Original Article
Articular Cartilage Regeneration With Autologous Peripheral Blood Stem Cells Versus Hyaluronic Acid: A Randomized Controlled Trial

https://doi.org/10.1016/j.arthro.2012.12.008Get rights and content

Purpose

The purpose of this study was to compare histologic and magnetic resonance imaging (MRI) evaluation of articular cartilage regeneration in patients with chondral lesions treated by arthroscopic subchondral drilling followed by postoperative intra-articular injections of hyaluronic acid (HA) with and without peripheral blood stem cells (PBSC).

Methods

Fifty patients aged 18 to 50 years with International Cartilage Repair Society (ICRS) grade 3 and 4 lesions of the knee joint underwent arthroscopic subchondral drilling; 25 patients each were randomized to the control (HA) and the intervention (PBSC + HA) groups. Both groups received 5 weekly injections commencing 1 week after surgery. Three additional injections of either HA or PBSC + HA were given at weekly intervals 6 months after surgery. Subjective IKDC scores and MRI scans were obtained preoperatively and postoperatively at serial visits. We performed second-look arthroscopy and biopsy at 18 months on 16 patients in each group. We graded biopsy specimens using 14 components of the International Cartilage Repair Society Visual Assessment Scale II (ICRS II) and a total score was obtained. MRI scans at 18 months were assessed with a morphologic scoring system.

Results

The total ICRS II histologic scores for the control group averaged 957 and they averaged 1,066 for the intervention group (P = .022). On evaluation of the MRI morphologic scores, the control group averaged 8.5 and the intervention group averaged 9.9 (P = .013). The mean 24-month IKDC scores for the control and intervention groups were 71.1 and 74.8, respectively (P = .844). One patient was lost to follow-up. There were no notable adverse events.

Conclusions

After arthroscopic subchondral drilling into grade 3 and 4 chondral lesions, postoperative intra-articular injections of autologous PBSC in combination with HA resulted in an improvement of the quality of articular cartilage repair over the same treatment without PBSC, as shown by histologic and MRI evaluation.

Level of Evidence

Level II, randomized controlled trial (RCT).

Section snippets

Methods

Institutional Review Board approval was obtained from the Medical Ethics Committee at Universiti Putra Malaysia. This trial was registered under clinicaltrial.gov (NCT01076673).

A sample-sized study was performed before initiation of the trial based on a cohort study involving standard marrow stimulation and retrospective review of pilot data.15 Based on subjective International Knee Documentation Committee (IKDC) clinical scores, the minimum recruitment quota for each group to achieve the

Group Comparison

Demographics of the study participants are presented in Table 2. One patient in the control group was lost to follow-up. There was a significant difference in the age of the subjects in the 2 groups. The average age of the control group was 42 years and the average age of the intervention group was 38 years (P = .031).

Subjective IKDC Scores

At the 24-month time point, the average subjective IKDC score for the control group was 71.1 and it was 74.8 for the intervention group. The Student t test evaluation produced P =

Discussion

The results of this RCT evaluating postoperative intra-articular injections of PBSC and HA after arthroscopic subchondral drilling showed a significant statistical improvement in histologic and MRI scores. This confirmed our hypothesis that after arthroscopic subchondral drilling, postoperative intra-articular injections of autologous PBSC in combination with HA can improve the quality of articular cartilage repair compared with the injections without PBSC.

In assessing the results of articular

Conclusions

After arthroscopic subchondral drilling into grade 3 and 4 chondral lesions, postoperative intra-articular injections of autologous PBSC in combination with HA resulted in an improvement of the quality of articular cartilage repair over the same treatment without PBSC, as shown by histologic and MRI evaluation.

Acknowledgment

The authors thank Klinsel Sdn Bhd for monitoring this trial and the Ministry of Science, Technology and Innovation (MOSTI) Technofund (TF0409B104), Malaysia for funding this project in collaboration with Inno Bio Ventures Sdn Bhd and Faculty of Medicine, Universiti Putra Malaysia. In addition, they appreciatively acknowledge Dr. Sharon W.S. Chen (Info Analytic) for statistical evaluation, Dr. Norhafizah Mohtarrudin (Department of Pathology, Universiti Putra Malaysia) for histologic evaluation

References (34)

  • S. Civriz Bozdag et al.

    Older age and capacity of colony forming unit in autologous peripheral derived hematopoietic cells

    Transfusion Apheresis Sci

    (2012)
  • R.A. Magnussen et al.

    Treatment of focal articular cartilage defects in the knee: A systematic review

    Clin Orthop Relat Res

    (2008)
  • R.F. LaPrade et al.

    CS Carlson. Histologic and immunohistochemical characteristics of failed articular cartilage resurfacing procedures for osteochondritis of the knee: A case series

    Am J Sports Med

    (2008)
  • K. Mithoefer et al.

    The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study

    J Bone Joint Surg Am

    (2005)
  • H. Koga et al.

    Mesenchymal stem cell-based therapy for cartilage repair: A review

    Knee Surg Sports Traumatol Arthrosc

    (2009)
  • A.M. Bhosale et al.

    Articular cartilage: Structure, injuries and review management

    Br Med Bull

    (2008)
  • T. Minas et al.

    Autologous chondrocyte implantation

    Am J Knee Surg

    (2000)
  • Cited by (210)

    • Mobilized Peripheral Blood Stem Cells are Pluripotent and Can Be Safely Harvested and Stored for Cartilage Repair

      2021, Arthroscopy - Journal of Arthroscopic and Related Surgery
      Citation Excerpt :

      The cell product remained free of bacterial contamination and retained pluripotent stem potential out to 2 years. Our findings are similar to previous preclinical and clinical studies regarding PBSCs.22-24 This study translates PBSCs closer to widespread adoption by validating multicenter reproducibility.

    View all citing articles on Scopus

    The authors report that they have no conflicts of interest in the authorship and publication of this article.

    View full text