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Cited by 6Mesenchymal stem cell researchPeriodontal Regeneration and TreatmentsOsteoarthritis Treatment and Mechanisms

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Posterior iliac crest vs. proximal tibia: distinct sources of anti-inflammatory and regenerative cells with comparable 6-month clinical outcomes in treatment of osteoarthritis

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Mormone, E., Savastano, L., Rossi, G., Maruccia, F., Di Maggio, G., Sinisi, N. P., Sandri, M., Copetti, M., De Santis, E., Guerra, V., Biancofiore, G., Cisternino, C., Caradonna, E., Graziano, P., Gorgoglione, F. L.·2024·Journal of Translational Medicine
DOI 10.1186/s12967-024-05924-yPMC PMC11616267
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Abstract

BACKGROUND: Human bone marrow is a source of mesenchymal stem cells (MSCs), other progenitor cells, and factors with anti-inflammatory and regenerative capacity. Though the fraction of MSCs out of the nucleated cells is very small, bone marrow aspirate (BMA) for osteoarthritis (OA) has noteworthy effects. BMA is usually collected from the posterior or anterior iliac crest, and rarely from the proximal tibia. We investigated the clinically beneficial concentration of ex vivo MSCs, derived from BM harvested from the posterior iliac crest and proximal tibia by Marrow Cellution™ Aspiration System, and their phenotypic differences, in comparison to autologous Platelet-Rich Plasma (PRP) treatment prepared with a manual, closed system. METHODS: A single-center, parallel, randomized controlled study was designed to investigate the efficacy of BMA from the posterior iliac crest compared to BMA from the proximal tibia, against a control group treated with PRP, in knee OA. Thirty patients with knee OA grade I-IV, according to Kellgren-Lawrence (KL), were distributed into each group. Visual Analog Scale (VAS) and Western Ontario & McMaster Universities Arthritis Index (WOMAC) score were used for clinical outcome evaluation. RESULTS: Data from an intermediate analysis of 6-months follow-up, involving 15 patients in each arm, showed that the posterior iliac crest was significantly more densely populated with mononuclear cells, than the proximal tibia (p = 0.005). Flow cytometric analysis on ex vivo BMA showed a significantly greater number of MSCs in the BM-derived from the posterior iliac crest when compared with the proximal tibia (p < 0.001), together with a significantly higher number of platelets (PLTs) (p < 0.001). Surprisingly, despite these differences in cells number, the improvement in early pain and function scores, after each treatment, were statistically significant within each of the three arms. BM from the proximal tibia showed the highest ΔWOMAC, while BM from the posterior iliac crest showed the highest ΔVAS; however, these differences were not statistically significant across the three arms (p > 0.05). A better outcome, in terms of ΔVAS, was observed in patients classified as KL I-II, when treated with BMA from crest (p < 0.001) and PRP (p = 0.004). Moreover, the effect of BMA treatment on ΔVAS depends on MSCs % only in the Tibia Arm (r = -0.59, p = 0.021), where we also found a correlation between ΔWOMAC and monocytes (r = 0.75, p = 0.016). CONCLUSION: The results indicate that the iliac crest yields a higher concentration of MSCs compared to the proximal tibia, however both BM, independently of the MSCs concentration, show a beneficial clinical outcome in the treatment of knee OA. Furthermore, BMA is not superior to PRP treatment.

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  • Mormone et al. showed that BMAC obtained from the iliac crest and proximal tibia had a greater impact on functional improvement compared to PRP (P < 0.001 for WOMAC).

    “Similarly, Mormone et al. showed that BMAC obtained from the iliac crest and proximal tibia had a greater impact on pain reduction and functional improvement compared to PRP ( P &lt; 0.001 for both V AS and WOMAC). [20]”

    From Management of platelet-rich plasma and stem cells versus conventional treatments in musculoskeletal injury repair: A systematic review (2025) · cites this paper as [20]

    The Results section (“Primary outcome parameters: BMA vs PRP treatment”) reports significant WOMAC improvements within the treatment arms, but says the reductions did not differ significantly across arms. The Discussion (“Clinical outcomes”) likewise states that neither iliac-crest nor tibial treatment was superior to PRP at six months. Thus, P < 0.001 does not establish the claimed greater functional improvement compared with PRP. (LLM, conf=0.95)

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  • Mormone et al. showed that BMAC obtained from the iliac crest and proximal tibia had a greater impact on pain reduction compared to PRP (P < 0.001 for VAS).

