Bone marrow and cell therapies are the orthobiologics most likely to be described to a patient as a stem cell treatment, and the gap between that description and what is actually injected is the central issue for the sport and exercise medicine (SEM) clinician. The group includes bone marrow aspirate concentrate (BMAC), adipose-derived preparations, and culture-expanded cell therapies, and they differ from each other in how the tissue is obtained, how much it is processed, what the final preparation contains and how it is regulated. This page covers how each preparation is produced, what is realistically in it, and what the evidence supports. The regulatory framework that determines which of these becomes an advanced therapy medicinal product (ATMP) is set out in the related orthobiologics material, and the two pages should be read together.
How are these preparations produced?
Bone marrow aspirate concentrate is produced by aspirating marrow, usually from the posterior iliac crest of the pelvis, and centrifuging it to concentrate the mononuclear cell fraction. The harvest itself is a procedure in its own right: it is performed under local anaesthetic with or without sedation, using a bone-marrow aspiration trocar, and it can be painful despite local anaesthesia, with donor-site soreness afterwards that patients frequently underestimate. Taking multiple small-volume aliquots while repositioning the trocar at different depths or locations may reduce dilution with peripheral blood. There is no single standard harvesting protocol: needle design, aspiration volume, processing system and final cellular composition all vary substantially. The resulting product is heterogeneous and system-dependent, commonly containing variable proportions of blood cells, platelets and a very small population of cells with mesenchymal stromal or progenitor properties, which is precisely why calling it a stem cell treatment is misleading. Harvest-specific risks include donor-site pain, bleeding or haematoma, infection, complications of anaesthesia or sedation, and rare neurovascular or bone injury.
Marrow is aspirated from the posterior iliac crest and centrifuged. Fat is harvested by small-volume liposuction and then either mechanically processed or enzymatically digested, which are two distinct routes.
Adipose-derived preparations start with fat harvested by small-volume liposuction, usually from the abdominal wall or the flank, and then follow one of two routes that should never be conflated. Mechanical processing, by washing, emulsifying and filtering, produces preparations such as microfragmented adipose tissue, in which the fat is broken down but the tissue architecture is largely retained. Enzymatic digestion, typically with collagenase, breaks the tissue down further and can isolate a stromal vascular fraction, which is a cell suspension rather than a tissue. The distinction matters clinically because these are distinct products, and it matters legally because regulatory classification is product-specific and the degree of manipulation is one of the determining criteria. Culture-expanded cell therapies are a separate category again: cells are isolated and grown in a laboratory over weeks before implantation, which produces far greater cell numbers and takes the preparation out of the single-procedure model. Culture-expanded cells intended for therapeutic use will generally meet advanced therapy medicinal product criteria, although formal classification is product-specific.
What does the evidence show?
The evidence base for these preparations is less mature and generally of lower certainty than the platelet-rich plasma literature, which is itself heterogeneous rather than uniformly negative, and it is important not to let the sophistication of the technology imply a corresponding strength of evidence. Most of the literature on bone marrow aspirate concentrate consists of case series and small cohort studies in knee osteoarthritis and in tendon and cartilage lesions, frequently without a placebo comparator and often with industry involvement. Where randomised comparisons exist they are typically against another injectable rather than against a sham procedure, and direct comparisons against platelet-rich plasma have generally not established a clear clinically important advantage for the more invasive and more expensive option, although that evidence is limited and does not prove equivalence. Adipose preparations are in a similar position, with the added complication that mechanically processed and enzymatically derived products are frequently pooled in reviews despite being different interventions. Culture-expanded cell therapy has the smallest clinical evidence base in this setting, and its use in the UK sits within the medicines framework rather than in routine practice.
Marrow concentrate is heterogeneous and system-dependent, with cells having mesenchymal stromal or progenitor properties forming only a very small and variable proportion, which is why the label stem cell treatment is misleading.
Several specific problems recur and are worth being able to name. The preparations are poorly characterised, so the injected product varies between providers and between patients, and studies rarely report cell counts or composition in a way that allows comparison. The marrow harvest is itself painful and is often accompanied by a period of relative rest and rehabilitation, so an uncontrolled improvement cannot be attributed to the cells. Outcome measures and follow-up vary widely. Commercial interests are prominent, and the treatments are expensive and almost always privately funded. The reasonable clinical position is that these preparations should not be routine care. Where a patient asks about them the discussion should cover what the preparation actually contains, the cost, the procedural burden of the harvest and the weakness of the evidence. Where they are offered, use formal governance, transparent consent and outcome audit, with participation in registered research preferred. Where the regulatory position of a specific product is uncertain, the medicines regulator's innovation office can be asked for a classification view, and tissues and cells used as starting material also carry tissue authority requirements.
Exam Tips
•Bone marrow aspirate concentrate (BMAC) is produced by aspirating marrow, usually from the posterior iliac crest, and centrifuging it to concentrate the mononuclear fraction.
•Taking multiple small-volume aliquots while repositioning the trocar at different depths or locations may reduce dilution with peripheral blood; there is no single standard harvesting protocol.
•The product is heterogeneous and system-dependent, containing only a very small and variable proportion of cells with mesenchymal stromal or progenitor properties, so calling it a stem cell treatment is misleading.
•Adipose preparations follow two distinct routes: mechanical processing produces preparations such as microfragmented adipose tissue, while enzymatic digestion can isolate a stromal vascular fraction.
•Culture-expanded cell therapies involve laboratory growth over weeks and will generally meet the criteria for an advanced therapy medicinal product (ATMP) when intended for therapeutic use.
•The evidence base is less mature and of lower certainty than the platelet-rich plasma literature, and limited direct comparisons have not established a clear advantage for marrow concentrate, which is not the same as proving equivalence.