Is Obsession with MSC Count Sabotaging Spinal Fusions?

While traditional autografts and bone marrow concentrate (BMC) have both shown promise, there is an argument to be made that allowing marrow to clot—preserving its full array of cells, platelets, and growth factors—may optimize the regenerative response.

Why Does Bone Marrow Matter in Spinal Fusion?

A robust spinal fusion requires forming stable, vascularized bone across vertebral segments. Autologous iliac crest bone graft has been considered the “gold standard,” but issues with donor‐site morbidity and limited graft volume drive the search for less invasive, biologically rich alternatives. That’s where bone marrow aspirate (BMA) comes in—delivering mesenchymal stem cells (MSCs), hematopoietic progenitors, platelets, and growth factors directly to the fusion site.

Over the years, bone marrow concentrate (BMC) has taken center stage because it is believed to increase the MSC density, making it a prime driver of new bone formation. However, an argument can be made that focusing only on MSCs risks losing the synergy provided by the whole marrow.

For clarity, any argument for using bone marrow in any form is predicated on using aspiration techniques to draw quality bone marrow. 

The Case for Clotted Bone Marrow Aspirate

Clotted BMA involves letting the aspirated bone marrow form a natural fibrin clot, encapsulating not just MSCs but also immune cells, platelets, and myriad growth factors (e.g., VEGF, TGF‐β, FGF2). The theory is this clot, which can be formed with synthetic bone grafts, may:

• Retain growth factors and MSCs at the implantation site (reducing washout)

• Enable higher cell viability and colony‐forming potential

• Promote enhanced osteogenic and chondrogenic gene expression

• Eliminates extra steps (like centrifugation) that may remove beneficial elements

These theory echos what has been seen historically believed in fracture‐healing circles: the initial clot or hematoma results in the spark for bone repair—stabilizing growth factors, recruiting osteoprogenitors, and initiating angiogenesis.

Whole vs. Concentrated: The Emerging Consensus

We should be debating in regenerative orthopedics whether it’s more advantageous to concentrate marrow, thereby boosting MSC counts, or to keep the whole marrow intact. Historically, the “more MSCs, the better” logic drove the popularity of BMC, but is that right?  Isn’t bone healing multicellular and multifactorial? Don’t platelets release essential growth factors like PDGF and TGF‐β during the clotting process and these signals help recruit and stimulate osteoprogenitor cells (including MSCs)? Likewise, can’t beneficial immunomodulatory cells (like certain monocytes or macrophages) be filtered out if marrow is over‐processed?

Biological Rationale: The Clot as “Scaffold + Cells + Signals”

What may well set clotted BMA apart is the formation of a natural fibrin matrix:

• Scaffold: Fibrin strands form a 3D mesh that locks in place and provides a provisional structure for progenitor cells.

• Cells: Not just MSCs, but also endothelial progenitors, monocytes, and other synergistic cell populations remain within the clot.

• Signals: Platelet degranulation and fibrin’s partial degradation release a variety of growth factors over time, fueling the local microenvironment crucial for bone formation and vascular in‐growth

Practical Implications for Spine Surgeons

1. Simplified Technique: Clotted BMA forms spontaneously in 15–30 minutes, requiring minimal specialized equipment or repeated aspiration steps (once again, proper aspiration techniques still need to be adhered to for quality bone marrow).

2. Reduced Donor‐Site Morbidity: Surgeons can harvest marrow from the vertebral body (during pedicle screw preparation) instead of the iliac crest.

3. Stable Placement: The clot “sticks” at the defect or fusion bed, rather than diffusing away like a liquid aspirate.

4. Holistic Biologic Boost: By not discarding RBCs, plasma, or platelets, the synergy of the entire marrow environment is retained.

Future Directions

• Clinical Trials: As always, randomized trials comparing clotted BMA to conventional BMC or autograft in multi‐level fusion scenarios would help confirm best practices.

• Optimized Protocols: Studies are needed on how best to prepare, handle, and combine clotted BMA with other biomaterials (e.g., ceramics, collagen sponges).

• Patient Subgroups: Populations with poor bone quality (e.g., osteoporosis) or significant comorbidities may benefit disproportionately from a more robust synergy of all the marrow’s cellular constituents.

Concluding Thoughts

Bone marrow’s regenerative capacity may well extend beyond MSCs alone. Clotted BMA capitalizes on the entire regenerative orchestra by preserving platelets, red blood cells, immune cells, and essential cytokines in a stable fibrin scaffold. For spinal fusion surgeons striving for faster, stronger, and more predictable fusions—clotted bone marrow aspirate may well be a big leap forward.