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

BMC via IV Infusion

In the previous post, I reviewed the risk-based approach the FDA is taking in dealing with the free-for-all that currently exists in the world of regenerative medical therapies, like BMC and PRP. Actually, PRP and BMC don’t seem to raise red flags with the FDA, unlike amniotic fluid, cord blood-based products, fat-derived SVF in orthopedic indications, fuzz balls (i.e., mechanically-fractured fat), etc. One important element of their risk-based approach announced last November in the Agency’s Guidance on Minimal Manipulation and Homologous Use (MM/HU) concerns the route of administration, with the FDA really frowning on treatments provided via IV or intraocular routes, for example.

While the FDA made it clear they wouldn’t tolerate riskier routes of administration, like IV, they made the statement in the context of the injected material being an HCT/P. But what if the material isn’t an HCT/P. In particular, what if the material is an autologous bone marrow-derived therapy?

The reason I ask is that the FDA made statements about the use of bone marrow in the MM/HU Guidance:

Bone marrow is a source of hematopoietic stem/progenitor cells.  [foot note 17, p. 13]

And:

Example 16-1: Relevant biological characteristics of hematopoietic stem/progenitor cells generally include the ability to repopulate the bone marrow by self-renewal and by differentiating along myeloid and lymphoid cell lines.

Example 19-1: Sources of hematopoietic stem/progenitor cells (HPCs) include cord blood, peripheral blood, and bone marrow… The basic functions of HPCs include forming and replenishing the lymphohematopoietic system.

It is clear from these excerpts that the FDA considers bone marrow to be a source of HPCs, which can be used to repopulate bone marrow depots, especially in patients who have had their bone marrow ablated by chemo/irradiative methods.

From a review of the literature on repopulating an ablated patient’s bone marrow with HPCs from donor-derived bone marrow, the only route I could find for the repopulation was via IV infusion of the donated bone marrow (see here for an early review). Autologous bone marrow also has been used for recapitulating bone marrow following an ablation, via an IV infusion.

Thus, the FDA endorses the use of bone marrow for recapitulating a patient’s ablated bone marrow via an IV infusion. Consequently, as the FDA acknowledges, this is one example of a homologous use for bone marrow, both donor-derived and autologous, which is administered as an IV therapy. The obvious implication is that IV infusion of bone marrow isn’t viewed as being especially risky, since it has to have been performed hundreds of thousands, if not millions, of times over the past 30 years or so.

Now the question is, since the FDA considers that one basic function of bone marrow is to replenish depleted bone marrow depots, which is achieved via IV infusion, is there any evidence that would support this indication for use in the regenerative medical world?

As it happens, I believe there is evidence of the need for replenishing bone marrow in patients who are experiencing musculoskeletal deficiencies and pathologies. Dr. Hernigou, at the same MedRebels conference where Dr. Buford presented, made a number of interesting observations about the level of MSCs found in bone marrow, including the depletion of MSCs in the tibial plateau of patients suffering from osteoarthritis of the knee. MSCs are one kind of stem/progenitor cell found in bone marrow.

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

More importantly, he has published a paper on the level of MSCs (as measured by a CFU-F assay he has been using in his laboratory for more than 30 years) found in the greater tuberosity in patients undergoing surgical repair of the shoulder due to tendon tears, compared to individuals undergoing shoulder surgery without rotator cuff injury. His focus in the study wasn’t on showing efficacy in using BMC as an augmentative treatment that improves the durability of surgically-repaired rotator cuffs (see Hernigou, et al. 2014 for that clinical study), but on the numbers of CFU-Fs found in the greater tuberosities of the study subjects. The study involved sampling the bone marrow depots of 125 patients presenting with rotator cuff injury and 75 patients without rotator cuff injury (controls), and determining the CFU-F content in the greater tuberosities of the two cohorts.

Dr. Hernigou and co-workers reported that patients with rotator cuff injuries showed a statistically significant reduction in the number of CFU-F cells present in the bone marrow depot of their greater tuberosity of the pathologic shoulder compared to control patients. In fact, the extent of the reduction in CFU-F levels for patients with rotator cuff pathology was statistically significantly correlated with the lag time between occurrence of the pathology and surgical repair, the number of tendons involved, the degree of fatty infiltration and the extent of tendon tear. This publication supports the idea that bone marrow depots lose their progenitor cells in response to joint pathology and tissue degradation.

I have been laying the groundwork for how an IV infusion of bone marrow is viewed as a homologous use for replenishing depleted bone marrow depots. I will consider the implications of an IV infusion with BMC to treat musculoskeletal conditions in the next post.

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