    “Similarly, Mormone et al. showed that BMAC obtained from the iliac crest and proximal tibia had a greater impact on pain reduction and functional improvement compared to PRP ( P &lt; 0.001 for both V AS and WOMAC). [20]”

    From Management of platelet-rich plasma and stem cells versus conventional treatments in musculoskeletal injury repair: A systematic review (2025) · cites this paper as [20]

    The Results (Primary outcome parameters: BMA vs PRP treatment) report significant VAS and WOMAC improvements within the treatment arms, but no significant difference in reductions across the three arms. The cited P < 0.001 values are within-arm results, not evidence that iliac-crest or tibial BMA outperformed PRP. The Discussion (Clinical outcomes) likewise says the study did not find BMA superior to PRP. (LLM, conf=0.95)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Mormone et al. and Koh and Choi found that combining adipose-derived MSCs with PRP significantly improved joint function (as measured by the Lysholm and Tegner Activity Scale) and reduced pain compared to PRP alone (P < 0.001).

    “Mormone et al . and Koh and Choi found that combining adipose-derived MSCs with PRP significantly improved joint function (as measured by the Lysholm and Tegner Activity Scale) and reduced pain compared to PRP alone ( P &lt; 0.001). [20,22]”

    From Management of platelet-rich plasma and stem cells versus conventional treatments in musculoskeletal injury repair: A systematic review (2025) · cites this paper as [20]

    The Methods (Study design) describe bone-marrow aspirate from the iliac crest or tibia compared with PRP, not adipose-derived MSCs combined with PRP. The Discussion (Clinical outcomes) reports no significant differences in WOMAC function or VAS pain outcomes across the three arms at six months, contrary to the claimed superiority over PRP alone. (LLM, conf=0.90)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • In 45 patients with KL I-IV knee OA and VAS 8-10, BMAC from the iliac crest resulted in a VAS change of -5.0.

    “Mormone et al ., 2024 [20] | 45 with KL I-IV OA, VAS 8-10 | BMAC (iliac/tibia) | PRP | VAS: iliac Δ-5.0; WOMAC: tibia Δ-16. Iliac MSCs more abundant than tibia.”

    From Management of platelet-rich plasma and stem cells versus conventional treatments in musculoskeletal injury repair: A systematic review (2025) · cites this paper as [20]

    Table 2 (Results, Primary outcome parameters; page unavailable) reports a median VAS change of −5.00 in the iliac-crest arm. Table 1 shows 45 patients across three arms, but only 15 received iliac-crest treatment; its baseline VAS figures are group medians, not a requirement that all patients scored 8–10. The Methods describe the injected product as bone marrow aspirate (BMA), obtained without a concentration step, rather than BMAC. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In Mormone et al., WOMAC change for tibia BMAC was -16.

    “Mormone et al ., 2024 [20] | 45 with KL I-IV OA, VAS 8-10 | BMAC (iliac/tibia) | PRP | VAS: iliac Δ-5.0; WOMAC: tibia Δ-16. Iliac MSCs more abundant than tibia.”

    From Management of platelet-rich plasma and stem cells versus conventional treatments in musculoskeletal injury repair: A systematic review (2025) · cites this paper as [20]

    Results (Table 1; page unavailable) reports a median ΔWOMAC of −16.00 for the tibia arm. But Methods (Bone marrow aspiration technique; page unavailable) says patients received bone marrow aspirate (BMA) without a concentration step, not BMAC. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Authors
Mormone, E., Savastano, L., Rossi, G., Maruccia, F., Di Maggio, G., Sinisi, N. P., Sandri, M., Copetti, M., De Santis, E., Guerra, V., Biancofiore, G., Cisternino, C., Caradonna, E., Graziano, P., & Gorgoglione, F. L.
Affiliations
  • Casa Sollievo della Sofferenza (IT)
  • University of Brescia (IT)
  • Centro Diagnostico Italiano (IT)
  • Sapienza University of Rome (IT)
Corresponding author
Mormone, E.
ORCID
Venue
Journal of Translational Medicine
Publisher
Springer Science and Business Media LLC
Published
2024-12-04
Volume
22
Issue
1
Pages
1101-1101
ISSN
1479-5876 (ISSN-L)
DOI
10.1186/s12967-024-05924-y
PMC
PMC11616267
OpenAlex
W4405018956
Cited by
6
References
0
Citations by year
2026: 2 · 2025: 4
FWCI
1.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Translational Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by-nc-nd)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
  • Health Sciences › Dentistry › Periodontics › Periodontal Regeneration and Treatments
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
Keywords
knee osteoarthritis, bone marrow aspirate, posterior iliac crest, proximal tibia, mesenchymal stem cells, platelet-rich plasma, autologous cell therapy, regenerative cells, mononuclear cells, platelet count, WOMAC score, pain and function outcomes, Kellgren-Lawrence grade
MeSH terms
Aged, Anti-Inflammatory Agents, Female, Humans, Ilium, Male, Middle Aged, Osteoarthritis, Regeneration, Tibia, Treatment Outcome, Platelet-Rich Plasma, Mesenchymal Stem Cells

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