The Unseen Power: Are We Discarding Critical Stem Cells in Bone Marrow Aspirate?
- kparmstrong1
- Jul 14, 2025
- 4 min read
Updated: Aug 6, 2025
In the dynamic world of spinal fusion surgery, Bone Marrow Aspirate (BMA) stands as a foundational therapy. For years, the prevailing paradigm has pushed us toward Bone Marrow Aspirate Concentrate (BMAC), assuming that “more concentrated” automatically means “more potent.”
But what if, in our drive for higher cell counts, we’re inadvertently discarding some of the most primitive — and potentially powerful — regenerative components?
This article challenges that assumption by exploring the possible role of Very Small Embryonic-Like Stem Cells (VSELs) and the idea that centrifugation may not be the ally we think it is.
We’ll also examine why, in the context of bone regeneration, a carefully harvested, minimally processed BMA might be just as effective — or even preferable — to concentrated marrow.
VSELs: The Tiny Giants You Might Be Missing
Beyond the well-known Mesenchymal Stem Cells (MSCs), bone marrow also contains a rare population of cells known as Very Small Embryonic-Like Stem Cells (VSELs).
Here’s why they’ve attracted attention:
Primitive Pluripotency: VSELs are extremely small (2–7 µm) with a high nucleus-to-cytoplasm ratio. They express key pluripotency markers such as Oct4, Nanog, and SSEA-1, suggesting broad differentiation potential.
Quiescent Sentinels: VSELs appear to remain dormant in adult tissues but can mobilize in response to injury, acting as “first responders” to initiate tissue repair.
Non-Tumorigenic: Despite their embryonic-like traits, VSELs have been reported as non-tumorigenic — a key advantage over embryonic stem cells.
However, it’s important to note: VSELs remain a controversial cell type. Some labs have struggled to isolate or confirm their existence, and their functional significance in humans remains under debate.
The Cost of Concentration: More Than Just Lost Cells
The very process designed to “optimize” BMA — centrifugation — may actually exclude or damage valuable components and introduce new risks:
Size & Density Mismatch: Because of their small size and unique density, VSELs may not pellet with RBCs nor float into the buffy coat during centrifugation. They may be discarded in the supernatant or remain in fractions not collected.
Mechanical Stress: High g-forces can potentially damage fragile cells or disrupt their quiescent epigenetic state — though this remains a hypothesis without definitive proof.
Time & Workflow Impact: Preparing BMAC adds extra time in the operating room — often 15–30 minutes.
Increased Exposure Risk: More handling and time outside the sterile field may increase the risk of contamination.
In short, the theoretical benefit of higher MSC counts must be weighed against these real-world costs — lost rare cells, longer procedure times, workflow complexity, and potential infection risk.
Bone Regeneration ≠ Intra-Articular Injection: The RBC Question
One rationale often cited for centrifugation is the removal of red blood cells (RBCs), which can cause irritation and inflammation — especially when injected into sensitive, enclosed spaces like joints.
But here’s the key distinction:
In bone regeneration, the local environment (marrow cavity, defect site) is already rich in RBCs and platelets.
There is no evidence that their presence impairs osteogenesis.
Thus, the benefit of RBC removal in bone applications is unproven — and may even be unnecessary.
Does BMAC Outperform BMA in Bone Healing?
Interestingly, while concentrated marrow increases MSC counts, there seems to be a lack of robust clinical evidence demonstrating BMAC improves bone healing outcomes compared to carefully harvested BMA.
Many studies confirm that adding BMA (or BMAC) to scaffolds improves outcomes versus scaffold alone.
But head-to-head trials of BMA vs. BMAC for spinal fusion, nonunion, or bone defects are virtually absent.
One study often cited, Muschler et al., JBJS Am. 2003;85(12):2127–37, showed that nucleated cell count correlates with fusion — but that was achieved with high-quality BMA and meticulous technique, not necessarily with BMAC.
This gap in evidence invites us to consider that concentrating marrow may not deliver the intended benefit — and could even diminish the regenerative potential by excluding rare, fragile cell populations or beneficial growth factors.
The Solution: Quality Harvest, Not Aggressive Processing
If over-processing is the problem, the solution lies in perfecting the harvest — collecting a high-quality, minimally contaminated whole bone marrow aspirate (WBM).
Here’s how:
Precision Aspiration Devices: New devices reduce peripheral blood contamination at the source, increasing the concentration of desired cells — including MSCs — without centrifugation.
Multi-Site, Small-Volume Aspirations: Harvesting 1–4 mL aliquots from multiple sites ensures high-quality marrow with minimal dilution.
Gentle, Controlled Suction: Excessive vacuum collapses sinusoids and draws in peripheral blood. Controlled aspiration preserves the marrow’s integrity.
By focusing on technique and thoughtful device design, we can collect marrow that already has an optimal mix of regenerative elements — with minimal manipulation and fewer risks.
A Paradigm Shift: Trusting Nature’s Full Spectrum
The drive for ever-higher MSC counts in BMAC is understandable — but may be shortsighted.
In the context of bone regeneration, we must ask:
Are we optimizing one component at the expense of others?
Is it better to preserve the marrow’s natural, synergistic milieu — including MSCs, VSELs (if functional), growth factors, and cytokines — rather than stripping it down to one fraction?
And is the extra time, complexity, and potential infection risk of centrifugation truly justified?
When considering the full picture — including the loss of rare regenerative cells, the questionable clinical benefit of MSC concentration, the added time, and the potential infection risk — it’s worth asking whether a simpler, more natural approach might serve our patients better.
Ready to Rethink What Makes a Bone Marrow Aspirate “Optimal”?
Let's hear your thoughts and experiences. Have you seen differences in spinal fusion outcomes between BMA and BMAC? What harvest techniques have you found most effective?
