Platelet-Rich Plasma Enhances the Clinical Outcomes of Microfracture Surgery in Older Patients

Osteoarthritis occurs when the cartilage that covers the opposing bones at a joint erodes away and the bare opposing bones smash into each other causing the bone to crack, fragment and chip. The result is extensive inflammation of the joint and further destruction of the bone, which prompts a knee replacement.

Because knee replacement surgeries are so painful and because they only last about two decades at the most, replacing the lost cartilage is a better option. One surgical treatment for osteoarthritis is microfracture surgery. Microfracture surgery involves the drilling of small holes in the tips of the bones of the joint to serve as conduits for stem cells in the bone to come to the surface and make cartilage.

Unfortunately, there are some problems with microfacture surgery, the most prominent of which is that it works better in younger patients than in older patients. Patients older than 40 years old show a precipitous drop in success after microfracture surgery. Thus, finding some way to increase the activity of cartilage production by endogenous stem cells would be a welcome finding for orthopedic surgeons.

Platelet-rich plasma (PRP) has been used to augment the cartilage-making activities of mesenchymal stem cells from bone marrow. Therefore, some surgeons from South Korea decided to try adding PRP to the knees of patients who had just had microfracture surgery. They examined 49 patients with early arthritis. All of these patients were subjected to arthroscopic microfracture surgery for a cartilage lesion that was less than four cubic centimeters in size. These patients were all between the ages of forty to fifty years old, which means that they were outside the age range for successful microfracture surgery.

These 49 patients were randomly divided into two groups. The first group was a control group of 25 patients that only had arthroscopic microfracture surgery. The second group consisted of 24 patients and they had arthroscopic microfracture surgery and injections of PRP into the knee. 10 patients from each group had follow-up arthroscopies four to six months after the procedure to determine the extent of cartilage restoration. Further evaluations were also done 2 years after the procedure.

The results? There were significant improvements in clinical results between preoperative evaluation and postoperative at 2 years post surgery in both groups (p = 0.017). However in the group that received PRP injections plus microfracture surgery the results were significantly better than those of the control group. These patients had better range of motion and less pain (p = 0.012). In the 2nd look arthroscopies, the cartilage of the patients that received PRP and microfracture surgery was harder and showed increased elasticity than the cartilage of patients that received only microfracture surgery.

The conclusion of these authors: “The PRP injection with arthroscopic microfracture would be improved the results in early osteoarthritic knee with cartilage lesion in 40-50 years old, and the indication of this technique could be extended to 50 years.” (Lee GW et al., “Is platelet-rich plasma able to enhance the results of arthroscopic microfracture in early osteoarthritis and cartilage lesion over 40 years of age? European Journal of Orthopedic Surgery. 2012 Jul 5., epub ahead of publication)  If PRP could improve the outcomes of microfracture surgery, then maybe such a technique could extend the groups of patients who are successfully served by this procedure.

While this is an exciting result, we must temper our excitement with the realization that this is a small study and MRIs were not used to measure cartilage thickness. Therefore, while this study is useful and frankly, ingenious, it has its limitations.

Genome of HeLa Cells Sequenced: It’s a Genetic Mess

HeLa cells are cultured cancer cells that have been used extensively in research. Historically, HeLa cells were used in the development of the polio vaccine and other types of research that led to two Nobel prizes. Over 60,000 publications have used HeLa cells in their research.

HeLa Cells

These cells received their name from the unfortunate young woman Henrietta Lacks, who died of cervical cancer and whose cancer cells were cultured to eventually produce the HeLa cell line, without her approval and without any compensation. The derivation of this cell line is the subject of a very fine book entitled “The Immortal Life of Henrietta Lacks” by Rebecca Skloot.

A recent paper has examined the genome of HeLa cells, and there were certainly some surprises. This paper was published in G3: Genes, Genomes, and Genetics, and this research project was led by Lars Steinmetz of the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany (Landry, J., et al. 2013. The genomic and transcriptomic landscape of a HeLa cell line. G3, doi: 10.1534/g3.113.005777). In this paper, the whole genome sequencing of HeLa cells showed that these cells have a haphazard combination of gene duplications and chromosomal rearrangements. Several chromosomes in the HeLa genome have been shattered and then randomly glued back together, and several genes exist in five or more copies apiece. All this has produced aberrant gene expression pathways that differ dramatically from normal human tissues. These findings could have a profound impact on how HeLa cells are used in the laboratory, according to the authors.

Even though HeLa cells grow well in the laboratory and are very hardy, scientists have known for some time that HeLa cells are not normal. However, according to Steinmetz, “nobody had sequenced the genome to figure out, at nucleotide resolution, where the rearrangements are in this genome. . . I was really struck by how abnormal these cells are.”

Given how heavily HeLa cells are used, the HeLa genome had never been sequenced. However, with the vast decrease in sequencing costs, Steinmetz and his EMBL team sequenced both DNA and RNA—1.1 billion DNA reads, each 101 base pairs in length, and 450 million RNA sequences—from the HeLa Kyoto cell line.

Their analysis of the HeLa genome showed that a dramatic phenomenon called chromosome shattering had occurred to a large degree in HeLa cells. Many chromosomes appear to have broken apart and then reassembled with countless chromosomal regions inverted or in the wrong order. Chromosome shattering is a recently described phenomenon that is associated with 2-3% of all cancers. In the case of HeLa cells, the chromosome shattering was probably original to Henrietta Lacks’ cervical tumor.

Other HeLa cell characteristics probably came about as the cells adapted over decades to life in the laboratory culture dishes. Steinmetz’s team used RNA analysis to show that HeLa gene expression differs dramatically from gene expression in normal human tissues. Cell cycle and DNA repair pathways are upregulated, which is expected for rapidly dividing cells. However, the genes associated with the immune system and environmental sensing are downregulated, which is expected for cells adapted to an isolated, nutrient-rich lab setting.

“We’re using these cells as our workhorse to study human biology,” said Steinmetz, “and if we have these genomic rearrangements, that’s clearly going to have some impact on the interpretation of gene function that we’re carrying out.”

For experiments in which genomic abnormalities don’t matter and scientists just need a lot of biological material quickly, HeLa cells are still suitable. But for genetic studies, the researcher must decide if HeLa cells are an appropriate model for addressing the research problem at hand. If that is the case, scientists can now use the HeLa genome rather than the Human Genome Project reference genome as a basis to better interpret experiments.