Health of Bone Marrow Depots

One theme of the last few posts on Dr. Philippe Hernigou’s pioneering use of BMC to treat soft and bony tissue pathologies has been the need to boost the bone marrow cellularity and/or its vitality. What? You haven’t caught on that the real objective of treating orthopedic pathologies is to make sure the adjacent bone marrow depot is fully stocked with MSCs? At least that is the impression I have formed from reading Dr. Hernigou’s clinical studies, and availing myself of the opportunity to speak with him on a number of occasions on the importance of having healthy bone marrow depots.

It goes without saying that if your bone marrow isn’t functioning, you either are being treated with ablative therapy (while waiting for a cord blood or bone marrow transplant) or you are dead. I offer the latter option, since there are some who make remarks along the lines that as you age you lose all of the MSCs in your bone marrow—but not in your adipose tissue. This is, of course, rubbish. If you have no MSCs in your bone marrow you are dead, since otherwise the various bone marrow depots would not be functional and you would not be producing neutrophils, platelets, RBCs and WBCs to live to fight (infectious agents) another day. MSCs are thought to maintain the stroma of the marrow so that the HSCs can produce the various components found in your bloodstream. No MSCs, no supportive stromal environment, no mature blood components.

Dr. Hernigou has published a couple of papers addressing the dynamics of MSC levels in pathologic tissue of viable patients. For example, in a paper entitled “Decrease in the mesenchymal stem-cell pool of the proximal femur in corticosteroid-induced osteonecrosis,” he and his co-workers measured the CFU-F levels in the osteonecrotic site in the femoral head of patients with corticosteroid-induced (CS) osteonecrosis, in patients with sickle-cell disease-associated (SCD) osteonecrosis and in control patients. The number of CFU-F in the osteonecrotic site itself was zero for both the CS and SCD patients, which indicates that “dead” sites have no MSCs. But just outside the necrotic zone, the CS patients had an average of just 1.88 MSCs per million bone marrow cells, while the SCD patients had 31 MSCs per million bone marrow cells. The control population had 34 MSCs per million bone marrow cells in their non-necrotic femoral heads. Obviously, there is a big difference between the CS patients and either the SCD or control patients. There was no statistical difference between the frequency of MSCs in SCD and control patients.

While the mechanism for corticosteroid-induced osteonecrosis wasn’t well established, Dr. Hernigou and co-workers speculated that the reduction observed in tissue adjacent to the osteonecrotic lesions in the femoral heads of SC patients might result from the influence of the corticosteroid on the fatty deposits found in normal bone marrow depots after the age of about 25. The point being that a pathologic condition existed and a decrease in MSC content was observed. Why the SCD patients, who also had osteonecrosis of the femoral head, didn’t show a corresponding drop also isn’t known. However, Dr. Hernigou has observed that SCD patients have higher levels of MSCs in general in their bone marrow, so perhaps there is a mechanism to keep MSCs elevated in those patients.

On the other hand (shoulder?), Dr. Hernigou has published a study of the factors that influence the level of MSCs present in the greater tuberosity in patients undergoing rotator cuff repair versus control patients. These patients have suffered a physical damage to their shoulder, in contrast to the patients in the first paper who either had Sickle-Cell disease or corticosteroid-induced osteonecrosis. The paper entitled “Reduced levels of mesenchymal stem cells at the tendon-bone interface tuberosity in patients with symptomatic rotator cuff tear” is sort of a companion article to the Hernigou clinical study I reviewed recently. In that clinical study, he indicated that 87% of the BMC-treated patients had an intact tendon at 10-year follow-up compared with just 44% of the control group who had the same surgical repair, but no BMC treatment.

While the rotator cuff repair clinical study was limited to patients with a full-thickness tear of the supraspinatus tendon only, the study on MSC levels in the greater tuberosity tracked MSC levels in patients undergoing surgical repair of rotator cuff tendon tears of any complexity. There was a control group of patients who were undergoing shoulder surgery, but not for tendon repair. Both sets of patients agreed to have their bone marrow depot in the greater tuberosity biopsied prior to their surgery.

As Hernigou and co-workers reported, patients with more complex tears, a longer lag time between index event and surgical repair, the degree of fatty infiltration or age of the patient all showed statistically significant reductions in the greater tuberosity bone marrow depot of the repaired shoulder compared to MSC levels in control patients. The worst conditions were associated with more than a 70% reduction in the MSC content, meaning that for complex tears, higher degrees of fatty infiltration and 1-2 year lag times prior to repair, a patient could suffer a serious depletion of MSCs in the bone marrow depot next to the repair site.

In part, these observations support my original comment about needing a healthy and vital bone marrow depot in order to have a healthy joint, with well-functioning tendons and cartilage surfaces. Because, when you have a dysfunctional joint due to a pathology the MSCs in nearby tissues are depleted. This is one reason why Dr. Hernigou always goes to the iliac crest for his bone marrow aspiration—pathologic sites are associated with depleted MSC content.

By the way, Dr. Hernigou will be giving a couple of lectures at the upcoming ASIPP conference the third week of April in Las Vegas, NV. One of his talks will be on the utility of BMC treatments in the elderly. As an added bonus, I will be at the meeting staffing the Greyledge booth in the technical exhibit area, so drop on by and say hello. My boss, Dr. David Karli, also will be at ASIPP to give a talk as well. So, now you have three reasons to attend the conference.

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