Percutaneous autologous bone marrow concentrate for knee osteoarthritis: patient-reported outcomes and progenitor cell content

Abstract

Purpose: Knee osteoarthritis (OA) is a common, progressively debilitating joint disease, and the intra-articular injection of autologous bone marrow concentrate (BMC) may offer a minimally invasive method of harnessing the body's own connective tissue progenitor cells to counteract accompanying degenerative effects of the disease. However, the extent to which the progenitor cell content of BMC influences treatment outcomes is unclear. We sought to determine whether patient-reported outcome measures associated with BMC treatment for knee OA are related to the concentration of progenitor cells provided.

Methods: In the present study, 65 patients (72 knees) underwent treatment for knee OA with autologous BMC and self-reported their outcomes for up to one year using follow-up questionnaires tracking function, pain, and percent improvement. A small fraction of each patient's BMC sample was reserved for quantification with a haematological analyzer and cryopreserved for subsequent analysis of potential connective tissue progenitor cells using a colony-forming unit fibroblast (CFU-F) assay.

Results: Patients reported significant increases in function and overall percent improvement in addition to decreases in pain relative to baseline levels following treatment with autologous BMC that persisted through 12 months. Patients reporting improved outcomes (46 of 72 knees) received BMC injections having higher CFU-F concentrations than non-responding patients (21.1×10³ ± 12.4×10³ vs 14.3×10³ ± 7.0 x10³ CFU-F per mL). A progenitor cell concentration of 18×10³ CFU-F per mL of BMC was found to best differentiate responders from non-responders.

Conclusion: This study provides supportive evidence for using autologous BMC in the minimally invasive treatment of knee OA and suggests that increased progenitor cell content leads to improved treatment outcomes.

Trial registration: ClinicalTrials.gov Identifier: NCT03011398, 1/7/17.

Keywords: Bone marrow concentrate (BMC); Colony-forming unit fibroblast (CFU-F); Connective tissue progenitor cells; Knee osteoarthritis (OA).

Fig. 1

Consort flow diagram

Fig. 2

Patient-reported outcomes following treatment with autologous BMC for knee OA. Violin plots of reported A pain (NPS), B function (LEFS), and C percent improvement (SANE) at 1-, 3-, 6-, and 12-month follow-ups from patients receiving intra-articular (black) or intra-articular and intraosseous (blue) injections. Lines represent mean values. One symbol P < 0.05, two symbols P < 0.01, three symbols P < 0.001 versus baseline (*) and 1-month follow-up (^#)

Fig. 3

Responders to autologous BMC therapy for knee OA tend to have more progenitor cells in their injectates than non-responders. The A CFU-F concentration, B CFU-F frequency, C nucleated cell concentration, D volume, E age, and F BMI of patients and their BMC when separated based on outcome (non-responder = N, responder = R). Images of multi-well CFU-F assay plates representative of patients having (enlarged symbols in A–F) G lower and H higher CFU-F concentrations. Horizontal lines represent mean values. * P < 0.05, ** P < 0.01

Fig. 4

Patients having higher concentrations of CFU-F within their autologous BMC therapies generally report better outcomes. Scatter plots of A change in function (ΔLEFS) and B percent improvement (SANE) at 6-month (black symbols) and 12-month (white symbols) follow-ups versus CFU-F concentration. The C ΔLEFS and D SANE for those above and below the CFU-F concentration value of 18×10³ CFU-F per mL of BMC. Lines represent mean values. * P < 0.05, ** P < 0.01, *** P < 0.001 versus ΔLEFS = 9 and SANE = 40%