Considerations On the Regulatory Status of IV Administration of BMC: A Useful Shot in the Arm? Part Three

BMC via IV Therapy

Over the previous couple of posts, I have been reviewing the love/hate relationship the FDA seems to have with therapy provided by an IV route. They issued a blanket determination in the MM/HU Guidance that IV therapies of HCT/Ps would be considered risky and therefore physicians offering IV therapies of HCT/Ps would be more rapidly scrutinized for potential mis-deeds. On the other hand, the FDA has acknowledged that bone marrow can be used to treat ablated patients in order to restore their bone marrow functionality when delivered by an IV route.

Related Posts: Considerations On the Regulatory Status of IV Administration of BMC: A Useful Shot in the Arm? Part One and Part Two

Let’s recap the situation with replenishing bone marrow depots adjacent to a patient’s degenerating joint:

  • The FDA acknowledges that one of the basic functions of bone marrow in a donor is to maintain a healthy bone marrow depot, capable of supporting production of hematopoietic stem cells in the depot.
  • The standard method for replenishing bone marrow in a patient with a deficient bone marrow is to introduce bone marrow with IV therapy.
  • The infused bone marrow cells migrate into the bone marrow depots in a patient receiving the bone marrow, where they can recapitulate a bone marrow depot in an ablated patient, thereby restoring all of the functions of the depot.
  • Hernigou has shown that bone marrow depots adjacent to pathologic or osteoarthritic joints have lost stem/progenitor cells usually found in a healthy bone marrow.
  • Hernigou has reported that injecting BMC intra-osseously into the long bones of elderly patients with severely osteoarthritic knees can improve the health of the bone marrow depots near the joint by increasing the number of progenitor cells present in the depot, resulting in reduced pain and an improved quality of life.
  • The cells in BMC, a concentrated bone marrow aspirate, introduced via IV infusion in patients should migrate to depleted bone marrow depots, just as occurs with cells in donor-derived bone marrow that is infused into ablated patients.

Thus, there are some tantalizing parallels between the well-established, and FDA sanctioned, use of bone marrow infused via the IV route into patients who were ablated and patients who have suffered musculoskeletal damage to joints, with the concomitant loss of progenitor cells in the adjacent bone marrow depots as reported by Dr. Hernigou (see Part Two of this series). Obviously, since IV infusion of bone marrow is an accepted therapy for treating seriously depleted bone marrow depots (i.e., chemo/irradiative ablated patients), why couldn’t a patient with an orthopedic injury, like joint osteoarthritis, benefit from receiving IV therapy of their own bone marrow concentrate?

One argument the FDA might advance is that the mechanism of migration of IV infused bone marrow-derived cells isn’t well established in an orthopedic indication for use. But I would argue that it would be no less mysterious than how donor-derived bone marrow cells end up in a patient’s ablated bone marrow depots. In theory, it is the same process—cells homing most likely in response to signals sent out from the tissue cells adjacent to the depleted bone marrow depots telling the circulating cells to come on down!

The FDA also might try to say that the risk to an ablated patient undergoing an IV infusion of bone marrow cells is far less than the risk of dying from the cancerous pathology. They have a point. Except the adverse events usually associated with IV therapy of cells (cord blood or bone marrow) usually occur as a result of a reaction against the donor-derived graft material, or from the preservative used during the freeze down of the donated unit. In the case of an autologous BMC infusion, the material comes from the patient’s iliac crest, so there are no issues of tissue incompatibility, and since the BMC is processed at point-of-care, there is no need for cryostorage and no preservatives.

I also would point out that while a patient with mild to moderate osteoarthritis might not be addicted to opioids in the near term, there is a serious risk of patients becoming more reliant on painkillers of the addictive kind as their disease progresses. Wouldn’t it be better to allow for IV infusion of a patient’s BMC during the early stages of OA joint disease, in order potentially to delay disease progression and the need to use ever more addicting painkillers?

The FDA might argue that there is no evidence that a basic function of BMC in the donor is to mitigate pain, so use of BMC to treat knee pain in the patient isn’t homologous use. Okay. However, as I have indicated in the last post, Dr. Hernigou and co-workers have shown that pathologic joints result in a depletion of progenitor cells in the adjacent bone marrow depots, which would benefit from getting a boost of stem/progenitor cells. Dr. Hernigou has reported that delivery of BMC via the intra-osseous route has resulted in reduction in pain and improved functionality of elderly patients with severe osteoarthritis in the knee. Intra-osseous delivery of BMC definitely boosts the level of progenitor cells in the bone marrow depots, which has the added benefit of improving the patient’s quality of life and reducing pain. What’s not to like?

Some of you might argue that there is no medical need to do an IV therapy with BMC, since there is no algorithm for treating musculoskeletal conditions in this manner. So, get cracking! I would argue that subclinical pathology in the joints and surrounding tissues might very well be treated with BMC taken from the iliac crest and infused by the IV route. That insurance companies wait until a patient is racked with pain and requires a total knee arthroplasty just means that the insurance companies don’t care about the welfare of patients, whereas physicians do care about their patients’ quality of life.

Of course, there will be those who point to studies that show cells accumulating in the lungs when infused via the IV route. I wouldn’t expect the cells to make a beeline for the depleted bone marrow depots in just a single tour through the body. But just because the cells end up in lung tissue, doesn’t mean that they die in that location. I suspect there is a lot of movement of progenitor cells through the lymphatic system as they relocate to pathologic sites. Migration via the frequently overlooked lymphatic system could explain why the progenitor cells typically aren’t detected in the circulation—they quit flying around the body by coming to rest in the lungs or other organs. Consequently, I suspect that since MSCs don’t die off, after catching their breath in the lung, so to speak, they move off to other locations in the body, potentially including pathology-depleted bone marrow depots.

Bear in mind that I have a PhD and am not suggesting that a physician should treat patients complaining of knee pain due to osteoarthritis with IV therapy of their own bone marrow concentrate or to do this on a prophylactic basis when pathology might be subclinical. On the other hand, if bone marrow-derived cells infused via IV find their way to the bone marrow depots of ablated patients, it most likely will work in patients suffering from a less drastic depletion of bone marrow cellularity induced by aging and osteoarthritis. Will this provide a boost in a patient’s depleted bone marrow? Hard to say. In any event, with the precedent of using bone marrow to treat ablated patients via IV therapy, it seems to me to be a topic worth investigating as a clinical treatment for patients with less severe depletion of their bone marrow depots.

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