with knee problems, come with problems of their own. They can induce fractures in nearby bone. They can gradually loosen over time. Even in the absence of complications, they can wear out – their average lifetime is around 10 years – and a second surgery is technically tougher going than the first was.
In a fortunate development for the creaky-kneed among us, a study just published in Radiology and led by Stanford pediatric radiologist Heike Daldrup-Link, MD, PhD, promises to expedite clinical trials of a class of “adult” stem cells with great potential for knee repair.
These cells, known as mesenchymal stem cells (which I’ll call MSCs), ordinarily reside in bone marrow. Unlike embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), MSCs can’t differentiate into all the 200-plus tissues in the physiological rainbow that is our body. That’s good: A major concern about using ESCs or iPSCs for regenerative medicine is their capacity to form tissues wildly inappropriate for the job at hand or even to spawn tumors.
MSCs pretty much generate only bone, cartilage, muscle or fat, in response to cues from their immediate environment. Plus, they can be easily extracted from bone marrow of patients who are going to undergo the knee-repair procedure.
The trouble is, just shooting MSCs into a knee-injury site doesn’t automatically mean they’ll generate the wanted tissues, in the wanted amounts, right where they’re wanted. They might migrate away. They might die, refuse to engraft or fail to replicate and differentiate. They might develop into, say, scar tissue instead of cartilage or bone.
But how would you know? One way to see how newly transplanted MSCs are behaving requires labeling them, by loading them up with iron in the laboratory, between their extraction and their injection into the knee. This makes them visible via magnetic-resonance imaging (MRI), so they can be monitored afterwards.
But, as I wrote in my news release on the study:
Upon extraction, the delicate cells have to be given to lab personnel, incubated with contrast agents, spun in a centrifuge and washed and returned to the surgeons, who then transplant the cells into a patient.
Regulatory agencies and opinion leaders rightly look askance at the potential contamination that can be introduced when stem cells are manipulated in lab glassware. Besides, MSCs in a lab dish have scant appetite for iron particles.
Daldrup-Link’s team showed that – for whatever reason – the very MSCs that eschew iron in a dish munch it right up when they’re hanging out in the bone marrow. They gave rats an injected “snack” of ferumoxytol, an FDA-approved supplement composed of iron-oxide nanoparticles. When they later harvested MSCs from those rats’ bone marrow and infused them into other rats’ injured knees, they could track the the iron-stuffed MSCs for weeks afterward because they gave off a powerful MRI signal.
Stanford orthopedic surgeon Jason Dragoo, MD, plans to conduct a clinical trial this fall using the new MSC-labeling method. MSCs extracted from feroxytol-supplemented knee-damaged patients’ bone marrow will be delivered to those same patients in a single procedure, eliminating the delay and greatly reducing the contamination risk associated with lab-based labeling.
Previously: Nano-hitchhikers ride stem cells into heart, let researchers watch in real time and weeks later, FDA audit of Texas stem cell clinic revealed by Houston Chronicle and From college football player to team physician: A look at the career of Stanford’s Jason Dragoo
Photo by Jesse.Millan